#GENE HGNC ID ENTREZ GENE ID CONDITION INHERITANCE AGE GROUP ALLELIC CONDITIONS MANIFESTATION CATEGORIES INTERVENTION CATEGORIES COMMENTS INTERVENTION/RATIONALE REFERENCES A2M 7 2 Alpha-2-macroglobulin deficiency AD N/A N/A General General Variants have been implicated in pulmonary disease, but the evidence appears mixed The clinical consequences of variants are unclear 94459; 2475424; 1370808 A2ML1 23336 144568 Otitis media, susceptibility to AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may have increased susceptibility to otitis media, and awareness may allow awareness leading to prompt diagnosis and treatment of otitis media 26121085 A4GALT 18149 53947 Blood group, P1PK system BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 10993874 AAAS 13666 8086 Achalasia-addisonianism-alacrimia syndrome AR Pediatric Dermatologic; Endocrine; Gastrointestinal; Neurologic; Ophthalmologic Endocrine Surveillance and treatment/preventive measures (with substitution therapy) to avoid sequelae of adrenal insufficiency, including adrenal crisis, may be beneficial 78049; 6243664; 3565479; 1537368; 8006362; 7895750; 8757578; 11062474; 11159947; 11914417; 12429595; 12752575; 16264411; 16938764; 8628786; 19172511; 18172684; 20051279; 20200814; 20499090; 20447142; 21565631 AAGAB 25662 79719 Keratoderma, palmoplantar, punctate type IA AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23000146; 23064416 AARS1 20 16 Charcot-Marie-Tooth disease, axonal, type 2N; Epileptic encephalopathy, early infantile, 29 AD/AR N/A N/A Audiologic/Otolaryngologic; Neurologic General Charcot-Marie-Tooth disease, axonal, type 2N can include hearing loss, which is described as postlingual; For epileptic encephalopathy, as with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20045102; 22206013; 22009580; 22573628; 25817015 AARS2 21022 57505 Leukoencephalopathy, progressive, with ovarian failure AR Pediatric Allelic with Combined oxidative phosphorylation deficiency 8 (AR) Biochemical; Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Obstetric Obstetric Females may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired 21549344; 24808023; 25058219 AASS 17366 10157 Hyperlysinemia, type I AR N/A N/A Biochemical General Other than increased serum lysine, the evidence of a common phenotype is unclear, and there does not appear to be evidence that measures such as protein restriction or other metabolic treatments are effective Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14209691; 5796356; 5557172; 934735; 10775527; 23570448 ABAT 23 18 GABA-transaminase deficiency AR Pediatric Biochemical; Neurologic Biochemical The condition includes neonatal or early-onset neurologic sequelae, and medical management (with continuous flumazenil) has been described as beneficial in a patient with a milder phenotype 6148708; 4020531; 10407778; 27596361; 28411234 ABCA1 29 19 Hypoalphalipoproteinemia, primary, 1; Tangier disease AD/AR Pediatric Cardiovascular; Neurologic; Ophthalmologic Cardiovascular Early cardiovascular events are common (eg, myocardial infarctions due to atherosclerosis), and while specific medical therapy is not currently available, preventive measures to decrease additional contributory atherosclerotic risk factors, as well as surveillance to allow early diagnosis and treatment of cardiovascular manifestations, may be beneficial 14162531; 5831900; 4165386; 4165172; 198431; 190272; 194920; 195100; 75948; 7406376; 4082916; 3677505; 3799433; 3314502; 8432861; 7627690; 10431237; 10431236; 10525055; 9888879; 10533863; 16343506; 10535983; 10431238; 11086027; 11476965; 12084722; 12111371; 12111381; 12702168; 14742612; 16343506; 18955690; 19723515; 22179783; 22913675; 23430904 ABCA12 14637 26154 Ichthyosis, congenital, autosomal recessive 4B; Ichthyosis, lamellar, type 2 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8204475; 12208260; 12915478; 16007253; 15756637; 16902423; 21339420; 21729033; 22257947 ABCA2 32 20 Intellectual developmental disorder with poor growth and with or without seizures or ataxia AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29302074; 30237576; 31047799 ABCA3 33 21 Surfactant metabolism dysfunction, pulmonary, 3 AR Pediatric Pulmonary Pulmonary Individuals may present in infancy with severe respiratory insufficiency (a presentation in early childhood ascribed to a heterozygous variant has also beeen described), and diagnosis has important therapeutic implications, as BMT can be effective; Lung transplant may be beneficial in some individuals 15044640; 15976379; 15819986; 15985750; 17719949; 22337229; 22304854; 23166334 ABCA4 34 24 Cone-rod dystrophy 3; Retinitis pigmentosa 19; Stargardt disease 1; Retinal dystrophy, early-onset severe; Fundus flavimaculatus; Macular degeneration, age-related, 2 AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9054934; 9466990; 9425888; 9781034; 10396622; 10442900; 10874631; 10396622; 11818392; 12515255; 12796258; 16896346; 16682602; 11385708; 21510770; 21786275; 22229821; 22312191; 22328824; 22395892; 22661473; 22863181; 23096905 ABCA5 35 23461 Hypertrichosis terminalis, generalized, with or without gingival hyperplasia AR N/A N/A Craniofacial; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24831815 ABCB1 40 5243 Colchicine metabolism, association with AD Pediatric General Pharmacogenomic Selection and dosing of medications (eg,colchicine) may be affected by the presence of variants 7188928; 7129432; 17259950; 18973929; 21851199 ABCB11 42 8647 Cholestasis, progressive familial intrahepatic 2 AR Pediatric Allelic with Cholestasis, benign recurrent intrahepatic, 2 (AR) Gastrointestinal; Oncologic Gastrointestinal; Oncologic The condition may involve multiple interacting variants In severe forms, specific nutritional care may be beneficial (eg, including specific vitamin E supplementation); Individuals are at high risk for hepatocellular carcinoma early in life, and surveillance and early treatment may be beneficial; Recurrence after liver transplant may benefit from immunosuppresive treatment; Liver transplant may be indicated 9806540; 10579978; 15300568; 16039748; 16871584; 20301474; 19797282; 21055686; 21766090; 21219577; 22675952 ABCB4 45 5244 Cholestasis, progressive familial intrahepatic 3; Low phospholipid-associated cholelithiasis 1; Cholestasis, oral contraceptives induced; Cholestasis, familial intrahepatic, of pregnancy; Gallbladder disease 1 AD/AR Pediatric Gastrointestinal Gastrointestinal; Obstetric; Pharmacogenomic Heterozygous variants reported in Cholestasis, progressive familial intrahepatic 3 are associated with other related conditions such as Intrahepatic cholestasis of pregnancy Medical treatment (eg, with ursodeoxycholine) may be beneficial, though in some forms, liver transplantation has been described as necessary; Medications (eg, OCPs) may lead to adverse reactions; In pregnancy, the condition can cause severe sequelae (including death) in the fetus, as well as adverse maternal health outcomes, and precautions, including early delivery, may be beneficial 8666348; 9049190; 9419367; 9923886; 10767346; 11313315; 11313316; 15203080; 17726488; 17414143; 18482588; 19584064; 20887599; 20537830; 21310683; 21119540; 21989363 ABCB6 47 10058 Pseudohyperkalemia, familial, 2, due to red cell leak; Blood group, Langereis system AD/BG Pediatric Allelic with Dyschromatosis universalis hereditaria (AD); Microphthalmia, isolated, with coloboma 7 (AD) Dermatologic; Hematologic; Ophthalmologic Hematologic Variants related to Familial pseudohyperkalemia may be important related to transfusion management; Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 5790273; 22246506; 22226084; 23180570; 23519333; 24947683 ABCB7 48 22 Anemia, sideroblastic, and spinocerebellar ataxia XL N/A N/A Hematologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4045952; 10196363; 20301496; 22398176 ABCC1 51 4363 Deafness, autosomal dominant 77 AD N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31273342 ABCC11 14639 85320 Apocrine gland secretion, variation in AR N/A N/A Dermatologic General The clinical relevance is unclear 16444273; 19710689 ABCC2 53 1244 Dubin-Johnson syndrome AD/AR N/A N/A Gastrointestinal General Heterozygotes may display manifestations; The presence of variants may have pharmacogenomic implications Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13193360; 5926936; 5532959; 520367; 2035335; 8621134; 9425227; 16952291; 16863439; 16549534; 19881259; 21044052; 22955427; 23007012; 23069858; 23115734 ABCC6 57 368 Pseudoxanthoma elasticum (including Pseudoxanthoma elasticum, forme fruste) AD/AR/Digenic Pediatric Allelic with Generalized calcification of infancy, 2 (AR) Cardiovascular; Dermatologic; Hematologic; Ophthalmologic Cardiovascular; Hematologic; Ophthalmologic In "recessive" forms, heterozygotes may have mild manifestations; Digenic inheritance (with GGCX) has been reported Preventive measures (eg, weight control, avoidance of smoking, and medical management of hypertension and hypercholesterolemia) related to cardiovascular risk factors may be beneficial by decreasing contributory factors related to atherosclerosis; Awareness may allow surveillance for and early detection and treatment of cardiovascular (eg, surgical interventions related to vascular disease) and hematologic manifestations (eg, interventions related to GI bleeding); Standard treatment for macular degeneration (including intraocular injection of anti-angiogenic drugs) may be beneficial, and awareness of ophthalmologic aspects may allow early detection and treatment; Circumstances such as contact sports and the use of medications that increase the risk of GI bleeding should be avoided 14068068; 3652487; 3342167; 2012127; 1600795; 8413390; 10619263; 10835643; 10835642; 10811882; 11209132; 15098239; 16086317; 18157818; 18800149; 19298904; 20034067; 20075945; 20301292; 21210805; 21386758; 21671388; 22209248; 23675997; 23746223; 23935882; 23968982; 23978319; 24008425; 24749718 ABCC8 59 6833 Diabetes mellitus, transient neonatal, 2; Diabetes, permanent neonatal 3; Hyperinsulinemic hypoglycemia, familial, 1; Hypoglycemia, leucine-induced AD/AR Pediatric Endocrine Endocrine Hyperinsulinemic hypoglycemia, familial, 1 inheritance may involve imprinting Prompt treatment (eg, of ketoacidosis and dehydration) can avoid morbidity; Individuals with neonatal diabetes mellitus may respond well to sulfonylurea treatment; Non-neonatally affected individuals may respond to diazoxide; Individuals with leucine-induced hypoglycemia may have episodes triggered by high-protein (high leucine) feedings, and may respond to diazoxide 7847376; 7716548; 923011; 8751851; 9727845; 10426386; 10322395; 11808881; 10334322; 1018078; 12559865; 12941782; 15356046; 15579781; 16885549; 16882742; 16613899; 8596924; 19254908; 20301620; 21716120; 23273570 ABCC9 60 10060 Cardiomyopathy, dilated, 1O; Atrial fibrillation, familial 12; Cantu syndrome AD Pediatric Cardiovascular; Dermatologic; Musculoskeletal Cardiovascular Though manifestations have been described in adults, surveillance and interventions should likely begin in the pediatric period Surveillance for related cardiac complications, which have been reported to include cardiomyopathy and arrhythmias, may allow early medical intervention, decreasing morbidity and mortality; Cantu syndrome, which may be clinically recognizable,can include cardiovascular malformations that would benefit from surveillance/intervention similar to other ABCC9-related disorders 15034580; 16563363; 17245405; 22610116; 22608503 ABCD1 61 215 Adrenoleukodystrophy XL Pediatric Biochemical; Endocrine; Neurologic Biochemical For individuals with adrenal insufficiency, corticosteroid treatment is indicated; In asymptomatic individuals with ALD, medical treatment (eg, with oleic and erucic acids) may be beneficial in combination with dietary measures, though the benefit of such treatment in other affected individuals, such as symptomatic individuals, may not warrant such treatment; BMT/HSCT has been reported as effective if performed early 169765; 61263; 965973; 200861; 200862; 218453; 7438498; 7436359; 6299222; 7202134; 6280106; 6387532; 2682348; 2309698; 7904210; 8094785; 8338333; 8441467; 7849723; 8040304; 7581394; 7825602; 8566952; 8636252; 9062496; 9183487; 10073906; 9894883; 11748843; 11085690; 11204280; 11916318; 11220738; 12210797; 12486501; 12913200; 15073029; 15812458; 16240348; 15668429; 16305618; 16380594; 16009761; 16313334; 17372139; 17353371; 18759549; 19892975; 20301491 ABCD3 67 5825 Biochemical; Gastrointestinal; Neurologic AR Pediatric Biochemical; Craniofacial; Gastrointestinal; Neurologic Gastrointestinal Early interventions, such as with bile replacement therapy, may be beneficial, though liver transplant may be necessary 1301993; 9199576; 10447258; 17092750; 25168382 ABCD4 68 5826 Methylmalonic aciduria and homocystinuria, cblJ type AR Pediatric Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Neurologic Allergy/Immunology/Infectious; Biochemical; Cardiovascular Administration of hydroxocobalamin/methylcobalamin has been described as beneficial; Due to infectious risks, administration of G-CSF has been described, and early and aggressive treatment of infections may be benefiical; Surveillance for cardiovascular manifestations may allow early management 22922874; 23141461 ABCG2 74 9429 Blood group, junior system BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 567888; 18522708; 20890084; 22246505; 22246507 ABCG5 13886 64240 Sitosterolemia 2 AR Pediatric Biochemical; Cardiovascular; Hematologic Biochemical; Cardiovascular In some individuals, medical (eg, with bile acid resins/lipid-lowering agents) and dietary (eg, with cholesterol and plant fat restriction) treatment may be beneficial for some parameters, and may, along with preventive measures related to cardiovascular manifestations, reduce morbidity and mortality 11099417; 11138003; 12840092; 16029460; 16472606; 17018391; 17785700; 17976197; 19111681; 20521169; 20543520; 20719861; 21576934; 24166850 ABCG8 13887 64241 Sitosterolemia 1 AR Pediatric Biochemical; Cardiovascular; Hematologic Biochemical; Cardiovascular In some individuals, medical (eg, with bile acid resins/lipid-lowering agents) and dietary (eg, with cholesterol and plant fat restriction) treatment may be beneficial for some parameters, and may, along with preventive measures related to cardiovascular manifestations, reduce morbidity and mortality 11099417; 12840092; 16029460; 15996216 ABHD12 15868 26090 Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract AR N/A N/A Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19005174; 20797687; 22938382; 24697911 ABHD5 21396 51099 Chanarin-Dorfman syndrome AR N/A N/A Biochemical; Dermatologic General Manifestations can include severe hepatic sequelae Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10712205; 11590543; 21757733; 22245374; 22373837; 25468645 ABL1 76 25 Congenital heart defects and skeletal malformations syndrome AD Adult Cardiovascular; Musculoskeletal Cardiovascular The condition can include adult-onset aortic root dilation, and awareness may allow early identification and management 28288113 ABO 79 28 Blood group, ABO system BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 4014172; 2647864; 2333095; 1303212; 1572640; 8075282; 7772867; 9099833; 11520811; 12014997; 12829588; 17959777 ACAD8 87 27034 Isobutyryl-CoA dehydrogenase deficiency AR Pediatric Biochemical; Cardiovascular; Hematologic; Musculoskeletal; Neurologic Biochemical Metabolic precautions may be beneficial to prevent and treat acute decompensation; Medical treatment (eg, with oral L-carnitine) has been reported as allowing growth catch-up and normalization of cardiac status 9889013; 12359132; 17304052; 16857760; 17924841; 21290185; 22241096 ACAD9 21497 28976 Mitochondrial complex I deficiency, nuclear type 20 AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic Biochemical Individuals may present early in life with findings including neurologic abnormalities, cardiomyopathy, and lactic acidosis, and early institution of medical treatment (eg, with riboflavin) has been reported as leading to marked decreases in morbidity/mortality 17564966; 21057504; 20929961; 21057504; 22499348; 25721401 ACADM 89 34 Acyl-CoA dehydrogenase, medium chain, deficiency of AR Pediatric Biochemical; Musculoskeletal; Neurologic Biochemical Dietary treatment (eg, with frequent feedings in infancy, and low-fat diet for toddlers, as well as bedtime administration of uncooked cornstarch to avoid overnight hypoglycemia); In order to avoid/treat catabolism, simple oral (or IV if necessary) carbohydrates can be effective; Fasting should be avoided, as should infant formulas whose primary fat source is medium-chain triglycerides 947635; 6402754; 6857268; 6646897; 3462713; 3944676; 3822638; 2502671; 2393404; 1361190; 8120710; 7603790; 9158144; 11349232; 11524729; 11409868; 15915086; 15832312; 19780764; 20923556; 20434380; 21239873; 20301597; 23574375 ACADS 90 35 Acyl-CoA dehydrogenase, short-chain, deficiency of AR Pediatric Biochemical;Musculoskeletal; Neurologic Biochemical Clinical manifestations range from infantile acute acidosis and muscle weakness to chronic adult myopathy, and in the infantile forms, medical/dietary therapy (eg, IV glucose/carnitine in the initial phase, and low-fat, diet with MCT oil and carnitine and riboflavin, as well as avoidance of fasting) can be effective 3571488; 3335634; 2808706; 7776094; 9266373; 9499414; 9578969; 9932958; 11134486; 11524729; 18523805; 18054510; 20376488; 20429031; 21325261; 21500142 ACADSB 91 36 2-methylbutyryl-CoA dehydrogenase deficiency AR N/A N/A Biochemical General The clinical relevance of the condition is unclear, though some have stated that special attention may be necessary in situations involving potential metabolic decompensation 10832746; 12837870; 16317551; 17883863; 17945527; 20547083; 21290185 ACADVL 92 37 Acyl-CoA dehydrogenase, very long chain, deficiency of AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Renal Biochemical; Cardiovascular; Musculoskeletal; Renal There are multiple forms of VLCAD deficiency, and interventions depend on the form (typical medical/dietary therapy includes IV glucose/carnitine in initial phases, as well as low-fat, diet with MCT oil and carnitine, and avoidance of fasting); In the severe, early-onset form, medical treatment of cardiomyopathy may be beneficial; In thechildhood onset form, treatment of hypoketotic hypoglycemia may be beneficial; In the adult-onset, myopathic form, preventive measures related to with irhabdomyolysis, and myoglobinuria after exercise or fasting may be beneficial 4022672; 2059253; 2000272; 1527994; 8422439; 8356011; 8145917; 7668252; 7769092; 7479827; 8739959; 8554073; 9709714; 9877038; 9546340; 9973285; 10077518; 10790204; 11158518; 11524729; 15210884; 17636072; 19327992; 19208414; 19399638; 19452263; 21531094; 21814341; 22847164; 23480858 ACAN 319 176 Spondyloepimetaphyseal dysplasia, aggrecan type; Spondyloepiphyseal dysplasia, Kimberley type; Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans AD N/A Allelic with Spondyloepimetaphyseal dysplasia, aggrecan type (AR); Spondyloepiphyseal dysplasia, Kimberley type (AD) Craniofacial; Endocrine; Musculoskeletal Endocrine Individuals have been described as benefiting from growth hormone treatment 14353963; 14216462; 7331787; 3968094; 1978986; 16080123; 18226555; 19110214; 20137779; 27710243; 28331218; 30124491 ACAT1 93 38 Alpha-methylacetoacetic aciduria AR Pediatric Biochemical; Neurologic Biochemical Individuals typically present with hypoglycemic or hyperglycemic ketoacidosis due to fasting, illnesses, and dietary changes (eg, increased protein), which can result in severe neurologic sequelae or death, and diagnosis can allow dietary and medical management (eg, protein restriction and l-carnitine supplementation) to avoid acute crises and subsequent sequelae 4143539; 4690360; 4812006; 8103405; 8103405; 9700610; 15877211; 17236799; 18511318; 16950638; 20046049; 20157782; 21669895; 23430882; 23920042; 23958592 ACBD5 23338 91452 Retinal dystrophy with leukodystrophy AR N/A N/A Biochemical; Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23105016; 27799409 ACD 25070 65057 Dyskeratosis congenita, autosomal dominant 6; Dyskeratosis congenita, autosomal recessive 7 AD/AR Pediatric Allergy/Immunology/Infectious; Hematologic; Oncologic; Neurologic Allergy/Immunology/Infectious; Hematologic; Oncologic Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; HSCT may be indicated due to manifestations including leukemia and bone marrow failure; Awareness of infectious risk may allow prompt diagnosis and treatment of infections 25205116; 25233904 ACE 2707 1636 Renal tubular dysgenesis AR Pediatric Allelic with ACE serum levels (AD) Endocrine; Renal Endocrine; Renal Individuals have been described with severe, early-onset renal and related sequelae, and vasopressin has been described as successfully treating refractory hypotension and anuria; Treatment of low aldosterone (with fludrocortisone) has been described as beneficial 2989970; 1976655; 1328889; 1386652; 8131299; 7909524; 8208911; 8314010; 8675669; 7593601; 9120002; 11076943; 11551873; 11956052; 12666117; 15381116; 15531537; 15277638; 16116425; 22095942; 25899979 ACER3 16066 55331 Leukodystrophy, progressive, early childhood-onset AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26792856 ACHE 108 43 Blood group, Yt system BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 8488842 ACKR1 4035 2532 Blood group, Duffy system BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 6386656; 8248172; 7663520; 7669660; 7705836; 8547665; 9886340; 9746760; 9731074; 10073905; 10570183; 20932074 ACKR3 23692 57007 Oculomotor-abducens synkinesis AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30372748 ACO2 118 50 Infantile cerebellar-retinal degeneration; Optic atrophy 9 AR N/A N/A Audiologic/Otolaryngologic; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22405087; 25351951; 31106992 ACOX1 119 51 Mitchell syndrome AD Pediatric Allelic with Peroxisomal acyl-CoA oxidase deficiency (AR) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Craniofacial; Neurologic; Ophthalmologic Allergy/Immunology/Infectious The condition has been described as manifesting with episodic demyelination, sensorimotor polyneuropathy, and hearing loss, and early diagnosis may allow medical management (eg, immunomodulatory and related treatments have been reported to show some clinical benefits in individuals) 2894756; 8040306; 8279468; 11815777; 17458872; 18536048; 32169171 ACOX2 120 8309 Bile acid synthesis defect, congenital, 6 AR Pediatric Gastrointestinal Gastrointestinal Individuals have been described with hepatic dysfunction, and avoidance of hepatotoxic agents and medical management (eg, with cholestyramine) has been described as beneficial 27647924; 27884763 ACP4 14376 93650 Amelogenesis imperfecta, type IJ AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27843125 ACP5 124 54 Spondyloenchondrodysplasia with immune dysregulation AR Pediatric Allergy/Immunology/Infectious; Endocrine; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Clinically recognizable non-immune features may not be recognized early; The condition can affect multiple organ systems for which early knowledge of disease could be beneficial, including infectious and autoimmune sequelae Individuals may have immune deficiency, and a variety of infections have been reported, including pneunomia, upper respiratory infections, and severe varicella infections, and thus antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals may also have a variety of autoimmune manifestations, including hypothyroidism, and treatment may be beneficial 12786759; 17497723; 17163538; 18924170; 21217755; 21217752; 26854080; 26951490 ACSF3 27288 197322 Combined malonic and methylmalonic aciduria AR Pediatric Biochemical; Neurologic Biochemical Although the optimal treatment (as well as the requirement thereof) is currently unclear, additional monitoring may be warranted to determine whether medical management would be beneficial 9700595; 21785126; 21841779; 30740739 ACSL4 3571 2182 Mental retardation, X-linked 63 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10854107; 11889465; 12525535 ACTA1 129 58 Myopathy, congenital, with fiber-type disproportion 1; Nemaline myopathy 3; Myopathy, scapuloperoneal AD/AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4952447; 9185179; 10508519; 11333380; 15520409; 15468086; 16427282; 19553116; 22442437; 25938801 ACTA2 130 59 Moyamoya disease 5; Multisystemic smooth muscle dysfunction syndrome; Aortic aneurysm, familial thoracic 6 AD Pediatric Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular Surveillance for cardiovascular complications (eg, aortic aneurysm), as well as related preventive measures to help control contributory factors may reduce morbidity and mortality by allowing early diagnosis and treatment; There has been a reported increased risk of aortic dissection with minimal aortic dilatation during the pregnancies of affected women, and awareness may allow monitoring and management 17994018; 19409525; 22051261; 22302747; 24243736; 29300374 ACTB 132 60 Baraitser-Winter syndrome 1 AD Pediatric Allelic with Dystonia, juvenile-onset (AD) Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal Audiologic/Otolaryngologic Baraitser-Winter syndrome 1 can include hearing impairment as well as multiple congenital anomalies Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 3351890; 12325076; 16685646; 22366783; 23649928; 25052316; 30921093 ACTC1 143 70 Cardiomyopathy, dilated, 1R; Cardiomyopathy, familial hypertrophic 11; Atrial septal defect 5 AD Pediatric Cardiovascular Cardiovascular Different ACTC1-related disorders have been associated with pediatric or adult-onset disease, but surveillance beginning in the pediatric period may be beneficial Surveillance (including with electrocardiogram and echocardiogram), preventive measures, and medical management of cardiomyopathies may be helpful to help decrease morbidity and mortality 9563954; 10330430; 10966831; 6267253; 17611253; 18467357; 18506004; 17947298; 20301486; 20301725; 21239446 ACTG1 144 71 Baraitser-Winter syndrome 2 AD Pediatric Allelic with Deafness, autosomal dominant 20/26 (AD) Audiologic/Otolaryngologic;Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal Audiologic/Otolaryngologic Baraitser-Winter syndrome 2 can include hearing impairment as well as multiple congenital anomalies Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 5654493; 3351890; 12519370; 14684684; 13680526; 16773128; 19477959; 22366783; 25052316 ACTG2 145 72 Visceral myopathy 1 AD Pediatric Gastrointestinal; Genitourinary; Neurologic Gastrointestinal Individuals have been described as presenting with findings including chronic intestinal pseudo-obstruction and related abdominal signs and symptoms, and genetic knowledge may help avoid unnecessary surgery (medical management has been described as at least partially effective in some individuals); TPN and urinary catheterization may be beneficial 19098683; 24676022; 24777424 ACTL6B 160 51412 Intellectual developmental disorder with severe speech and ambulation defects; Developmental and epileptic encephalopathy 76 AD/AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26539891; 30237576; 30656450; 31031012; 31134736 ACTL9 28494 284382 Spermatogenic failure 53 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33626338 ACTN1 163 87 Bleeding disorder, platelet-type, 15 AD N/A N/A Hematologic General Individuals have been described with no or mild bleeding tendency, and it is unclear that genetic diagnosis would enable interventions or differences in management Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23434115 ACTN2 164 88 Cardiomyopathy, dilated, 1AA, with or without left ventricular noncompaction; Cardiomyopathy, hypertrophic 23, with or without left ventricular noncompaction; Myopathy, congenital with structured cores and Z-line abnormalities AD Pediatric Allelic with Myopathy, distal, 6, adult onset (AD) Cardiovascular; Musculoskeletal Cardiovascular Preventive measures and medical management of cardiomyopathy may be helpful to help decrease morbidity and mortality 14567970; 20301486; 20022194; 20301725; 25173926; 25224718; 30701273; 30900782 ACTN3 165 89 ACTN3 deficiency AR N/A N/A Musculoskeletal General The clinical relevance is unclear 10192379; 11845199; 12879365; 15886711; 17033684; 17627799; 17828264 ACTN4 166 81 Focal segmental glomerulosclerosis 1 AD Pediatric Renal Renal The condition can involve renal failure, and early diagnosis may enable management considerations; Renal transplant has been described 10700177; 15208719; 19142020; 19357256; 19666657 ACVR1 171 90 Fibrodysplasia ossificans progressiva AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8758048; 17077940; 16642017; 17351709; 18830232; 19330033; 24259422 ACVR2B 174 93 Heterotaxy, visceral, 4, autosomal AD N/A N/A Cardiovascular; Gastrointestinal; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9916847 ACVRL1 175 94 Telangiectasia, hereditary hemorrhagic, type 2 AD Pediatric Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Pulmonary Cardiovascular; Gastrointestinal; Hematologic; Obstetric; Pharmacogenomic; Pulmonary There are a number of surveillance/preventive/treatment based measures; These include: epistaxis treatment with humidification, lubricants, hormone therapy, anti-fibrinolytic agents, ablation, surgery, etc.; GI bleeding: iron replacement, hormonal or anti-fibrinolytic medication, surgery, etc.; Pulmonary AVM: catheter occlusion, and preventive measures such as antibiotic prophylaxis; symptomatic cerebral AVMs: surgery/embolotherapy, etc; Severe hepatic AVMs: liver transplantation if medical management fails; Specific pregnancy-related screening may be indicated; Anemia: Iron replacement or transfusion; Avoidance of certain activities and use of anticoagulant and anti-inflammatory agents (including aspirin) in the case of significant bleeding; For PAH, medical therapy (eg, prostanoids, endothelin receptor antagonists, etc.) may be beneficial, but lung transplantation may be indicated 5037289; 3186989; 8640225; 10946360; 9354504; 11170071; 11484689; 14684682; 16470787; 16155196; 6542389; 17786384; 18498373; 18831062; 18312453; 19439755; 20056902; 20301525 ACY1 177 95 Aminoacylase 1 deficiency AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16274666; 16465618; 17562838; 20480396; 24117009 ADA 186 100 Severe combined immunodeficiency due to adenosine deaminase deficiency AR Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic Variants may also contribute to Partial ADA deficiency; Gene therapy may be available, though largely on an experimental basis Enzyme treatment (with PEG-ADA) is beneficial; Antiinfectious prophylaxis and early and aggressive treatment of infections are indicated; BMT has been described in many individuals; Surveillance for certain neoplasms may be beneficial 4117384; 46025; 1089883; 978319; 18618; 980079; 477037; 38963; 7436484; 6863546; 3781559; 3946419; 3007108; 3475710; 3807953; 3260944; 2783588; 2166947; 8227344; 8099155; 8051429; 1974554; 8023852; 8120281; 9108404; 10021471; 12089448; 14499267; 16905365; 19638621; 21725047; 21865538; 22153773; 22348551; 22447032; 22791287; 22805442; 22968453; 23118212; 23895897 ADA2 1839 51816 Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome; Sneddon syndrome AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Dermatologic Allergy/Immunology/Infectious Among other manifestations, individuals have been described as presenting with hypogammaglobulinemia, as well as recurrent bacterial and viral infections, and immunosuppressive treatment has been described as beneficial, though other manifestations have been described as recalcitrant to these types of therapies; Medical management (eg, with TNF inhibitor) has been described as beneficial. 12804991; 24552284; 24552285; 25075844; 25075847 ADAM10 188 102 Reticulate acropigmentation of Kitamura AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23666529 ADAM17 195 6868 Inflammatory skin and bowel disease, neonatal 1 AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal Allergy/Immunology/Infectious; Cardiovascular Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals may also have cardiovascular manifestations, and surveillance may allow beneficial interventions 22010916 ADAM22 201 53616 Developmental and epileptic encephalopathy 61 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27066583 ADAM9 216 8754 Cone-rod dystrophy 9 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11581183; 19409519; 25091951 ADAMTS10 13201 81794 Weill-Marchesani syndrome 1 AR Pediatric Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular; Ophthalmologic Individuals can have cardiac anomalies, including long QTc, and awareness may allow for preventive/medical management, which may decrease morbidity and mortality; As the condition can include glaucoma, surveillance can allow early interventions that may potentially be beneficial related to preservation of visual status 11941487; 14598350; 15368195; 17663475 ADAMTS13 1366 11093 Thrombotic thrombocytopenic purpura, hereditary (Schulman-Upshaw syndrome) AR Pediatric Hematologic; Neurologic; Renal Hematologic; Obstetric Administration of plasma can be beneficial; Specific treatment in pregnancy may be beneficial 14443744; 651994; 7290149; 11530798; 11586351; 12181489; 12576319; 12637323; 19055667 ADAMTS17 17109 170691 Weill-Marchesan syndrome 4 AR Pediatric Musculoskeletal; Ophthalmologic Ophthalmologic; Pharmacogenomic Individuals may be at risk of glaucoma, and surveillance may allow early management and preventive measures; Agents that may contribute to glaucoma should be avoided 19836009; 20375329; 22486325 ADAMTS18 17110 170692 Microcornea, myopic chorioretinal atrophy, and telecanthus AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21862674; 22686506; 23356391; 23818446 ADAMTS2 218 9509 Ehlers-Danlos syndrome, dermatosparaxis type AR Pediatric Craniofacial; Dermatologic; Musculoskeletal; Obstetric Obstetric Individuals may be prone to injuries (especially during delivery, as multiple congenital skull fractures and intracranial hemorrhage have been reported), and knowledge may allow delivery-based interventions to decrease related morbidity and mortality 1303238; 8215497; 7735500; 10417273; 15373769; 15389701; 18973246 ADAMTS3 219 9508 Hennekam lymphangiectasia-lymphedema syndrome 3 AR Pediatric Craniofacial; Gastrointestinal Endocrine; Gastrointestinal The condition can include manifestations such as protein-losing enteropathy, and awareness may allow prompt diagnosis and management (such as nutrition via feeding tube), Endocrine manifestations such as growth hormone deficiency have been observed, and awareness may allow prompt recognition and treatment 28985353 ADAMTSL2 14631 9719 Geleophysic dysplasia 1 AR Pediatric Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal Cardiovascular The disorder may frequently be clinically recognizable, but individuals can have cardiovascular manifestations such as progressive cardiac valve thickening necessitating surgical interventions very early in childhood, and early diagnosis may be beneficial to allow early treatment 18677313; 21415077; 21683322; 20301776 ADAMTSL4 19706 54507 Ectopia lentis et pupillae; Ectopia lentis 2, isolated, autosomal recessive AR Pediatric Ophthalmologic Ophthalmologic; Pharmacogenomic Although management related to some manifestations may be made through clinical observations (eg, related to amblyopia), surveillance related to intraocular pressure monitoring may be beneficial to allow prompt interventions; preventive measures (eg, related to contact sports) may be beneficial; Agents that may contribute to glaucoma should be avoided 2377351; 19200529; 20702823; 21051722; 22736615; 2338190 ADAR 225 103 Dyschromatosis symmetrica hereditaria; Aicardi-Goutieres syndrome 6 AD/AR N/A N/A Dermatologic; Hematologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12916015; 12713580; 23001123; 24262145; 25243380 ADARB1 226 104 Neurodevelopmental disorder with hypotonia, microcephaly, and seizures AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32220291 ADAT3 25151 113179 Mental retardation, autosomal recessive 36 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23620220 ADCY1 232 107 Deafness, autosomal dominant 44 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 15583425; 24482543 ADCY10 21285 55811 Hypercalciuria, absorptive, 2 AD N/A N/A Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11932268 ADCY3 234 109 Obesity, susceptibility to, 19 AR N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29311636; 29311637 ADCY5 236 111 Dyskinesia, familial, with facial myokymia AD Adult Cardiovascular; Neurologic Cardiovascular In addition to neurologic manifestations, individuals have been described with dilated cardiomyopathy and congestive heart failure, and awareness may allow surveillance (eg, with echocardiography), and early management 11310626; 22782511; 24700542 ADCY6 237 112 Lethal congenital contracture syndrome 8 AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24319099 ADD3 245 120 Cerebral palsy, spastic quadriplegic, 3 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23836506 ADGRE2 3337 30817 Vibratory urticaria AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7294069; 26841242 ADGRG1 4512 9289 Polymicrogyria, bilateral frontoparietal; Polymicrogyria, bilateral perisylvian AR N/A N/A Neurologic General Variants involving cis-regulatory elements have additionally been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15044805; 20929962; 21349848; 21723461; 23274687; 24531968 ADGRG2 4516 10149 Vas deferens, congenital bilateral aplasia of, X-linked XL N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27476656 ADGRG6 13841 57211 Lethal congenital contracture syndrome 9 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26004201 ADGRV1 17416 84059 Usher syndrome, type IIC AR/Digenic Pediatric Allelic with Febrile seizures, familial, 4 (AD) Audiologic/Otolaryngologic; Neurologic; Ophthalmologic Audiologic/Otolaryngologic Digenic inheritance has been described (with PDZD7) Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12402266; 14740321; 16273391;19357116; 18854872; 0440071; 21174530 ADH5 253 128 AMED syndrome, digenic Digenic Pediatric Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic Hematologic; Oncologic The condition is described as being caused by bi-allelic variants in ADH5 and a specific allele in ALDH2 The condition can include bone marrow failure as well as predisposition to malignancy, and awareness may allow early diagnosis and management of these manifestations 33355142 ADK 257 132 Hypermethioninemia due to adenosine kinase deficiency AD N/A N/A Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Gastrointestinal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21963049 ADNP 15766 23394 Helsmoortel-van der Aa syndrome (Mental retardation, autosomal dominant 28) AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24531329; 25057125 ADPRS 21304 54936 Neurodegeneration, childhoo-onset, stress-induced, with variable ataxia and seizures AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30100084; 30401461 ADRA2B 282 151 Epilepsy, myoclonic, familial adult, 2 AD N/A N/A Neurologic General As with many disorders involving seizures, appropriate interventions may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24114805 ADRA2C 283 152 Beta-blocker response, association with AD Pediatric General Pharmacogenomic The presence of variants may influence medication choice (eg, in congestive heart failure) 17496726 ADRB1 285 153 Beta-blocker response, association with AD Pediatric Allelic with Short sleep, familial natural, 2 (AD) Neurologic Pharmacogenomic The presence of variants may influence medication choice (eg, in congestive heart failure) 10212248; 12197595; 12374873; 16844790; 17496726; 31473062 ADRB2 286 154 Beta-2-adrenoreceptor agonist, reduced response to AD Pediatric General Pharmacogenomic Selection of medications (eg, in asthma treatment) may be influenced by the presence of certain variants 8383511; 7706471; 9399966; 11306963; 11739457; 12030897; 12571262; 15284533; 15500895; 15867853; 16596417 ADSL 291 158 Adenylosuccinase deficiency AR N/A N/A Biochemical; Neurologic General As with many disorders involving seizures, appropriate interventions may be beneficial (eg, ketogenic diet has been reported as beneficial) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6150139; 3234432; 1405483; 1302001; 9266401; 9266351; 10090474; 10888601; 11042421; 12070256; 12833398; 17188615; 18524658; 18649008; 18830228; 20177786; 20933180; 22883297; 23055421; 23504561 ADSS1 20093 122622 Myopathy, distal, 5 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26506222; 28268051; 32331917; 32646962 AEBP1 303 165 Ehlers-Danlos syndrome, classic-like, 2 AR Pediatric Cardiovascular; Gastrointestinal; Genitourinary; Musculoskeletal Cardiovascular; Gastrointestinal The condition can include manifestations such as bowel rupture and cardiovascular complications including aortic root dilatation, and awareness may allow surveillance, preventative measures, and early management 27023906; 29606302 AFF2 3776 2334 Premature ovarian failure XL Pediatric Allelic with Intellectual developmental disorder, X-linked 109 (XL) Endocrine; Neurologic; Obstetric Obstetric Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency 8334699; 8023854; 7536393; 7783162; 8673085; 8651274; 9341861; 9475603; 10528856; 12605436; 19136466; 21739600 AFF3 6473 3899 KINSSHIP syndrome AD N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Pulmonary; Renal General Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency 31388108; 33961779 AFF4 17869 27125 Cognitive impairment, coarse facies, Heart defects, Obesity, Pulmonary involvement, Short stature, and skeletal dysplasia (CHOPS syndrome) AD N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25730767 AFG3L2 315 10939 Optic atrophy 12; Spinocerebellar ataxia 28; Spastic ataxia 5, autosomal recessive AD/AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16251216; 20725928; 20208537; 25401298; 32219868 AFP 317 174 AFP deficiency, congenital; Hereditary persistence of AFP AD/AR N/A N/A General General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1690155; 1379776; 7684942; 15280901; 18854864 AGA 318 175 Aspartylglucosaminuria AR N/A N/A Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4173687; 5512217; 6796777; 6883788; 3228136; 1904874; 1722323; 1703489; 1765378; 1756604; 1301945; 8405810; 8064811; 9427148; 9627765; 10353787; 11174635; 11796409; 12022293; 12366426; 15127757; 16218917; 23271757 AGBL1 26504 123624 Corneal dystrophy, Fuchs endothelial, 8 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24094747 AGBL5 26147 60509 Retinitis pigmentosa 75 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26355662; 26720455 AGK 21869 55750 Sengers syndrome AR Pediatric Allelic with Cataract 38 (AR) Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic Biochemical; Cardiovascular Individuals can have cardiomyopathy, and early diagnosis may benefit medical management; Avoidance of factors that may precipitate lactic acidosis may be beneficial 1168700; 3789054; 3560758; 3337009; 15168109; 16736096; 22415731; 22277967; 22284826; 23266196 AGL 321 178 Glycogen storage disease III AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic Biochemical; Pharmacogenomic Dietary measures (eg, high-protein diet with frequent feeding, including cornstarch) to maintain glucose levels is beneficial; Certain medications should be avoided or used with caution; Experimental treatment (eg, with synthetic ketone bodies) has been described as additionally beneficial; Liver transplantation has been described 5235982; 5285455; 288318; 6572629; 2792130; 2295969; 1293383; 1632441; 8253364; 8273986; 8755644; 8990006; 10472540; 10982190; 10655153; 11977176; 17047887; 18541889; 18924225; 19834502; 21073127; 21857385; 22138524; 22089644; 23207808; 23430490; 23649758; 23688858 AGMX2 323 179 Agammaglobulinemia, X-linked 2 XL Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described with early-onset, severe infections, and awareness may allow preventative measures and early and aggressive treatment of infections may be beneficial 29636373 AGPAT2 325 10555 Lipodystrophy, congenital generalized, type 1 AR Pediatric Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal Cardiovascular; Endocrine; Gastrointestinal Dietary measures (eg, restriction of fat intake to 20-30% of total dietary energy) and medications (eg, leptin, though availability may be limited) may be beneficial; Surveillance for manifestations, including diabetes and cardiac and hepatic manifestations, may allow early diagnosis and treatment 8783769; 11967537; 14602785; 14557463; 15181077; 17671040; 17118991; 19278620; 20301391 AGPS 327 8540 Rhizomelic chondrodysplasia punctata, type 3 AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7807941; 9553082; 21990100 AGRN 329 375790 Myasthenic syndrome, congenital 8 AR Pediatric Musculoskeletal; Neurologic Musculoskeletal; Neurologic; Pharmacogenomic Ephedrine treatment has been reported as effective in affected inviduals; Medical treatment with acetylcholine esterase inhibitors and/or potassium channel blocker 3,4-diaminopyridine may be beneficial in many individuals; In infancy, the use of apnea monitors may be indicated; Agents that affect neuromuscular transmission and exacerbate myasthenic manifestations should be avoided 19631309; 20301347; 22205389; 22678886 AGT 333 183 Renal tubular dysgenesis AR N/A N/A Renal Renal Treatment with fresh frozen plasma in the neonatal period has been reported as effective in terms of maintaing blood pressure and allowing survival 1394429; 8348146; 8513325; 8132767; 7649545; 9120024; 9120002; 9259580; 9421481; 10585456; 11829142; 11731937; 15023884; 16116425; 17047091; 17036344; 20978123; 22685354 AGTPBP1 17258 23287 Childhood-onset neurodegeneration with cerebellar atrophy AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30420557 AGTR1 336 185 Renal tubular dysgenesis AR N/A N/A Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8021009; 16116425; 17668390 AGTR2 338 186 Mental retardation, X-linked 88 XL N/A N/A Neurologic General The evidence of variants as related to disease causation has been questioned due to subsequent population-based studies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12089445; 12746399; 14598163; 14722754; 16463274; 22269148; 23871722 AGXT 341 189 Hyperoxaluria, primary, type 1 AR Pediatric Biochemical; Cardiovascular; Renal Biochemical; Cardiovascular; Renal Fluid intake and medical management (eg, pyridoxine in those who are pyridoxine responsive, potassium/sodium citrate or neutral orthophosphate) can be beneficial to reduce calcium oxalate supersaturation/biosynthesis and reduce stone formation; Organ transplantation (preemptive liver transplantation or liver/kidney transplantation) may be beneficial; Surveillance for renal and related complications (which can include cardiac dysrhythmias) can be beneficial; Dehydration and excessive intake of oxalate-rich foods should be avoided, as well as certain vitamins and medications 449695; 6472428; 3974685; 2887776; 2797068; 2189732; 7969325; 1703535; 2039493; 1961759; 9604813; 10586179; 10453743; 10485304; 11562405; 8507692; 11688375; 12543880; 15327387; 16247357; 15855742; 15464418; 15840016; 15849466; 15767715; 16810517; 16916735; 17460142; 17495019; 18359396; 18282470; 18337715; 19935811; 19571789; 19225556; 19132372; 19479957; 20733487; 20016466; 20301460; 20490484; 22547750; 22821680; 22956877; 23439734; 23810941; 24012869 AGXT2 14412 64902 Beta-aminoisobutyric aciduria AR N/A N/A Biochemical General The clinical significance is unclear 21572414 AHCY 343 191 Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Neurologic Biochemical Dietary restriction (eg, of methionine) and supplementation (eg, of phosphatidylcholine) may be beneficial in some individuals 2380820; 15024124; 20852937; 21732553 AHDC1 25230 27245 Xia-Gibbs syndrome AD N/A N/A Audiologic/Otolaryngologic; Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24791903 AHI1 21575 54806 Joubert syndrome 3 AR N/A N/A Neurologic; Ophthalmologic; Renal General The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial The condition may involve multi-systemic manifestations, including sequelae affecting the renal system, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial 15467982; 15322546; 16155189; 16453322; 20081859; 21937992; 25616960 AHR 348 196 Retinitis pigmentosa 85 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29726989 AHSG 349 197 Alopecia-mental retardation syndrome 1 AR N/A N/A Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28054173 AICDA 13203 57379 Immunodeficiency with hyper-IgM, type 2 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have elevated serum IgM levels and absent IgG, IgA, and IgE, and are thus highly susceptible to severe bacterial infections (eg, bacterial respiratory and GI infections), such that antiinfectious prophylaxis (including with IVIG, which has been reported to be effective) and early and aggressive treatment of infections may be beneficial; Individuals may also have autoimmune and inflammatory manifestions, some of which may benefit from early knowledge and interventions, including hemolytic anemia and immune thrombocytopenia 11007475; 14962793; 15358621; 19575287; 21192628 AIFM1 8768 9131 Deafness, X-linked 5 XL Pediatric Allelic with Combined oxidative phosphorylation deficiency 6 (XL); Charcot-Marie-Tooth disease X-linked recessive 4, with or without cerebellar ataxia (Cowchock syndrome) (XL); Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy (XL) Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Musculoskeletal; Neurologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 16816020; 20362274; 22019070; 23217327; 25986071; 27102849; 28842795 AIMP1 10648 9255 Leukodystrophy, hypomyelinating, 3 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21092922; 21397066; 21397067; 24958424 AIMP2 20609 7965 Leukodystrophy, hypomyelinating, 17 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29215095 AIP 358 9049 Pituitary adenoma 1, multiple types AD Pediatric Endocrine; Oncologic Endocrine; Oncologic Multiple tumor types have been described Surveillance and/or awareness of cancer risk may allow early diagnosis of pituitary tumors (as well as related manifestations, such as hypertension, hypogonadism, diabetes mellitus, and osteoporosis), which could potentially be beneficial to allow early medical (eg, with somatostatin analogs, growth hormone receptor antagonists, dopamine agonists) or surgical treatment; Surveillance post-treatment may also be beneficial to detect recurrence/new adenomas 7621566; 11158006; 16728643; 17299063; 22319033; 17609395; 17244780; 17360484; 17341560; 18381572; 20570174; 20685857; 19945022; 20506337; 20507346; 21591954; 21753072; 22319033; 22720333; 22612670; 23270713; 23321498; 23674160; 23743763; 24078436 AIPL1 359 23746 Leber congenital amaurosis 4; Retinitis pigmentosa, juvenile, AIPL1-related; Cone-rod dystrophy, AIPL1-related AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10711674; 10615133; 10873396; 21602930; 21900377; 21474771; 22412862 AIRE 360 326 Autoimmune polyendocrinopathy syndrome, type I, with or without reversible metaphyseal dysplasia AD/AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Ophthalmologic Allergy/Immunology/Infectious; Endocrine Individuals need life-long follow-up, as sequelae may appear later in life; Endocrine findings can include adrenocortical failure and severe hypocalcemia; Infectious complications, such as candiasis, and septicemia, are frequent, and prompt and aggressive treatment of infections may be beneficial 7024719; 3496374; 2348835; 1453436; 9398840; 9398839; 9543115; 9837820; 9717837; 11018166; 11600535; 14557425; 16965330; 17539912; 19758376; 19807739; 25926518 AK1 361 203 Adenylate kinase deficiency, hemolytic anemia due to AR Pediatric Hematologic; Neurologic Hematologic Individuals present with hemolytic anemia (as well as neurodevelopmental features, at least in some reported individuals), and splenectomy has reported as being effective in treatment of hemolysis 179026; 5546784; 6308059; 2542324; 7947281; 9432020; 17662886 AK2 362 204 Reticular dysgenesis AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic Allergy/Immunology/Infectious; Audiologic/Otolaryngologic Individuals typically die in early infancy due to severe infections; Early diagnosis allowing HSCT can be effective 13840590; 6132037; 19043416; 19043417 AK7 20091 122481 Spermatogenic failure 27 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29365104 AKAP9 379 10142 Long QT syndrome 11 AD Pediatric Cardiovascular Cardiovascular In order to prevent sequelae including syncope, cardiac arrest and sudden death prophylactic use of beta blockers in asymptomatic individuals may be beneficial; ICD may be indicated for individuals refractory to beta-blocker treatment or with history of cardiac arrest; Agents that can contribute to prolonged QT or related dysrhythmias should be avoided, as should activities associated with high stress/intense exertion 10220144; 18093912; 20809527; 21430528; 20301308 AKR1C2 385 1646 46,XY sex reversal 8 AR Pediatric Endocrine; Genitourinary; Oncologic Genitourinary; Oncologic Surveillance and/or awareness of cancer risk, and preventive measures may be beneficial to reduce the risk of gonadal tumors 4352099; 21802064 AKR1D1 388 6718 Bile acid synthesis defect, congenital, 2 AR Pediatric Gastrointestinal Gastrointestinal Early interventions, such as bile replacement therapy, can be beneficial, though liver transplant may be necessary in severe cases 2897546; 3198770; 2072042; 2248502; 8707100; 12970144; 15030995; 20522910; 23160874 AKT1 391 207 Cowden syndrome 6; Proteus syndrome AD Pediatric Cardiovascular; Dermatologic; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Oncologic; Pulmonary Cardiovascular; Hematologic; Oncologic; Pulmonary In Proteus syndrome, variants may be found on peripheral blood testing, but affected tissue must typically be tested for molecular diagnosis In Cowden syndrome, individuals have been described with manifestations including breast, renal, and thyroid cancer, and surveillance may allow early detection and management of neoplasms; In Proteus syndrome, individuals may be at risk for a variety of manifestations, some of which may be occult; Surveillance for hematologic/vascular manifestations (eg, deep vein thrombosis and pulmonary embolism) can allow early detection and treatment; Surveillance for pulmonary disease (as patients are at risk for restrictive lung disease) can allow early detection and treatment; As individuals may be at increased risk for neoplastic processes, routine monitoring by history and physical examination (without separate imaging) may allow early detection of neoplasms 21793738; 22876373; 23246288 AKT2 392 208 Hypoinsulinemic hypoglycemia with hemihypertrophy AD Pediatric Endocrine; Musculoskeletal Endocrine Individuals may present early in life with severe hypoglycemia (and related sequelae, including seizures and death), and in order to prevent severe hypoglycemia, specific feeding regimens (eg, overnight enteral carbohydrate feeding) may be beneficial 15166380; 14764948; 19164855; 21979934 AKT3 393 10000 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 AD N/A N/A Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22729224; 22729223; 23745724 ALAD 395 210 Porphyria, acute hepatic AR Pediatric Biochemical; Gastrointestinal; Neurologic Biochemical; Pharmacogenomic Digenic inheritance (with CPOX) has been described Medical treatment (eg, with agents such as infusion of heme arginate) can be effective; Affected individuals are endangered by certain agents, including alcohol ingestion or lead exposure 513604; 3559484; 2600550; 2063868; 7490911; 9732973; 1905639; 1716854; 1569184; 9516683; 11071662; 10706561; 11342419; 15303011; 16343966; 16398658; 17236137; 17366816 ALAS2 397 212 Anemia, sideroblastic 1; Protoporphyria, erythropoietic, X-linked XL Pediatric Dermatologic; Gastrointestinal; Hematologic Dermatologic; Gastrointestinal; Hematologic In X-linked sideroblastic anemia, phlebotomy can be effective to prevent the development of complications such as cardiovascular and liver damage, as well as diabetes, and is typically most effective in individuals who are pyridoxine-responsive; In Erythropoietic protoporphyria, sunlight protection (and possibly beta-carotene and alpha-melanocyte treatments) may be beneficial, as well as medical treatment of hepatic manifestations (eg, with cholestyramine, plasmapharesis and IV hemin), though liver transplantations may be necessary, while BMT has been reported as effective 14247476; 130377; 1570328; 7949148; 7560104; 10029606; 10886220; 12531813; 16315313; 16735131; 18760763; 19144952; 19656325; 21252495; 23016163; 23263862 ALB 399 213 Hyperthyroxinemia, familial dysalbuminemic; Analbuminemia AD/AR Pediatric Allelic with Bisalbuminemia (AD); Paralbuminemia (AD); Dysalbuminemic hyperzincemia (AD) Endocrine; Musculoskeletal; Renal Endocrine; Pharmacogenomic; Renal Depending on the disorder, manifestations may primarily affect the endocrine system (as in Dysalbuminemic hyperthyroxinemia) or may result in findings such as edema and hypercholesterolemia, as well as pharmacogenomic implications (as in Analbuminemia) In Dysalbuminemic hyperthyroxinemia, genetic diagnosis may help avoid unecessary treatment; In Analbuminemia, medical treatment of sequelae of low albumin (eg, dysplipidemia) can be beneficial, and precautions with certain medications may be indicated 13673098; 13785411; 14187073; 5926635; 1269174; 2430733; 3578276; 3407659; 3353369; 2762316; 2404284; 2104980; 6310605; 7829599; 8048949; 8064810; 8621984; 9329347; 9589637; 10842774; 10946882; 11781148; 12099390; 12743361; 15541334; 15300429; 16183048; 15996651; 18459107; 20638375; 20415703; 22327004; 22227324 ALDH18A1 9722 5832 Cutis laxa, autosomal dominant 3; Spastic paraplegia 9A, autosomal dominant; Cutis laxa, autosomal recessive, type IIIA; Spastic paraplegia 9B, autosomal recessive AD/AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9643297; 11092761; 18478038; 21739576; 24913064; 26026163; 26297558; 26320891 ALDH1A3 409 220 Microphthalmia, isolated 8 AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23312594 ALDH3A2 403 224 Sjogren-Larsson syndrome AR N/A N/A Biochemical; Dermatologic; Neurologic; Ophthalmologic General Medical treatment (eg, with Zileuton) may be beneficial for certain aspects Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13354244; 13457946; 8176565; 9027499; 9829906; 11124298; 11408337; 16476818; 21684788; 21872273; 22397046; 22426667; 22833178; 23034980; 25784589; 31512987 ALDH4A1 406 8659 Hyperprolinemia, type II AR N/A N/A Biochemical; Neurologic General The clinical relevance of the condition is unclear 9700195; 10780262 ALDH5A1 408 7915 Succinic semialdehyde dehydrogenase deficiency AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7226548; 6627675; 9266358; 9093300; 9683595; 12743223; 14635103; 15059623; 17438226; 20304328; 21612881; 22437753; 32887777 ALDH6A1 7179 4329 Methylmalonate semialdehyde dehydrogenase deficiency AR Pediatric Biochemical Biochemical Some individuals have been reported as asymptomatic Dietary management (eg, with low-protein, valine restricted diet) has been reported as beneficial 3939535; 3117077; 9787093; 10947204; 21863277; 32151545 ALDH7A1 877 501 Epilepsy, pyridoxine-dependent AR Pediatric Neurologic Neurologic Individuals frequently present in the neonatal period with seizures (neonatal lactic acidosis and hypoglycemia have also been described), and the seizures, though otherwise refractory to other anti-epileptics, can typically be controlled via medical management (daily pyridoxine monotherapy), though the condition may still impact longer-term developmental manifestations 13133562; 14131641; 3977296; 16159904; 16075246; 16491085; 17068770; 17721876; 21704546; 20301659; 22529283; 22728861; 22804844; 23054014; 28331464 ALDOA 414 226 Glycogen storage disease XII AR Pediatric Biochemical; Hematologic; Musculoskeletal; Neurologic; Renal Biochemical; Hematologic; Renal Individuals can have rhabdomyolysis from stressors such as febrile illness, and appropriate precautions and management may be beneficial; Aldolase A deficiency is also asociated with hereditary hemolytic anemia, and transfusions and splenectomy have been described in treatment 4788792; 7331996; 3688035; 2825199; 8598869; 14615364 ALDOB 417 229 Fructose intolerance, hereditary AR Pediatric Biochemical; Gastrointestinal; Neurologic; Renal Biochemical; Gastrointestinal Clinical manifestations, which can be severe/fatal, occur with the dietary introduction of fructose or sucrose, and dietary measures (fructose restriction) can be effective 13358219; 14060577; 13942402; 13959929; 4166890; 5637008; 4212946; 213970; 491970; 6888454; 3383242; 2916618; 2349937; 1967768 ; 2314976; 2122082; 8535439; 9610797; 18541450; 20848650; 20882353; 22375183 ALG1 18294 56052 Congenital disorder of glycosylation, type Ik AR Pediatric Biochemical; Gastrointestinal; Hematologic; Neurologic; Renal Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 14709599; 14973782; 14973778; 20679665; 22966035 ALG11 32456 440138 Congenital disorder of glycosylation, type Ip AR Pediatric Biochemical; Hematologic; Neurologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 20080937; 22213132; 30676690 ALG12 19358 79087 Congenital disorder of glycosylation, type Ig AR Pediatric Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Hematologic Hepatic-metabolized agents should be avoided As the condition can include immunodeficiency and frequent infections, prophylaxis and early and aggressive treatment of infections may be beneficial; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 11983712; 12217961; 17506107 ALG13 30881 79868 Developmental and epileptic encephalopathy 36 XL N/A N/A Craniofacial; Neurologic General One patient has been reported with a phenotype described as consistent with a congenital disorder of glycosylation, but subsequent patients did not have similar features Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22492991; 23033978; 23934111; 24781210; 26138355 ALG14 28287 199857 Myasthenic syndrome, congenital 15 AR Pediatric Musculoskeletal; Neurologic Musculoskeletal; Neurologic Individuals have been described as manifesting with progressive weakness, and have been reported who have demonstrated long-term benefit from medical treatment (with anticholinesterase medication) 23404334 ALG2 23159 85365 Congenital disorder of glycosylation, type Ii; Myasthenic syndrome, congenital 14 AR Pediatric Craniofacial; Biochemical; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Hematologic; Musculoskeletal; Neurologic Hepatic-metabolized agents should be avoided In Congenital disorder of glycosylation, type Ii, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery; In Myasthenic syndrome, congenital, individuals have been described as manifesting with progressive weakness, and have been reported who have benefited from medical treatment (with anticholinesterase medication) 12684507; 23404334; 24461433; 30397276 ALG3 23056 10195 Congenital disorder of glycosylation, type Id AR Pediatric Biochemical; Hematologic; Neurologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 8552211; 10581255; 15108280; 15840742; 17551933; 18679822 ALG6 23157 29929 Congenital disorder of glycosylation, type Ic AR Pediatric Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 10359825; 10914684; 10924277; 16007612; 21334936 ALG8 23161 79053 Congenital disorder of glycosylation, type Ih AR Pediatric Allelic with Polycystic liver disease 3 with or without kidney cysts (AD) Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Neurologic; Renal Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 12480927; 15235028; 19648040; 19688606; 22306853; 28375157 ALG9 15672 79796 Congenital disorder of glycosylation, type Il AR Pediatric Allelic with Gillessen-Kaesbach-Nishimura syndrome (AR) Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Pulmonary; Renal Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 15148656; 15945070; 19451548; 25966638 ALK 427 238 Neuroblastoma, susceptibility to, 3 AD Pediatric Oncologic Oncologic Surveillance (eg, with frequent abdominal ultrasound and urinary catecholamine testing) and awareness of cancer risk may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality 18923523; 18724359; 18242317; 20301782 ALKBH8 25189 91801 Intellectual developmental disorder, autosomal recessive 71 AR N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31079898 ALMS1 428 7840 Alstrom syndrome AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Ophthalmologic; Renal Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Ophthalmologic; Renal The condition may be recognizable from early manifestations (eg, related to visual loss), but dilated or restricted cardiomyopathy is common, and measures to decrease related morbidity and mortality may be beneficial; Management related to other sequelae, such as endocrine (eg, diabetes mellitus), renal, and hepatic manifestations, may also be beneficial; Recognition of hearing impairment can allow interventions related to speech and language development 13649370; 5824738; 3766665; 3687707; 2231654; 1746604; 8418611; 8488920; 8636816; 9066877; 9409865; 9663233; 11343329; 11941369; 11941370; 17594715; 17850632; 22043170; 21522186; 20301444; 25864795 ALOX12B 430 242 Ichthyosis, congenital, autosomal recessive 2 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11773004; 16116617; 20301593 ALOX5 435 240 Asthma, diminished response to antileukotriene treatment in AD Pediatric General Pharmacogenomic Variants may have pharmacogenomic importance 9062372; 9698605; 10369259; 14702425 ALOXE3 13743 59344 Ichthyosiform erythroderma, congenital, nonbullous, 1 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11773004; 16116617; 19131948; 20301593 ALPK1 20917 80216 Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome AD Pediatric Gastrointestinal; Hematologic; Neurologic; Ophthalmologic Gastrointestinal The condition can include splenomegaly and related sequelae, such as cytopenia, and splenectomy has been described as being indicated in some individuals 22307799; 30967659; 31939038 ALPK3 17574 57538 Cardiomyopathy, familial hypertrophic 27 AD/AR Pediatric Cardiovascular Cardiovascular Individuals may manifest with early-onset, severe cardiomyopathy, and awareness may allow medical and/or surgical management; Heterozygotes may also be at increased risk of cardiomyopathy, and awareness may be beneficial to allow surveillance and potential management 26846950; 27106955; 28223422 ALPL 438 249 Hypophosphatasia, infantile; Hypophosphatasia, childhood; Hypophosphatasia, adult; Odontohypophosphatasia AD/AR Pediatric Dental; Endocrine; Musculoskeletal; Neurologic Endocrine; Neurologic In some forms, abnormal calcium levels can be treated; Seizures can be treated with vitamin B6; Bisphosphonates and excess vitamin D should be avoided due to potential hypercalcemia leading to renal damage; Enzymatic therapy has shown benefit in individuals with severe forms of hypophosphatasia 18110134 ; 13800162; 4288761; 4309618 ; 5013867; 7235780; 7305584; 7072744; 7182980; 3960066; 1409720; 3174660; 8406453; 10332035; 10872988; 11479741; 11999978; 12357339; 17519318; 17213282; 21488855; 20978533; 20301329; 22397652 ALS2 443 57679 Spastic paralysis, infantile onset ascending; Primary lateral sclerosis, juvenile; Amyotrophic lateral sclerosis 2 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2328408; 7920663; 8745388; 11586298; 11586297; 12145748; 12509863; 16718699; 18523452; 18810511; 19122027 ALS2CL 20605 259173 Schizophrenia AD N/A N/A Neurologic General Evidence or clinical applicability is unclear 21743468; 23425335 ALX1 1494 8092 Frontonasal dysplasia 3 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20451171 ALX3 449 257 Frontonasal dysplasia 1 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17963218; 19409524; 22106187 ALX4 450 60529 Parietal foramina 2; Frontonasal dysplasia 2 AD/AR N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Variants may contribute to nonsyndromic craniosynostosis Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11106354; 11137991; 16319823; 18541970; 19692347; 20301307; 22140057; 22829454; 23401352; 24668755; 24764194 AMACR 451 23600 Bile acid synthesis defect, congenital, 4; Alpha-methylacyl-CoA racemase deficiency AR Pediatric Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic Biochemical; Gastrointestinal; Hematologic Individuals with Bile acid synthesis defect, congenital, 4 may present with manifestations of hepatic disease, and medical therapy (eg, with oral cholic acid, and Vitamin K for bleeding) has been reported as beneficial; In Alpha-methylacyl-CoA Racemase deficiency, early diagnosis may allow potentially benefical dietary/medical therapy (eg, restriction of dietary phytanic acid and pristanic acid) 9584266; 10655068; 11473573; 12512044; 15249642; 18032455; 20821052; 21576695; 23286897 AMBN 452 258 Amelogenesis imperfecta type IF AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24858907 AMCN 456 261 Arthrogryposis multiplex congenita, neurogenic AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5491443; 28317099 AMELX 461 265 Amelogenesis imperfecta, type 1E XL N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1916828; 7782077; 15111628 AMER1 26837 139285 Osteopathia striata with cranial sclerosis XL N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19079258; 20209645; 20950377; 22987541 AMH 464 268 Persistent Mullerian duct syndrome, type I AR Pediatric Endocrine; Genitourinary; Oncologic Endocrine; Oncologic; Genitourinary In males, recognition can allow surveillance and surgical explorations to correct manifestations such as cryptorchdisim, which can be important to preserve fertility and decrease the chance of related sequelae (eg, testicular tumors) 8872466; 8895659; 11760020; 15878900; 18547961; 22188863 AMHR2 465 269 Persistent Mullerian duct syndrome, type II AR Pediatric Endocrine; Genitourinary; Oncologic Endocrine; Oncologic; Genitourinary In males, recognition can allow surveillance and surgical explorations to correct manifestations such as cryptorchdisim, which can be important to preserve fertility and decrease the chance of related sequelae (eg, testicular tumors) 8162013; 7493017; 8872466; 8895659; 15878900; 19457927 AMMECR1 467 9949 Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis XL Pediatric Audiologic/Otolaryngologic; Craniofacial; Hematologic; Musculoskeletal; Renal Hematologic Ellipsocytosis requiring red blood cell transfusion has been described, and awareness may allow early diagnosis and management 27811305; 28089922 AMN 14604 81693 Imerslund-Grasbeck syndrome 2 AR Pediatric Gastrointestinal; Hematologic; Renal Gastrointestinal Early diagnosis is beneficial, as early detection may allow life-long medical treatment with parenteral hydroxocobalamin, which can ameliorate morbidity and mortality 12590260; 17114957; 17285242; 18181028; 22078000; 22854512; 22631584 AMPD1 468 270 Myoadenylate deaminase deficiency AR N/A N/A Biochemical; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1631143; 10086964; 10996775; 11102975; 11331279; 22538307 AMPD2 469 271 Pontocerebellar hypoplasia type 9; Spastic paraplegia 63 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23911318; 24482476; 27066553 AMPD3 470 272 Erythrocytic AMP deaminase deficiency AD/AR N/A N/A General General The condition may not be clinically relevant 3804327; 7881427; 8004104 AMT 473 275 There is no current effective treatment for severe disease; however, children with variants associated with residual GCS enzyme activity treated aggressively early with sodium benzoate and N-methyl D-aspartate receptor site antagonists may have improved outcomes; Valproate should be avoided AR Pediatric Biochemical; Neurologic; Ophthalmologic Biochemical; Pharmacogenomic There is no current effective treatment for severe disease; however, children with mutations associated with residual GCS enzyme activity treated aggressively early with sodium benzoate and N-methyl D-aspartate receptor site antagonists may have improved outcomes; Valproate should be avoided 11139253; 12948742; 16151895; 16450403; 20301531; 19299230; 21470805; 28462797 AMTN 33188 401138 Amelogenesis imperfecta, type IIIB AD N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27412008 ANAPC1 19988 64682 Rothmund-Thomson syndrome, type 1 AR Pediatric Craniofacial; Dental; Endocrine; Dermatologic; Genitourinary; Musculoskeletal; Ophthalmologic Endocrine Awareness of endocrine manifestations, including growth hormone deficiency, may allow early recognition and treatment 31303264 ANG 483 283 Amyotrophic lateral sclerosis 9 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15557516; 16501576; 17886298; 18087731; 18852347; 19153377; 20577002 ANGPT2 485 285 Lymphatic malformation 10 AD Pediatric Allergy/Immunology/Infectious; Cardiovascular Allergy/Immunology/Infectious The condition involves lymphatic malformations, and in some individuals, progression to cellulitis has been reported, such that awareness may allow prompt treatment of infectious sequelae 32908006 ANGPTL3 491 27329 Hypobetalipoproteinemia, familial, 2 AR N/A N/A Gastrointestinal General Unlike hypobetalipoproteinemia due to variants in APOB, individuals with variants in ANGPTL3 do not appear to to have increased susceptibility to hepatic steatosis or gastrointestinal or cardiovascular manifestations compared to unaffected relatives; Heterozygous individuals may demonstrate laboratory-based manifestations (eg, lower plasma LDL and triglycerides) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9508071; 9508071; 20942659; 22659251 ANK1 492 286 Spherocytosis, type 1 AD/AR Pediatric Hematologic Hematologic Some individuals may have therapy requiring neonatal hyperbilirubinemia, as well as severe, transfusion-requiring anemia 14467968; 4476391; 2675425; 1832935; 1486040; 8640229; 9887280; 9430667; 17327413; 20512576; 32436265 ANK2 493 287 Long QT syndrome, 4; Cardiac arrhythmia, ankyrin-B-related AD Pediatric Cardiovascular Cardiovascular Individuals may present with a variety of manifestations depending on the type of arrhythmia, including stress/exercise-induced arrhythmias, syncope, and sudden cardiac death, and surveillance (eg, with electrocardiogram) and medical (eg, including ICD placement) management may be effective to prevent severe sequelae of cardiac arrhythmias 7485162; 12571597; 15178757; 17242276; 17940615; 18790697; 18832177; 20809527; 21859974 ANK3 494 288 Mental retardation, autosomal recessive, 37 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23390136; 29302074 ANKH 15492 56172 Craniometaphyseal dysplasia, autosomal dominant; Chondrocalcinosis 2 AD N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8528213; 9915952; 11326272; 11326338; 12297987; 12297989; 20301634; 20358596; 22150416; 22647861 ANKLE2 29101 23141 Microcephaly, primary autosomal recessive, 16 AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25259927 ANKRD11 21316 29123 KBG syndrome AD N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15523620; 15378538; 21782149; 22307766; 25125236 ANKRD26 29186 22852 Thrombocytopenia 2 AD Pediatric Hematologic Hematologic A variant in ABCD5 was reported as causative Individuals may have bleeding tendency, and awareness may allow precautions (eg, in surgical situations) and prompt treatment, which may be beneficial 10541317; 10521306; 10891439; 20626622; 21211618 ANKS6 26724 203286 Nephronophthisis 16 AR N/A N/A Cardiovascular; Gastrointestinal; Renal General Renal transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23793029 ANLN 14082 54443 Focal segmental glomerulosclerosis 8 AD Pediatric Renal Renal Renal transplant has been described The condition can involve renal failure, and early diagnosis may enable management considerations; Renal transplant has been described 24676636 ANO10 25519 55129 Spinocerebellar ataxia, autosomal recessive 10 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21092923; 22008874 ANO3 14004 63982 Dystonia 24 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23200863 ANO5 27337 203859 Gnathodiaphyseal dysplasia AD Pediatric Allelic with Miyoshi muscular dystrophy 3 (AR); Muscular dystrophy, limb-girdle, autosomal recessive 12 (AR) Allergy/Immunology/Infectious; Musculoskeletal Allergy/Immunology/Infectious Individuals have been reported as being frequently affected by osteomyelitis of the jaw, and awareness of the risk may allow early detection and management of lesions 5816667; 9673985; 15124103; 17132147; 17008331; 20096397; 20692837; 21186264; 22951575; 21820307; 22402862; 22499103; 23047743 ANO6 25240 196527 Scott syndrome AR Pediatric Hematologic Hematologic Though manifestations tend to be milder than in other bleeding disorders, precautions related to certain circumstances, such as in surgery, may be beneficial 572637; 7989579; 21107324 ANOS1 6211 3730 Kallmann syndrome 1 XL/Digenic Pediatric Audiologic/Otolaryngologic; Craniofacial; Dental; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Renal Audiologic/Otolaryngologic; Endocrine Digenic inheritance (with PROKR2) has been reported Surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required; As the condition may include hearing loss, recognition and interventions related to speech and language development may be beneficial 6772660; 3312278; 3101500; 8504298; 7677154; 8989261; 9713559; 10944855; 11297579; 15001591; 8768867; 16882753; 8160472; 20301509; 20949504; 23533228 ANTXR1 21014 84168 Hemangioma, capillary infantile, susceptibility to; Growth retardation, alopecia, pseudoanodontia, and optic atrophy (GAPO syndrome) AD/AR N/A N/A Craniofacial; Dental; Dermatologic; Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9180938; 9298746; 18931684; 19367160; 23602711 ANTXR2 21732 118429 Hyaline fibromatosis syndrome AR Pediatric Allergy/Immunology/Infectious; Dental; Dermatologic; Gastrointestinal; Musculoskeletal Allergy/Immunology/Infectious; Dermatologic; Musculoskeletal The condition may be clinically recognizable, but involves manifestations that require clinical care, such as fracture susceptibility, intractable diarrhea, and infection susceptibility, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 20896407; 20896998; 55105; 2434938; 2433666; 3544844; 487969; 11206353; 12214284; 11298373; 12973667; 14508707 ANXA11 535 311 Amytrophic lateral sclerosis 23 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28469040 AP1B1 554 162 Keratitis-ichthyosis-deafness syndrome, autosomal recessive AR N/A N/A Audiologic/Otolaryngologic; Dermatologic Audiologic/Otolaryngologic The condition may include hearing loss, recognition and interventions related to speech and language development may be beneficial 31630788; 31630791 AP1S1 559 1174 MEDNIK syndrome AR Pediatric Audiologic/Otolaryngologic; Biochemical; Dermatologic; Neurologic Audiologic/Otolaryngologic; Biochemical As the condition may include hearing loss, recognition and interventions related to speech and language development may be beneficial; The condition involves abnormal copper metabolism, and medical management (with Zinc acetate) has been shown to be beneficial related to both lab-based as well as clinical outcomes 19057675; 23423674; 23622398; 24754424 AP1S2 560 8905 Mental retardation, X-linked syndromic, Fried type (Pettigrew syndrome) XL N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5054319; 10398241; 12599187; 17617514; 18428203; 19377476; 2018058; 22210230; 23756445 AP1S3 18971 130340 Psoriasis 15, pustular, susceptibility to AD N/A N/A Allergy/Immunology/Infectious; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24791904 AP2M1 564 1173 Intellectual developmental disorder, autosomal dominant 60, with seizures AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31104773 AP2S1 565 1175 Hypocalciuric hypercalcemia, familial, type III AD Pediatric Endocrine Endocrine The condition can involve parathyroidectomy-refractory sequelae of hypercalcemia such as headaches, fatigue, and pain, and medical treatment (eg, with cinacalcet) has been reported as benefical related to symptoms as well as biochemical parameters 23222959; 27050234 AP3B1 566 8546 Hermansky-Pudlak syndrome 2 AR Pediatric Allergy/Immunology/Infectious; Dental; Dermatologic; Hematologic; Neurologic; Ophthalmologic; Pulmonary Allergy/Immunology/Infectious; Dermatologic; Hematologic; Pulmonary Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination 10024875; 11809908; 16507770; 16537806; 20301464; 23215637 AP3B2 567 8120 Developmental and epileptic encephalopathy 48 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27431290; 27431290 AP3D1 568 8943 Hermansky-Pudlak syndrome 10 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Neurologic; Ophthalmologic Allergy/Immunology/Infectious The condition can involve neutropenia and susceptibility to infections, and prompt and aggressive treatment of infections may be beneficial 26744459 AP4B1 572 10717 Spastic paraplegia 47, autosomal recessive AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21620353; 22290197; 24700674; 24781758 AP4E1 573 23431 Stuttering, familial persistent, 1; Spastic paraplegia 51, autosomal recessive AD/AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21620353; 20972249; 21937992; 24700674; 26544806 AP4M1 574 9179 Spastic paraplegia 50, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19559397; 21937992 AP4S1 575 11154 Spastic paraplegia 52, autosomal recessive AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21620353 AP5Z1 22197 9907 Spastic paraplegia 48, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20613862; 22554690 APC 583 324 Familial adenomatous polyposis 1; Desmoid disease, hereditary; Gastric adenocarcinoma and proximal polyposis of the stomach AD Pediatric Dental; Dermatologic; Musculoskeletal; Oncologic; Ophthalmologic Oncologic Gastric adenocarcinoma and proximal polyposis of the stomach results from variants in the APC gene promoter 1B Depending on the specific APC-related condition, individuals may be at risk for a variety of neoplasms, and surveillance (including for gastric adenocarcinoma, thyroid disease, duodenal and colonic neoplasms, and hepatoblastoma, the latter with ultrasound and serum AFP measurement, as well as for other types of neoplastic manifestations) may allow early detection and management, which may reduce morbidity and mortality; In FAP, medical management (with NSAIDs) have been reported to result in adenoma regression and decreased polyp number; Colectomy is indicated when a specific numeric/pathologic adenomatous burden has been reached; Prophylactic gastrectomy has been described in Gastric adenocarcinoma and proximal polyposis of the stomach 14902760; 14933371; 13707264; 13891268; 13946545; 14136536; 5644968; 5660317; 5660235; 5443116; 4739325; 4853059; 1111674; 856075; 880737; 739523; 758668; 7446647; 7296952; 7067564; 6121129; 7172944; 6887943; 6129922; 6690356; 2435780; 2827474; 3033343; 3821797; 3800608; 2848134; 2848134; 3338026; 2896968; 3354603; 2156161; 1658283; 1651174; 1651563; 1324223; 1317264; 1329510; 1314729; 1544113; 1316610; 1316858; 8281160; 8276387; 8244107; 8105087; 8385741; 8037405; 8064829; 7661930; 8826936; 8940264; 8940262; 8968744; 9215849; 9585611; 10504375; 10077730; 10782927; 10815155; 10874062; 11932472; 12621137; 17135589; 18395100; 19793053; 20301519; 20400027; 20105204; 21813476; 22305464; 22773231; 22886683; 27087319; 27343414; 31409086; 33242120 APC2 24036 10297 Sotos syndrome 3; Cortical dysplasia, complex, with other brain malformations 10 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25753423; 31585108 APCDD1 15718 147495 Hypotrichosis 1 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10878665; 20393562; 22512811 APOA1 600 335 Hypoalphalipoproteinemia, primary 2; Amyloidosis, familial visceral AD/AR Pediatric Cardiovascular; Endocrine; Dermatologic; Gastrointestinal; Ophthalmologic; Renal Cardiovascular; Endocrine; Gastrointestinal; Pharmacogenomic Though manifestations have been described in adults, surveillance and interventions should likely begin in the pediatric period In Hypoalphaliproteinemia, intervention to decrease risk factors contributing to cardiovascular disease (eg, CAD and stroke), as well as early surveillance and intervention in the case of findings such as CAD, may be beneficial; In Amyloidosis, individuals may manifest with sequelae affecting multiple organ systems, and awareness may allow early diagnossi and medical management (eg, related to endocrine or renal insufficiency); Liver transplantation can correct the underlying metabolic defect 4304452; 7430351; 6776144; 7249374; 7080131; 7078608; 6818131; 6308458; 6131168; 6401735; 6401735; 3118360; 3141894; 2512329; 2512329; 1901417; 1502149; 8240372; 8282791; 7981179; 8675681; 9514407; 9916936; 10487826; 9931341; 12270762; 12050338; 17991432; 21122686; 21443680; 21875686; 29446975; 30665372 APOA2 601 336 Apolipoprotein A-II deficiency AR N/A N/A Cardiovascular General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2107739; 12522687; 24387992 APOA5 17288 116519 Hyperlipoproteinemia, type V AD/AR Pediatric Cardiovascular; Gastrointestinal Cardiovascular Variants in additional genes may contribute to phenotypic manifestations Individuals may have severe hypertriglyceridemia, and interventions related to factors that contribute to cardiovascular sequelae (including through diet and exercise control) may be beneficial, though individuals may develop refractory hypertriglyceridemia 16143024; 16200213; 19410254; 19447388; 21993410; 22239554 APOB 603 338 Hypercholesterolemia, familial, 2; Hypobetalipoproteinemia, familial 1 AD/AR Pediatric Cardiovascular; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic Cardiovascular; Gastrointestinal Variants in multiple related genes (eg, LDLR) may have additive effects Some variants may be associated with familial hypercholesterolemia, and dietary/lifestyle/medical measures (eg, with statins) may be beneficial to reduce the risk of sequelae including coronary artery disease, with evidence that early diagnosis and management improves outcomes; In hypobetalipoproteinemia, dietary measures (eg, with a low fat diet and supplementation of essential fatty acids and fat-soluble vitamins) can be beneficial, and early initiation can prevent/decrease severe sequelae; In Hypercholesterolemia, familial, 2, medical management (with inclisiran, a small interfering RNA), has shown evidence of benefit related to parameters such as LDL levels 221546; 7229035; 3771801; 3680528; 3473077; 3584472; 2843815; 2903181; 3399894; 2567736; 2574033; 2563166; 3477815; 2614276; 2725600; 2280177; 2164382; 2310429; 2312735; 1939657; 2022744; 1360085; 1562615; 1600334; 1424233; 1466657; 8215738; 8318993; 8318509; 7711417; 8305410; 8004802; 7883971; 8723684; 8792774; 9108789; 9081691; 9603795; 10952765; 11781700; 11494965; 11940084; 12124991;15984016; 17158591; 18492086; 18354102; 20686565; 21981844; 24288038; 31618540; 32187462; 32197277 APOC2 609 344 Apolipoprotein C-II deficiency (Hyperlipoproteinemia, type Ib) AR Pediatric Cardiovascular; Gastrointestinal; Neurologic Cardiovascular; Gastrointestinal Depending on the severity of disease, individuals may present with manifestations ranging from neonatal encephalopathy to episodic acute pancreatitis, and dietary measures (eg, with low-fat diet, and medium-chain triglyceride supplementation in infancy) can be beneficial to help control lipid abnormalities, including decreasing the risk of episodes of acute pancreatitis; Treatment of acute pancreatitis involves fasting with low-calorie infusion, but serum triglycerides can also be rapidly decreased in emergent situations through normal plasma transfusion; Medical treatment (eg, with fibrates) may be beneficial in adults 565877; 213719; 227429; 6101731; 6475985; 3944267; 3467353; 3171393; 3225819; 1479292; 2477392; 2501098; 7815420; 10225669; 12049186; 12783430; 16153625; 22129523 APOC3 610 345 Apolipoprotein C-III deficiency AD N/A N/A Cardiovascular General The clinical applicability of Hyperalophalipoproteinemia 2 is unclear, though variants may be related to lower triglyceride levels and protection against cardiovascular disease 2914370; 2022742; 16813599; 19074352; 24941081; 24941082; 25225788 APOE 613 348 Hyperlipoproteinemia, type III; Lipoprotein glomerulopathy; Sea-blue histiocyte disease AD/AR Pediatric Cardiovascular; Gastrointestinal; Hematologic; Neurologic; Renal Cardiovascular; Gastrointestinal; Renal In Hyperlipoproteinemia, type III, dietary and medical measures related to treating abnormal lipid profiles (including apharesis in some individuals) can be beneficial, including as relates to the risk of cardiovascular disease; In LPG, early diagnosis may be advantageous in order to allow medical treatment (eg, with fibrate therapy); In Sea-blue histiocyte disease, individuals may present with splenomegaly with sea-blue histiocytes, hypertriglyceridemia, and thrombocytopenia, and preventive measures and surveillance related to cardiac manifestations may be beneficial, and knowledge that splenectomy can exacerbate hypertriglyceridemia may additionally be advantageous 4242937; 4195998; 6795720; 6289314; 6860421; 6323533; 3721502; 3771793; 3029073; 3038959; 3243553; 2539388; 2556398; 2313204; 2341812; 1864973; 1674745; 1713245; 1360898; 1361196; 1356443; 8488843; 7635945; 7586659; 9176854; 11095479; 15630634; 16094309; 16143024; 16431249; 16690468; 18077821; 20534298; 21534236; 22069485; 22481068; 22949395; 28966924; 30421781; 30685233 APP 620 351 Alzheimer disease, familial; Cerebral amyloid angiopathy AD N/A N/A Cardiovascular; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2111584; 1679289; 1944558; 1671712; 1925564; 1678058; 1303275; 1303239; 1415269; 1520398; 1302033; 1642228; 8290042; 8154870; 9328472; 9754958; 10097173; 10441572; 11063718; 10821838; 11409420; 11528419; 12034808; 15365148; 15668448; 16033913; 16505331; 16369530; 16685645; 17325276; 18413473; 19047566; 19286555; 19225789; 22491860; 22702962; 22801501; 22815225; 23102935 APPL1 24035 26060 Maturity-onset diabetes of the young, type 14 AD N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26073777 APRT 626 353 Adenine phosphoribosyltransferase deficiency AR Pediatric Biochemical; Musculoskeletal; Renal Biochemical; Renal Medical and dietary interventions (eg, purine-restricted diet with adequate hydration and allopurinol or febuxostat, in instances where allopurinol can not be used) may be beneficial in order to decrease the severity of manifestations including nephrolithiasis and renal sequelae, as well as to treat individuals with relatively advanced disease; Renal transplant has been described, and disease-specific considerations (eg, immediate postoperative pharmacotherapy) may impact transplant outcomes 5676523; 5763607; 4852180; 1061547; 7766; 865583; 420519; 7311997; 6701033; 3876264; 3680503; 1353080; 806829; 3077470; 3409638; 3343350; 1986109; 1985452; 1353080; 1349689; 1349687; 7915931; 8825602; 9298830; 9521589; 11532677; 14767036; 15025810; 15077874; 15571218; 17126311; 19435978; 20101413; 20150536; 20303634; 20553441; 21635362; 22212387; 22934314; 22988602; 23430916 APTX 15984 54840 Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia AR N/A N/A Gastrointestinal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3239952; 11586299; 11586300; 11294920; 12196655; 14506070; 12629250; 15365154; 15596775;15852392; 15699391; 17572444; 17242337; 18403580; 21465257; 21486904 AQP1 633 358 Blood group, Colton BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 7521540; 7521882; 11606828; 11463012; 11773634 AQP2 634 359 Diabetes insipidus, nephrogenic, autosomal AD/AR Pediatric Endocrine; Renal Endocrine; Renal Individuals can present in infancy with hypernatremia and severe dehydration, and recognition may allow preventive measures and prompt treatment 1828422; 8140421; 7524315; 9649557; 16845277 AQP3 636 360 Blood group, GIL BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 12239222 AR 644 367 Androgen insensitivity; Androgen insensitivity, partial XL Pediatric Allelic with Spinal and bulbar muscular atrophy, X-linked 1 (XL) (a trinucleotide repeat disorder); Hypospadias 1, X-linked (XL) Endocrine; Genitourinary; Neurologic; Oncologic Endocrine; Oncologic; Genitourinary Treatment with testosterone, starting at an early age may enable fertility; Surveillance for breast cancer may be beneficial 17564966; 21057504; 20929961; 22499348 ARCN1 649 372 Rhizomelic short stature with microcephaly, micrognathia, and developmental delay AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27476655 ARF1 652 375 Periventricular nodular heterotopia 8 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28868155 ARFGEF2 15853 10564 Heterotopia, periventricular, autosomal recessive AR N/A N/A Neurologic General In addition to neurologic manifestations, cardiomyoptathy and frequent infections have been described, but this finding may be coincidental; Recurrent infections have been described in several individuals, but it is unclear if this is a primary manifestation or secondary to neurodegenerative sequelae Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12682315; 14647276; 23755938 ARG1 663 383 Hyperargininemia AR Pediatric Biochemical; Neurologic Biochemical; Pharmacogenomic Dietary and medical therapy (eg, with low-protein, arginine restricted diet, sodium benzoate), may be beneficial; Individuals with more severe and earlier presentations (similar to that of other urea cycle disorders) have been reported, and may benefit from similar care to prevent and acute sequelae; Individuals with urea cycle disorders may demonstrate sensitivity to certain agents, such as valproate 1124944; 839368; 624188; 6422160; 3104676; 2913054; 2311630; 2365823; 2246859; 2291040; 8474825; 7649538; 9762606; 12640389; 16963300; 19052914; 19381865; 21229317; 21802329; 21310339; 22959135; 22928720; 22633632; 25135652; 29726057 ARHGAP31 29216 57514 Adams-Oliver syndrome 1 AD N/A N/A Craniofacial; Dermatologic; Musculoskeletal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 474617; 16451141; 19610107; 21565291 ARHGDIA 678 396 Nephrotic syndrome, type 8 AR N/A N/A Renal General Renal transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23434736; 23867502 ARHGEF1 681 9138 Immunodeficiency 62 AR Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic The condition can involve early-onset, recurrent, and severe infections and diagnosis may allow preventative measures and early and prompt treatment of infections (for example, with IVIG); Cancer has been described, and awareness of an increased risk may allow early diagnosis and management 30521495 ARHGEF10 14103 9639 Slowed nerve conduction velocity, autosomal dominant (Hereditary motor and sensory neuropathy) AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9678704; 14508709 ARHGEF18 17090 23370 Retinitis pigmentosa 78 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28132693 ARHGEF2 682 9181 Neurodevelopmental disorder with midbrain and hindbrain malformations AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28453519 ARHGEF6 685 9459 Mental retardation, X-linked 46 XL N/A N/A Neurologic General The evidence of variants as related to disease causation has been questioned due to subsequent population-based studies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9783701; 11017088; 23871722 ARHGEF9 14561 23229 Epileptic encephalopathy, early infantile, 8 XL N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15215304; 21633362; 22612257 ARID1A 11110 8289 Coffin-Siris syndrome 2 (Mental retardation, autosomal dominant 14) AD N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22426308; 22426309 ARID1B 18040 57492 Coffin-Siris syndrome 1 AD N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22405089; 22426308; 22426309 ARID2 18037 196528 Coffin-Siris syndrome 6 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26238514; 28124119; 28884947 ARL13B 25419 200894 Joubert syndrome 8 AR N/A N/A Neurologic; Ophthalmologic; Renal General The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18674751; 20615230; 22241855; 25138100 ARL2 693 402 Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 1 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30945270 ARL2BP 17146 23568 Retinitis pigmentosa with or without situs inversus AR N/A N/A Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Ophthalmologic General Although described patients did not suffer from sequelae as severe as have been reported in other types of ciliary dyskinesia, similar medical interventions may in theory be warranted Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23849777 ARL3 694 403 Joubert syndrome 35; Retinitis pigmentosa 83 AR N/A N/A Craniofacial; Neurologic; Ophthalmologic; Renal General The condition may involve multi-systemic manifestations, including sequelae affecting the renal systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26964041; 30269812 ARL6 13210 84100 Retinitis pigmentosa 55; Bardet Biedl syndrome 3 AR N/A N/A Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal General BBS3 may involve multiple congenital anomalies; Variants may modify severity of BBS due to variants in other BBS-associated genes Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7987310; 9714014; 15258860; 15314642; 19956407; 19858128; 20301537; 23219996 ARL6IP1 697 23204 Spastic paraplegia 61 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24482476 ARMC2 23045 84071 Spermatogenic failure 38 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30686508 ARMC5 25781 79798 ACTH-independent macronodular adrenal hyperplasia 2 AD Adult Endocrine; Oncologic Endocrine; Oncologic Germline variants in this tumor suppressor gene may result in the clinical phenotype in the presence of a second, somatic variant Surveillance for neoplasms, can allow early detection and treatment, which can involve surgical excision of the neoplasm or medical management (eg, targeting aberrant receptor expression) to control cortisol production 19018784; 24283224; 24601692; 24708098; 24905064 ARMC9 20730 80210 Joubert syndrome 30 AR Pediatric Endocrine; Musculoskeletal; Neurologic; Ophthalmologic Endocrine The condition has been described as involving panhypopituitarism, and awareness may allow early diagnosis and medical management (eg, with hormone replacement therapy) 28625504 ARNT2 16876 9915 Webb-Datani syndrome AR Pediatric Craniofacial; Endocrine; Neurologic; Ophthalmologic; Renal Endocrine; Renal The condition may involve multiple pituitary hormone deficiencies, and awareness may allow early recognition and treatment; Awareness of the risk of renal manifestations such as hydronephrosis and vesicoureteral reflux may allow surveillance and renal-protective measures 24022475 ARPC1B 704 10095 Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia AR Pediatric Allergy/Immunology/Infectious; Hematologic Allergy/Immunology/Infectious The condition can involve immunologic abnormalities, including immunodeficiency and vasculitis, and diagnosis may allow preventative measures and early and prompt treatment of infections (for example, with IVIG, immunosuppression, and prophylactic antibiotics); HSCT has been described 27965109; 28368018; 29127144; 30254128; 32499645 ARR3 710 407 Myopia 26, X-linked, female-limited XL N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27829781 ARSA 713 410 Metachromatic leukodystrophy AR N/A N/A Biochemical; Neurologic General The condition can involve multiple congenital anomalies; BMT and CBT, as well as gene therapy, have been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21611375; 5828490; 14206875; 5642751; 5751920; 5367045; 4192207; 2863494; 2876627; 3813937; 1676699; 1678251; 1684088; 1673113; 1673291; 1670590; 15710861; 16966551; 18786133; 19067349; 23845948 ARSB 714 411 Mucopolysaccharidosis type VI (Maroteaux-Lamy) AR Pediatric Biochemical; Cardiovascular; Musculoskeletal; Ophthalmologic Biochemical; Cardiovascular Enzyme replacement therapy is available; The condition can include cardiovascular manifestations, and awareness may allow surveillance and early detection, which may lead to improved management; BMT has been reported 14091597; 6767429; 6776877; 6225949; 6150438; 1832719; 1718978; 1550123; 1301949; 1728449; 8651289; 10070618; 10036316; 11668612; 15324318; 15823680; 15690405; 17643332; 17671068; 21637564; 21930407; 21744090; 22127392; 22669363; 22278137; 22704873; 22864057; 21917494; 22938833; 22133300; 22336888; 22971959; 22495825; 22976768; 23023219; 22405600; 22395531; 25864794; 28595941 ARSG 24102 22901 Usher syndrome, type IV AR N/A N/A Audiologic/Otolaryngologic; Ophthalmologic General The onset of hearing loss has been described as postlingual Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29300381; 32455177; 33300174; 33629623 ARSL 719 415 Chondrodysplasia punctata 1, X-linked recessive XL N/A N/A Craniofacial; Musculoskeletal; Neurologic Musculoskeletal Individuals may demonstrate cervical spine stenosis and/or instability, and surveillance may be beneficial to detect and treat (eg, with placement of a cervical collar or spinal fusion) spinal sequelae 7720070; 9863597; 12567415; 18348268; 20301713; 20523025; 23462608; 23470839 ART4 726 420 Blood group, Dombrock BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 8036791; 9838931; 11001920; 11724986; 12130524; 12028057 ARV1 29561 64801 Developmental and epileptic encephalopathy 38 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25558065; 27270415 ARX 18060 170302 Partington syndrome; Developmental and epileptic encephalopathy 1; Lissencephaly, X-linked 2; Proud syndrome XL N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Conditions can involve multiple congenital anomalies; monitoring for ophthalmologic complications during systemic steroid therapy has been advised; As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3177452; 1605226; 8826464; 9001795; 8826462; 9307258; 10334471; 10398246; 10398242; 10398243; 10353782; 11971879; 11891829; 12485186; 12379852; 12116222; 12177367; 11889467; 12689911;14722918; 15200506; 15850492; 17082467; 17664401; 17668384; 18462864; 19439424; 19738637; 21108397; 21426321; 22490986; 22585566; 22922607; 23039062; 23072184; 26029707; 31400578 ASAH1 735 427 Farber lipogranulomatosis; Spinal muscular atrophy with progressive myoclonic epilepsy AR N/A N/A Biochemical; Musculoskeletal; Neurologic; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13859108; 6423791; 2983648; 2854742; 3103372; 3130860; 8955159; 8892023; 11241842; 22703880; 24164096 ASB10 17185 136371 Glaucoma 1, open angle, F AD Adult Ophthalmologic Ophthalmologic Open-angle glaucoma is typically asymptomatic until late stages, when irreversible nerve damage has already taken place; Agents that may contribute to glaucoma should be avoided 22156576 ASCC1 24268 51008 Barrett esophagus/Esophageal adenocarcinoma AD Adult Allelic with Spinal muscular atrophy with congenital bone fractures 2 (AR) Gastrointestinal; Musculoskeletal; Neurologic; Oncologic Gastrointestinal; Oncologic Awareness of disease risk may allow surveillance, preventive measures (eg, related to Barrett esophagus) and early treatment of malignancy, which may reduce morbidity and mortality 21791690; 26924529; 28218388; 30327447 ASCL1 738 429 Central hypoventilation syndrome, congenital (Haddad syndrome) AD Pediatric Neurologic Neurologic Early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality 14532329 ASH1L 19088 55870 Mental retardation, autosomal dominant, 52 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23033978; 25961944; 27824329; 28191889; 28394464 ASIP 745 434 Skin/hair/eye pigmentation 9 AD N/A N/A Dermatologic General The clinical relevance is unclear, though variants may be related to susceptibility to melanoma 11833005; 18488028 ASL 746 435 Argininosuccinic aciduria AR Pediatric Biochemical; Dermatologic; Neurologic Biochemical; Pharmacogenomic Dietary and medical therapy (eg, with low-protein diet supplemented with arginine), may be beneficial, and special care to prevent/treat acute metabolic decompensation (eg, with IV glucose and ammonia-reducing agents) may be effective; Certain agents (such as enflurane, an anesthetic agent) should be avoided due to reports of adverse reactions 13503250; 5836520; 84150; 2263616; 1897577; 1594374; 9504797; 12408190; 12384776; 17326097; 22541557; 20236848; 19635676; 22541557; 22841516; 23040521; 25135652 ASNS 753 440 Asparagine synthetase deficiency AR Pediatric Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24139043; 27469131; 28776279; 29279279 ASPA 756 443 Aspartoacylase deficiency (Canavan disease) AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2512436; 8252036; 8023850; 10909858; 12638939; 16437572; 18070137 ASPH 757 444 Facial dysmorphism, lens dislocation, anterior segment abnormalities, and spontaneous filtering blebs AR Pediatric Craniofacial; Ophthalmologic Ophthalmologic Early surgical removal of the lens has been reported as necessary in order to preserve visual function by preventing irreversible corneal and trabecular meshwork damage 11241487; 23687502; 24768550 ASPM 19048 259266 Microcephaly, primary autosomal recessive, 5 AR N/A N/A Neurologic General Frequent infections have been described, but it is not clear if these are intrinsic to the disorder or secondary to neurologic manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12355089; 14574646; 16673149; 18452193; 19353628; 19028728; 19770472 ASPRV1 26321 151516 Ichythosis, lamellar, autosomal dominant AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32516568 ASS1 758 445 Citrullinemia AR Pediatric Biochemical; Gastrointestinal; Neurologic Biochemical; Pharmacogenomic To prevent decompensation, medical therapy (eg, with sodium phenylbutyrate, L-carnitine) and dietary management (including avoidance of excess protein) can be beneficial, especially in high-risk states such as during infectious episodes; In the acute state, control of hyperammonemia (eg, with sodium benzoate/phenylacetate or emergent hemodialysis, with dietary measures to prevent catabolism) with steps to prevent increased intracranial pressure can be beneficial; Avoidance of certain agents (eg, valproate) is warranted due to potential adverse events 934749; 6807193; 3459354; 2358466; 3148074; 2246861; 7977368; 7557970; 11571557; 11804205; 11941481; 15334737; 15266621; 19006241; 20142522; 20301631; 22494546; 22594780; 22768672; 23099195; 23246278; 23430935; 23611581; 25135652 ASXL1 18318 171023 Bohring-Opitz syndrome AD N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21706002; 22419483 ASXL2 23805 55252 Shashi-Pena syndrome AD N/A N/A Cardiovascular; Craniofacial; Endocrine; Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27693232 ASXL3 29357 80816 Bainbridge-Ropers syndrome AD N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23383720 ATAD1 25903 84896 Hyperekplexia 4 AR Pediatric Neurologic Neurologic The condition can include severe neurologic sequelae, and medical management (with perampanel, an AMPAR antagonist) has been reported as having some benefits in individuals 28180185; 29390050; 29659736 ATAD3A 25567 55210 Harel-Yoon syndrome; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal AD/AR N/A N/A Biochemical; Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic; Neurologic; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27640307; 28549128; 29053797 ATCAY 779 85300 Ataxia, cerebellar, Cayman type AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14556008 ATF6 791 22926 Achromatopsia 7 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26029869; 26063662 ATIC 794 471 AICA-ribosuria due to ATIC deficiency AR N/A N/A Biochemical; Craniofacial; Dermatologic; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15114530; 32557644 ATL1 11231 51062 Neuropathy, hereditary sensory, type 1D; Spastic paraplegia 3, autosomal dominant AD N/A N/A Neurologic General Congenital insensitivity to pain can result in injuries and infections Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11685207; 12112092; 15517445; 15596607; 16401858; 16533974; 17502470; 21194679; 21336785; 24473461 ATL3 24526 25923 Neuropathy, hereditary sensory, type IF AD N/A N/A Neurologic General Insensitivity to pain can result in injuries and infections Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24459106; 30680846 ATM 795 472 Breast cancer, susceptibility to; Ataxia-Telangiectasia AD/AR Pediatric (Ataxia-Telangiectasia); Adult (Breast cancer, susceptibility to) Allergy/Immunology/Infectious; Neurologic; Oncologic; Ophthalmologic Allergy/Immunology/Infectious; Oncologic Though the evidence is overall difficult to interpret, heterozygotes may be at increased risk of a number of types of malignancies For breast cancer, susceptibility to, awareness of the risk of malignancy may allow surveillance, preventive measures, and early diagnosis and treatment; In Ataxia-Telangiectasia, for infectious complications, prophylaxis and early and aggressive treatment of infections can be beneficial; Surveillance for malignancy can be beneficial; Precautions should be taken related to ionizing radiation and chemotherapeutic regimens (eg, related to dosage) 311128; 4515676; 4132004; 310962; 7124732; 3496017; 3785360; 3788973; 3574400; 2916583; 2136770; 2253179; 2005780; 1961222; 1304718; 1377828; 8365732; 7836845; 7792600; 8976369; 9054927; 9259193; 9054948; 9463314; 10571946; 10425038; 9887333; 10677309; 10980530; 11826028; 12226795; 12552559; 15942625; 16864838; 16832357; 19535770; 19440741; 20301790; 21429505; 23264026; 23612382; 23900766; 25186627; 25330149 ATN1 3033 1822 Congenital hypotonia, epilepsy, developmental delay, and digital anomalies; Dentatorubro-pallidoluysian atrophy AD N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6808417; 2742549; 7951323; 8136840; 8041369; 7477999; 8644735; 9568927; 11160976; 15948186; 30827498 ATOH7 13907 220202 Persistent hyperplastic primary vitreous, autosomal recessive AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9677055; 21441919; 21474777; 22068589; 22645276 ATP11C 13554 286410 Hemolytic anemia, congenital, X-linked XL N/A N/A Hematologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26944472 ATP13A2 30213 23400 Kufor-Rakeb syndrome (Parkinson disease 9) AR Pediatric Allelic with Ceroid lipofuscinosis, neuronal, 12 (AR); Spastic paraplegia, autosomal recessive, 78 (AR) Neurologic Neurologic In Kufor-Rakeb syndrome, response to levodopa has been documented 16964263; 17485642; 20310007; 22388936; 27217339 ATP1A1 799 476 Hypomagnesemia, seizures, and mental retardation 2 AD Pediatric Allelic with Charcot-Marie-Tooth disease, axonal, type 2DD (AD) Neurologic; Renal Renal The condition can include renal salt wasting, and awareness may allow prompt management (however, seizures have been noted to persist despite magnesium supplementation) 29499166; 30388404 ATP1A2 800 477 Alternating hemiplegia of childhood 1; Migraine, familial hemiplegic 2 AD Pediatric Neurologic Neurologic; Pharmacogenomic In Alternating hemiplegia of childhood, medical treatment (with calcium channel blockers) has been described as at least partially effective; Vasoconstricting agents (due to risk of stroke) and cerebral angiograophy (due to risk of precipitation of attack) should be avoided 9579893; 12539047; 12953268; 14667076; 14636773; 14636773; 15159495; 15174025; 15210532; 15286158; 15459825; 15985592; 16437583; 16344534; 16538223; 17142831; 17473835; 18056581; 18028456; 18846413; 20301562; 20837964; 21352219; 22759692; 23203776; 23838748; 23918834 ATP1A3 801 478 Alternating hemiplegia of childhood 2; Dystonia 12; Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome AD Pediatric Allelic with Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome (AD) Audiologic/Otolaryngologic; Cardiovascular; Neurologic; Ophthalmologic Cardiovascular; Neurologic In Alternating hemiplegia of childhood 2, medical treatment with calcium channel blockers has been described as beneficial (though not curative) for treatment of the hemiplegic attacks in the majority of individuals patients; Individuals with ATP1A3-related disorders have been described with arrhthymias, and awareness may allow surveillance and management (eg, with ICD or pacemaker placement); In Dystonia 12, reports indicate limited efficacy of levodopa treatment 8733056; 15260953; 17282997; 19652145; 20558373; 22842232; 22850527; 22857851; 22924536; 23409136; 24468074; 24842602; 25056583; 32913013 ATP2A1 811 487 Brody myopathy AR Pediatric Musculoskeletal Musculoskeletal Individuals typically present with exercise-induced muscle relaxation impairment, with, stiffening, cramps, and muscle pain, and medical management (eg, with dantrolene or verapamil) has been described as beneficial in some individuals 1405485; 8040329; 8841193; 9367679; 10914677; 20142766 ATP2A2 812 488 Darier-White disease; Acrokeratosis verruciformis (Hopf disease) AD N/A N/A Dermatologic General In Darier-White disease, oral retinoids may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 921905; 1619075; 10441324; 10080178; 10441323; 11121153; 12542527; 12925205; 14675181; 22004489; 22035154; 22329366; 22814319; 22909361 ATP2B3 816 492 Spinocerebellar ataxia, X-linked 1 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10797423; 22912398 ATP2C1 13211 27032 Benign chronic pemphigus AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4939904; 5093171; 3978039; 2528572; 1554604; 1575528; 10615129; 15545997; 21623880; 21883398; 22124882; 22229453; 22607350; 22788811 ATP5F1A 823 498 Combined oxidative phosphorylation deficiency 22; Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4 AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23596069; 23599390 ATP5F1E 838 514 Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18953340; 20566710 ATP5MK 30889 84833 Mitochondrial complex V (ATP synthase) deficiency, nuclear type 6 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29917077 ATP6AP1 868 537 Immunodeficiency 47 XL Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Gastrointestinal; Neurologic Allergy/Immunology/Infectious Among other features, individuals may have infantile-onset severe infections (and hypogammaglobulinemia) and awareness may allow preventive measures and early and aggressive treatment of infections 27231034; 29396028; 32058063; 32216104 ATP6AP2 18305 10159 Parkinsonism with spasticity, X-linked; Congenital disorder of glycosylation, type IIr XL Pediatric Allelic with Mental retardation, X-linked, syndromic, Hedera type (XL) Allergy/Immunology/Infectious; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Hematologic; Neurologic The evidence of variants being related to disease causation for some conditions has been questioned due to subsequent population-based studies In Parkinsonism, response to l-dopa has been reported; In Congenital disorder of glycosylation, type IIr, individuals have been described with recurrent infections, and awareness may allow early diagnosis and early and aggressive treatment of infections; In Congenital disorder of glycosylation, type IIr, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 11782983; 15746149; 20629132; 23595882; 23871722 ATP6V0A2 18481 23545 Cutis laxa, autosomal recessive, type IIA; Wrinkly skin syndrome AR N/A N/A Biochemical; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15657616; 18157129; 17971833; 19401719; 22773132 ATP6V0A4 866 50617 Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss AR Pediatric Audiologic/Otolaryngologic; Renal Renal The condition can involve electrolyte abnormalities, and medical management of these (eg, with alkali replacement) can reverse most biochemical abnormalities, and may be effective, especially in severe cases, to prevent eventual renal insufficiency 10973252; 12414817 ATP6V1A 851 523 Cutis laxa, autosomal recessive, type IID AR Pediatric Allelic with Developmental and epileptic encephalopathy 93 (AD) Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular The condition can include early-onset cardiomyopathy, and awareness may allow early diagnosis and management 24459010; 28065471; 29668857 ATP6V1B1 853 525 Renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss AR Pediatric Audiologic/Otolaryngologic; Renal Renal Individuals can present in infancy with acute with dehydration (which can be lethal), which can be prevented by early recognition 9916796; 12414817; 12566520; 16433694; 18798332 ATP6V1B2 854 526 Deafness, congenital, with onychodystrophy, autosomal dominant; Zimmermann-Laband syndrome 2 AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 18541964; 23994350; 24913193; 25915598 ATP6V1E1 857 529 Cutis laxa, autosomal recessive, type IIC AR Pediatric Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal Cardiovascular The condition can include early-onset cardiomyopathy, and awareness may allow early diagnosis and management 28065471 ATP7A 869 538 Menkes disease XL Pediatric Allelic with Occipital horn syndrome (XL); Spinal muscular atrophy, distal, X-linked 3 (XL) Biochemical; Cardiovascular; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal Biochemical; Renal With early diagnosis, daily copper injections may be beneficial (SQ injections before 10 days of life have been reported as resulting in improvement of neurologic outcome); Individuals may be prone to urinary tract infections, and measures such as antibiotic prophylaxis may be beneficial 14472668; 5045346; 1218238; 953234; 6104292; 6140952; 4075564; 2839049; 2512453; 8490646; 8490647; 8490659; 8099605; 7842019; 8149649; 7887410; 8923001; 8528242; 9111998; 9138147; 9511979; 9894833; 14635105; 14985388; 15981243; 16630173; 17108763; 18256395; 19153371; 20652413; 20301586; 20170900; 22992316; 22711717; 22695177; 21221114 ATP7B 870 540 Wilson disease AR Pediatric Biochemical; Gastrointestinal; Neurologic; Ophthalmologic Biochemical; Gastrointestinal Dietary measures (eg, avoidance of copper-containing foods), as well as medications (eg, penicillamine, zinc, vitamin B6, tetrathiomolybdate), and possible liver transplant, can be beneficial 463930; 3900322; 3561699; 3328213; 8298639; 8298641; 8201263; 7884606; 8610495; 9794697; 10435491; 10435489; 10673307; 12376745; 12633149; 12756138; 16283883; 16216950; 20301685; 16606763; 21901655; 22327203; 21832955; 22083169 ATP8A2 13533 51761 Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22892528 ATP8B1 3706 5205 Familial intrahepatic cholestasis, recurrent; Cholestasis, progressive familial intrahepatic 1; Intrahepatic cholestasis of pregnancy AD/AR Pediatric Allelic with Benign recurrent intrahepatic cholestasis (AD/AR) Gastrointestinal; Obstetric Gastrointestinal; Obstetric In severe forms, specific nutritional care may be beneficial (eg, including specific vitamin E supplementation); Hepatic manifestations may result in death in adolescence/early adulthood without surgical intervention; In pregnancy, Cholestasis, familial intrahepatic, of pregnancy, can cause severe sequelae (including death) in the fetus, as well as adverse maternal health outcomes, and precautions, including early delivery may be beneficial 13840084; 5807632; 5762004; 5049818; 1218817; 3564958; 8088298; 7912266; 9500542; 9918928; 11093741; 15239083; 15448432; 15888793; 15657619; 20301474 ATPAF2 18802 91647 Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1 AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14757859; 20566710 ATR 882 545 Cutaneous telangiectasia and cancer syndrome, familial; Seckel syndrome 1 AD/AR Pediatric Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Oncologic Oncologic Though both Seckel syndrome 1 and Cutaneous telangiectasia and cancer syndrome, familial are potentially recognizable, surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of oncologic manifestations, which may reduce morbidity and mortality 13869653; 6022184; 4378248; 7046443; 8358044; 8182723; 9128935; 10889046; 12640452; 22341969; 23111928; 30199583; 30846821 ATRX 886 546 Alpha-thalassemia/mental retardation syndrome; Mental retardation-hypotonic facies syndrome, X-linked XL N/A N/A Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6267462; 6682021; 6711605; 3239563; 1684092; 7726225; 8644709; 10398237; 10398234; 11449489; 11050622; 10751095; 15508018; 16222662; 16100724; 16813605; 16955409; 16688741; 17579672; 19764021; 20301622; 22089611 ATXN1 10548 6310 Spinocerebellar ataxia 1 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8275090; 8358429; 7951322; 8198139; 8037204; 8615077; 10424816; 11973625; 14967775; 16133185; 15747371; 18262566; 18685131; 20301363 ATXN10 10549 25814 Spinocerebellar ataxia 10 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11017075; 11506407; 15127363; 16717236; 17420323; 20301354; 20818609; 21236683; 21531163 ATXN2 10555 6311 Spinocerebellar ataxia 2 AD N/A N/A Neurologic General In some individuals, the phenotype may include L-dopa responsive parkinsonism; Homozygosity/compound heterozygosity has been reported Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8896557; 8896555; 8896556; 10735276; 9779806; 10993999; 11761482; 12210804; 12451209; 12671950; 15254952; 14732617; 15747371; 17568014; 17923635; 19676102; 20301452; 21610160; 21562247; 21880993; 21934711 ATXN3 7106 4287 Spinocerebellar ataxia 3 (Machado-Joseph disease) AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5061839; 865531; 7874163; 7573040; 7496771; 7795637; 7633439; 7561932; 7655453; 8619527; 8640226; 9403486; 11176969; 15457499; 15747371; 20301375; 21555642; 21635785; 22023810 ATXN7 10560 6314 Spinocerebellar ataxia 7 AD N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7477379; 8908515; 9288099; 9536097; 9736784; 10330346; 10453742; 11030806; 15349877; 15750685; 15747371; 20301433; 23368522 ATXN8 32925 724066 Spinocerebellar ataxia 8 AD N/A N/A Neurologic; Ophthalmologic General The causative expansion variant is located in both the ATXN8OS 3' UTR and a polyglutamine ORF in ATXN8 Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16804541 ATXN8OS 10561 6315 Spinocerebellar ataxia 8 AD N/A N/A Neurologic; Ophthalmologic General The causative expansion variant is located in both the ATXN8OS 3' UTR and a polyglutamine ORF in ATXN8 Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10192387; 14756671; 16804541; 19680539; 20301445; 20403608 AUH 890 549 3-methylglutaconic aciduria, type I AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Dietary measures (leucine restriction) have been suggested Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 720359; 3082934; 1710267; 1375542; 9762598; 10070612; 12434311; 15033206; 16354225; 17130438; 20855850; 21840233; 23296368 AURKC 11391 6795 Spermatogenic failure 5 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17435757; 19147683; 21733974; 22888167 AUTS2 14262 26053 Mental retardation, autosomal dominant 26 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22872102; 23332918; 25205402 AVIL 14188 10677 Nephrotic syndrome, type 21 AR N/A N/A Renal General Renal transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29058690 AVP 894 551 Diabetes insipidus, neurohypophyseal AD/AR Pediatric Endocrine; Renal Endocrine; Renal Treatment/prevention of hypernatremia can be effective; Medications related to osteoporosis/osteopenia may be beneficial 10404801; 10369876; 14673472; 15070970; 22524462 AVPR2 897 554 Diabetes insipidus, nephrogenic, X-linked; Nephrogenic syndrome of inappropriate antidiuresis XL Pediatric Endocrine; Renal Endocrine; Renal In Diabetes insipidus, nephrogenic, X-linked, sequelae may be prevented with early genetic knowledge to allow management of electrolyte and fluid balances (eg, with specific diuretics) has been reported as potentially beneficial); In Nephrogenic syndrome of inappropriate antidiuresis, patients can have electrolyte and fluid imbalances, and management of these issues through initial fluid restriction and osmotic agents) have been reported to be beneficial 13644230; 3970081; 3080575; 1356229; 1303271; 8104196; 9329382; 10477148; 15872203; 16845277; 22722264 AXIN1 903 8312 Caudal duplication anomaly AD/Methylation N/A N/A Gastrointestinal; Genitourinary; Musculoskeletal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12376942; 16773576 AXIN2 904 8313 Oligodontia-colorectal cancer syndrome AD Adult Allelic with Oligondontia, isolated (AD) Dental; Oncologic Oncologic Some individuals appear to have dental anomalies without obviously increased colorectal cancer risk Although the condition may be clinically recognizable in many individuals, the oncologic risk may not be clear, and awareness may allow surveillance for and early treatment of related malignancies (eg, breast cancer, colorectal cancer), which may reduce morbidity and mortality 15042511; 21626677; 21416598 B2M 914 567 Immunodeficiency 43 AR Pediatric Allelic with Amyloidosis, systemic visceral (AD) (In amyloidosis, liver transplantation may be beneficial, but it is not clear if early (genetic) diagnosis would be beneficial) Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Neurologic; Renal Allergy/Immunology/Infectious Individuals can have immunodeficiency, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 4186801; 2254461; 16549777; 22693999; 25702838 B3GALNT1 918 8706 Blood group, globoside system; Blood group, P1PK system BG Pediatric Hematologic; Neurologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 12023287 B3GALNT2 28596 148789 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 11 AR N/A N/A Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23453667 B3GALT6 17978 126792 Ehlers-Danlos syndrome, spondylodysplastic type, 2; Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures; Al-Gazali syndrome AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23664117; 23664118; 25149931; 29443383 B3GAT3 923 26229 Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21763480; 24668659 B3GLCT 20207 145173 Peters-plus syndrome AR Pediatric Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic Ophthalmologic Individuals may be at high risk for ophthalmologic complications, including glaucoma, and surveillance may allow early interventions and management 16909395; 18199743; 18798333; 19796186; 20301637; 21067481; 21671750; 22759511 B4GALNT1 4117 2583 Spastic paraplegia 26, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23746551 B4GALT1 924 2683 Congenital disorder of glycosylation, type IId AR Pediatric Biochemical; Hematologic; Gastrointestinal; Musculoskeletal; Neurologic; Renal Hematologic; Gastrointestinal Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery; Individuals have been described with hepatosplenomegaly and transient cholestatic jaundice, which was treated with ursodeoxycholic acid 11901181; 11930273; 21920538; 32157688 B4GALT7 930 11285 Ehlers-Danlos syndrome, spondylodysplastic type, 1 AR N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3631078; 10473568; 10506123; 15211654; 16583246; 20809901; 24755949 B4GAT1 15685 11041 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23359570 B9D1 24123 27077 Joubert syndrome 27; Meckel syndrome 9 AR N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21493627; 24886560 B9D2 28636 80776 Meckel syndrome 10 AR N/A N/A Gastrointestinal; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21763481 BAAT 932 570 Hypercholanemia, familial; Bile acid conjugation defect 1 AR Pediatric Gastrointestinal; Hematologic Gastrointestinal; Hematologic Individuals with Hypercholanemia may present with manifestations including pruritus, sequelae of fat malabsorption (which can be severe), and elevated serum bile acid concentrations, which typically respond to medical treatment (eg, with ursodeoxycholic acid and fat-soluble vitamins); Individuals with Bile acid conjugation defect , which can include janudice, failure to thrive, rickets, growth deficiency, and coagulopathy, have been reported as responding to medical management (eg, with ursodeoxycholic acid, FFP and vitamin K); Liver transplant has been described 12704386; 22783059; 23415802 BACH2 14078 60468 Immunodeficiency 60 AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may manifest with findings such as inflammatory bowel disease and recurrent sinopulmonary infections and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 28530713 BAG3 939 9531 Cardiomyopathy, dilated, 1HH; Myopathy, myofibrillar 6 AD Adult Cardiovascular; Musculoskeletal; Neurologic Cardiovascular In Dilated cardiomyopathy, surveillance (eg, with echocardiogram and electocardiogram) may allow early detection and management of manifestations, which may be beneficial; In Myofibrillar myopathy, individuals typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD); Cardiac transplantation may be necessary individuals with severe forms of cardiomyopathy; Heart transplant has been described 16936253; 19085932; 20301672; 21898660; 21256014; 21353195; 21361913; 21459883; 25208129 BANF1 17397 8815 Nestor-Guillermo progeria syndrome AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21932319; 21549337 BAP1 950 8314 Tumor predisposition syndrome AD Pediatric Dermatologic; Oncologic Dermatologic; Oncologic Awareness of oncologic risk may allow surveillance for and early treatment of a variety of malignancies (including uveal and cutaneous melanomas, mesothelioma, and several other types of cancer), which may reduce morbidity and mortality 21941004; 21874000 21874003; 23032617; 23341325 BARD1 952 580 Breast cancer, susceptibility to AD Adult Oncologic Oncologic Though the availability of empirical data is incomplete as applies to both screening strategies and prophylactic treatment, surveillance may allow early detection and management of cancer 14550946; 16768547; 16825437; 17333333; 24549055; 25058500 BBIP1 28093 92482 Bardet-Biedl syndrome 18 AR N/A N/A Gastrointestinal; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24026985 BBS1 966 582 Bardet-Biedl syndrome 1 AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Variants may modify the severity of BBS and related disorders due to variants in other BBS-associated genes Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12118255; 12567324; 12677556; 12837689; 12524598; 15314642; 20120035; 20301537; 22410627; 22773737; 22940089; 23143442 BBS10 26291 79738 Bardet-Biedl syndrome 10 AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Variants may modify the severity of BBS and related disorders due to variants in other BBS-associated genes Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16823392; 16582908; 20120035; 20301537; 20805367; 22410627; 25982971 BBS12 26648 166379 Bardet-Biedl syndrome 12 AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Variants may modify the severity of BBS and related disorders due to variants in other BBS-associated genes Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17160889; 20827784; 20120035; 20301537; 22410627; 25982971 BBS2 967 583 Bardet-Biedl syndrome 2; Retinitis pigmentosa 74 AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Variants may modify the severity of BBS and related disorders due to variants in other BBS-associated genes Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8298649; 11285252; 11567139; 16823392; 16582908; 20120035; 20301537; 20618352; 22410627; 25541840 BBS4 969 585 Bardet-Biedl syndrome 4 AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Variants may modify the severity of BBS and related disorders due to variants in other BBS-associated genes Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7711739; 11381270; 12016587; 15654695; 20301537; 22219648 BBS5 970 129880 Bardet-Biedl syndrome 5 AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Variants may modify the severity of BBS and related disorders due to variants in other BBS-associated genes Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15137946; 18203199; 20301537; 22410627; 25982971 BBS7 18758 55212 Bardet-Biedl syndrome 7 AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Variants may modify the severity of BBS and related disorders due to variants in other BBS-associated genes Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12567324; 21937992; 20301537; 22410627 BBS9 30000 27241 Bardet-Biedl syndrome 9 AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Variants may modify the severity of BBS and related disorders due to variants in other BBS-associated genes Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16380913; 20301537 BCAM 6722 4059 Blood group, Lutheran system; Blood group, Auberger system; Blood group, Lutheran null BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 14025138; 4836779; 1146276; 9192786; 9166867; 17319831; 18487511 BCAP31 16695 10134 Deafness, dystonia, and cerebral hypomyelination XL N/A N/A Audiologic/Otolaryngologic; Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24011989 BCAT2 977 587 Hypervalinemia and hyperleucine-isoleucinemia AR Pediatric Biochemical Biochemical An individual has been described with clinical and radiological neurologic abnormalities, and biochemical management (eg, with pharmacologic doses of B6) have been reported as yielding clinical and biochemical benefits 25653144 BCHE 983 590 Butyrlcholinesterase deficiency AR Pediatric Biochemical Pharmacogenomic Individuals have prolonged apnea upon use of specific anesthetics (ie, suxamethonium, succinylcholine) 13711731; 14465122; 4984470; 3741370; 3225823; 2915989; 2911599; 2013061; 1662391; 1349196; 1415224; 8554068; 9543549; 9302273; 9110359; 9388484; 10190327; 10699053; 12881446; 16788378; 18075469; 18555211; 21029050 BCKDHA 986 593 Maple syrup urine disease, type Ia AR Pediatric Biochemical; Neurologic Biochemical Dietary measures (eg, leucine restriction, high-calorie branched chain amino acid-free formulas, isoleucine and valine supplementation) combined with careful surveillance can be beneficial to prevent decompensation and minimize disease sequelae; specific treatment in times of metabolic decompensation can reduce morbidity and mortaility; Liver transplantation is effective for classic MSUD; Specific monitoring is indicated in pregnancy 8037208; 7883996; 7672509; 11112664; 12042535; 14567968; 14742428; 17922217; 18378174; 20301313; 20301495; 20061171; 22326532 BCKDHB 987 594 Maple syrup urine disease, type Ib AR Pediatric Biochemical; Neurologic Biochemical Dietary measures (eg, leucine restriction, high-calorie branched chain amino acid-free formulas, isoleucine and valine supplementation) combined with careful surveillance can be beneficial to prevent decompensation and minimize disease sequelae; specific treatment in times of metabolic decompensation can reduce morbidity and mortaility; Liver transplantation is effective for classic MSUD; Specific monitoring is indicated in pregnancy 2022752; 11509994; 11112664; 14567968; 17922217; 20301495; 22326532 BCKDK 16902 10295 Branched-chain ketoacid dehydrogenase kinase deficiency AR Pediatric Biochemical; Neurologic Biochemical Individuals may present with features such as autism and epilepsy, and though not definitely proven, there is strong evidence that dietary supplementation (eg, with branched chain amino acids) may be beneficial 22956686 BCL10 989 8915 Immunodeficiency 37 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described as susceptible to severe infections, and awareness may allow preventive measures and early and aggressive treatment of infections 25365219 BCL11A 13221 53335 Dias-Logan syndrome AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24810580; 27453576 BCL11B 13222 64919 Immunodeficiency 49; Intellectual developmental disorder with speech delay, dysmorphic facies, and T-cell abnormalities AD Pediatric Allergy/Immunology/Infectious; Craniofacial; Dental; Dermatologic; Neurologic; Musculoskeletal Allergy/Immunology/Infectious Among other features, individuals have been described as susceptible to severe or frequent infections, and awareness may allow preventative measures and early and aggressive treatment of infections; In Immunodeficiency 49, HSCT has been described 27959755; 29985992 BCO1 13815 53630 Hypercarotenemia and vitamin A deficiency, autosomal dominant AD Pediatric Biochemical Biochemical; Gastrointestinal Dietary precautions may be beneficial, as individuals may have manifestations of hypercarotenemia/hypovitaminosis A with a carotenoid-containing/retinol-inadequate diet 5453458; 17951468 BCOR 20893 54880 Microphthalmia, syndromic 2 (Oculofaciocardiodental syndrome) XL N/A N/A Cardiovascular; Craniofacial; Dental; Gastrointestinal; Genitourinary; Ophthalmologic; Musculoskeletal; Renal General The condition can involve multiple congenital anomalies The condition can include cardiovascular, renal, and other anomalies; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13963827; 1225823; 10069716; 15004558; 15770227; 15957158; 20301694; 21740180; 22301464 BCORL1 25657 63035 Shukla-Vernon syndrome XL N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24123876; 30941876 BCR 1014 613 CML treatment, response to AD Pediatric General Pharmacogenomic Variants may confer resistance to certain medications (eg, dasatinib); Certain variants appear to confer STI571 resistance in CML treatment 11423618; 12654249; 14534339; 17684099 BCS1L 1020 617 Bjornstad syndrome AR Pediatric Allelic with GRACILE syndrome (AR); Leigh syndrome (AR); Mitochondrial complex III deficiency, nuclear type 1 (AR), in which some treatment attempts (eg, with apotransferrin) have been reported, and treatment with "mitochondrial cocktail" type therapy may be beneficial Audiologic/Otolaryngologic; Biochemical; Dermatologic; Gastrointestinal; Genitourinary; Neurologic; Ophthalmologic; Renal Audiologic/Otolaryngologic The condition includes frequently recognizable features such as hair anomalies (pili torti) Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; It has been suggested that that stapes surgery should not be performed due to a high likelihood of complications (the use of cochlear implants has been reported as beneficial) 9482441; 10654962; 7577396; 10654962; 11528392; 12215968; 12910490; 17314340; 17403714; 19162478; 19389488; 19508421; 20580947; 20518024; 20472482; 22277166; 22991165 BDNF 1033 627 Central hypoventilation syndrome, congenital AD Pediatric Neurologic Neurologic Early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality 10390427; 11840487; 20301600 BDP1 13652 55814 Deafness, autosomal recessive 112 AR N/A N/A Audiologic/Otolaryngologic General Hearing loss has been described as postlingual Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24312468 BEAN1 24160 146227 Spinocerebellar ataxia 31 AD N/A N/A Audiologic/Otolaryngologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17611710; 19878914 BEST1 12703 7439 Vitreoretinochoroidopathy AD Adult Allelic with Macular dystrophy, vitelliform, adult-onset (AD); Retinitis pigmentosa 50 (AD); Macular dystrophy, vitelliform 2 (AD); Best macular dystrophy (AD); Bestrophinopathy, autosomal recessive (AR) Ophthalmologic Ophthalmologic; Pharmacogenomic Findings such as glaucoma and retinal detachment have been described, and surveillance and early treatment (eg, direct laser photocoagulation and anti-vascular endothelial growth factors for choroidal neovascularization and hemorrhage), as well as preventive measures, may be beneficial; Agents that may contribute to glaucoma, as well as smoking, should be avoided 13546939; 838599; 7065944; 6689931; 8431155; 9662395; 10453731; 10331951; 10854112; 10737974; 11585313; 12543751; 15452077; 16458719; 16678511; 17698758; 17591911; 18179881; 18611979; 19853238; 20057903; 20301346; 20375334; 20847757; 21192766; 21320969; 22422030; 22584882; 22633354; 23290749; 23572118; 23765342; 23823511; 24345323 BFSP1 1040 631 Cataract 33 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17225135 BFSP2 1041 8419 Cataract 12, multiple types AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10729115; 10739768; 10634598; 15570218; 17982427; 18958306; 21836522 BGN 1044 633 Meester-Loeys syndrome XL Pediatric Allelic with Spondyloepimetaphyseal dysplasia, X-linked (XL) Cardiovascular; Craniofacial; Musculoskeletal; Neurologic Cardiovascular Among other features, the condition can include early-onset aortic aneurysm, and awareness may allow erly diagnosis and management 8064814; 27236923; 27632686 BHLHA9 35126 727857 Camptopolysyndactyly, complex; Syndactyly, mesoaxial synostotic, with phalangeal reduction AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9783716; 10096595; 15039974; 15779011; 25466284; 27041388 BHLHE41 16617 79365 Short sleeper, familial natural, 1 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19679812 BICC1 19351 80114 Renal dysplasia, cystic, susceptibility to AD Pediatric Renal Renal Sequelae can include vesicoureteral reflux, and early diagnosis could be helpful to institute measures to preserve kidney function 21922595 BICD2 17208 23299 Spinal muscular atrophy, lower extremity-predominant, 2A, childhood onset, autosomal dominant; Spinal muscular atrophy, lower extremity-predominant, 2B, prenatal onset, autosomal dominant AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23664116; 23664119; 23664120; 27751653; 28635954; 30054298 BIN1 1052 274 Myopathy, centronuclear, 2 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17676042; 20142620; 22392505 BLK 1057 640 Maturity-onset diabetes of the young, type 11 AD N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19667185 BLM 1058 641 Bloom syndrome AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Pulmonary Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Oncologic Variants may also be related to risk of malignancy in the general poulation Surveillance and early diagnosis of malignancy could potentially be beneficial; Avoidance of ionizing radiation/DNA-damaging chemicals (as well as sun exposure) can reduce morbidity; Individuals may be susceptible to infections, and prompt treatment, as well as control of gastroesophageal reflux, which can be contributory, can be beneficial 5923432; 7386453; 7273457; 6705251; 3040954; 3808032; 3808031; 2721026; 1809225; 7585968; 8875252; 9062585; 9285778; 10464606; 11477604; 12242432; 15137905; 17407155; 18471088; 18974064; 20301572; 21815139; 22514588; 23028338; 23443610; 24118499 BLNK 14211 29760 Agammaglobulinemia 4 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals can have immunodeficiency (which can involve frequent and severe infections, including reports of lethal bacterial sepsis) related to agammaglobulinemia, and antiinfectious prophylaxis (IVIG has been reported to be beneficial) and early and aggressive treatment of infections may be beneficial 10583958 BLOC1S3 20914 388552 Hermansky-Pudlak syndrome 8 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic Allergy/Immunology/Infectious; Dermatologic; Hematologic; Ophthalmologic Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Surveillance related to ophthalmologic and other manifestations has been recommended in all individuals with HPS 16385460; 20301464 BLOC1S5 18561 63915 Hermansky-Pudlak syndrome 11 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Hematologic; Ophthalmologic Allergy/Immunology/Infectious; Dermatologic; Hematologic; Ophthalmologic Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Surveillance related to ophthalmologic and other manifestations has been recommended in all individuals with HPS 32565547 BLOC1S6 8549 26258 Hermansky-Pudlak syndrome 9 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic Allergy/Immunology/Infectious; Dermatologic; Hematologic; Ophthalmologic Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Surveillance related to ophthalmologic and other manifestations has been recommended in all individuals with HPS 21665000; 20301464; 22461475 BLVRA 1062 644 Hyperbiliverdinemia AD/AR N/A N/A Gastrointestinal General Appropriate hepatic-related care may be beneficial, but the advantage of genetic diagnosis is unclear; Individuals with heterozygous variants have been reported as manifesting with clinical signs in the context of (apparently unrelated) liver dysfunction Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19580635; 19699374; 21278388 BMP1 1067 649 Osteogenesis imperfecta, type XIII AR N/A N/A Craniofacial; Musculoskeletal; Ophthalmologic General The use of bisphosphonates has been described, but it is unclear if an early (genetic) diagnosis would be advantageous Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22052668; 22482805 BMP15 1068 9210 Ovarian dysgenesis 2 XL Pediatric Endocrine; Genitourinary; Obstetric Obstetric Genetic knowledge may allow reproductive capabilities such as via egg preservation 15136966; 16508750; 19263482 BMP2 1069 650 Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 AD Pediatric Allelic with Brachydactyly, type A2 (AD) Cardiovascular; Craniofacial; Musculoskeletal Cardiovascular Brachydactyly, type A2 involves duplication of a downstream regulatory element of the gene Among other features, the condition can involve arrhythmias, and awareness can allow early diagnosis and management 7390514; 19327734; 21357617; 29198724 BMP4 1071 652 Microphthalmia, syndromic 6; Orofacial cleft 11 AD N/A N/A Craniofacial; Endocrine; Musculoskeletal; Neurologic; Renal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18252212; 18305125; 19249007; 21340693 BMPER 24154 168667 Diaphanospondylodysostosis AR N/A N/A Craniofacial; Musculoskeletal; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20869035; 30006055 BMPR1A 1076 657 Polyposis syndrome, hereditary mixed, 2; Polyposis, juvenile intestinal AD Pediatric Oncologic Oncologic Surveillance (eg, with colonoscopy and endoscopic polypectomy, as well upper endoscopy for symptomatic individuals, and monitoring for sequelae including anemia and rectal bleeding) may be beneficial, though partial/total colectomy/gastrectomy may be indicated in some individuals with a large polyp burden; Indivduals may have a variety of HHT-related vascular complications, including arteriovenous malformations, aortic dilatation, and bleeding diatheses, and surveillance and early intervention related to manifestations (eg, related to thromboembolism or hepatic disease) may decrease morbidity and mortality 5483654; 4544011; 7059958; 3707330; 8037173; 7582207; 11381269; 12136244; 15235019; 16152648; 16525031; 17873119; 20843829; 22171123; 22810475 BMPR1B 1077 658 Acromesomelic dysplasia, Demirhan type; Brachydactyly, type A1, D; Brachydactyly A2; Brachydactyly C/Symphalangism-like phenotype AD/AR N/A N/A Genitourinary; Musculoskeletal General In Acromesomelic dysplasia, Demirhan type, interventions may be beneficial to allow reproductive capacity Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14523231; 15805157; 16957682; 24129431; 25758993; 26105076 BMPR2 1078 659 Pulmonary hypertension, primary 1; Pulmonary venoocclusive disease 1 AD Pediatric Cardiovascular; Pulmonary Cardiovascular; Pharmacogenomic; Pulmonary While prognosis is overall poor, medical therapy (eg, with calcium antagonists, anticoagulants, prostanoids, endothelin receptor antagonists, etc.) may be beneficial, though heart/lung transplantation may be required; Control of complications may be beneficial; Exposure to agents such as fenfluramine has been described as greatly increasing the risk of disease 601742; 1863023; 10903931; 11115457; 10973254; 11015450; 12358323; 12446270; 16429403; 16429395; 15965979; 18356561; 20956135; 19749199; 19713419; 19555857; 21801371 BMS1 23505 9790 Aplasia cutis congenita, nonsyndromic AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23785305 BNC1 1081 646 Premature ovarian failure 16 AD Pediatric Obstetric Obstetric Genetic knowledge may allow reproductive capabilities such as via egg preservation 30010909 BNC2 30988 54796 Lower urinary tract obstruction, congenital AD Pediatric Renal Renal The condition may involve occult urinary tract obstruction, which may manifest as frequent urinary tract infections and other sequelae, leading to renal damage, and awareness may allow interventions to preserve kidney function 31051115 BOLA3 24415 388962 Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia AR N/A N/A Biochemical; Cardiovascular; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11156534; 21944046; 22562699; 24334290 BPGM 1093 669 Erythrocytosis, familial, 8 AD/AR Pediatric Hematologic Hematologic Phlebotomy has been reported as beneficial in individuals with recessive disease involving severe loss of enzymatic function; Other reports indicate that RBC transfusions and splenectomy may be indicated in some individuals 14131784; 5885535; 11947623; 152321; 2542247; 1421379 BPNT2 26019 54928 Chondrodysplasia with joint dislocations, GPAPP type AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21549340; 22903787 BPTF 3581 2186 Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) AD N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28942966 BRAF 1097 673 Noonan syndrome 7; Cardiofaciocutaneous syndrome 1; LEOPARD syndrome 3 AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Cardiovascular; Hematologic; Oncologic The conditions may be frequently clinically recognized due to characteristic facial features as well as other manifestations Surveillance and treatment related tomanifestations such as cardiac anomalies (which include pulmonic stenosis, hypertrophic cardiomyopathy, and arrhythmias) can be beneficial; The disorders can include bleeding diathesis, and recognition and preventive measures (eg, in surgical situations) can be beneficial; Individuals with malignancies (eg, ALL) have been reported, and awareness of increased risk may be beneficial 16474404; 16439621; 17551924; 17483702; 19047498; 18456719; 18042262; 18413255; 19206169; 20301303; 20301365; 20523244; 21349766; 21495173; 22946697 BRAT1 21701 221927 Rigidity and multifocal seizure syndrome, lethal neonatal AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22279524; 23035047; 25319849; 25500575; 26483087; 26494257; 27282546 BRCA1 1100 672 Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S AD/AR Pediatric (Fanconi anemia, complementation group S); Adult (Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4) Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic Allergy/Immunology/Infectious; Hematologic; Oncologic Variants may also predispose to a number of other malignancies For hereditary cancer, though the availability of empirical data is incomplete as applies to both screening strategies and prophylactic treatment, surveillance is based on the age of affected family members (for breast cancer, surveillance includes self-examination as well as regular clinical examinations, mammography, and MRI; for ovarian cancer, screening includes regular pelvic examination, transvaginal ultrasounds with Doppler, and CA-125 measurement; for prostate cancer, screening includes regular rectal examination and PSA measurement); Prophylactic mastectomy and/or oophorectomy, as well as chemoprevention (eg, with tamoxifen) are described; Treatment of breast and ovarian cancer follows standard guidelines (ie, that apply more generally), though, new targeted therapies are under investigation; For individuals with metastatic Prostate cancer, management with PARP-inhibitors has been described as improving progression-free survival; For Fanconi anemia: specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count), and HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 7894491; 7894493; 7545954; 9012404; 9450858; 10441598; 10885351; 11157798; 12036267; 11463009; 11463017; 12023992; 12023993; 12161607; 14569130; 12677558; 17233897; 17307836; 18413374; 18349832; 18762988; 19656774; 19190154; 20216074; 20495085; 21531449; 22317870; 22614657; 23269703; 25472942; 29133208; 31157963 BRCA2 1101 675 Breast-ovarian cancer, familial, susceptibility to; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Fanconi anemia, complementation group D1; Wilms tumor; Medulloblastoma AD/AR Pediatric (Fanconi anemia, complementation group D1); Adult (Breast-ovarian cancer, familial, susceptibility to; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Wilms tumor; Medulloblastoma) Allergy/Immunology/Infectious; Dermatologic; Hematologic; Neurologic; Oncologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Oncologic Variants may also predispose to a number of other malignancies For hereditary breast and ovarian cancer, though the availability of empirical data is incomplete as applies to both screening strategies and prophylactic treatment, surveillance is based on the age of affected family members (for breast cancer, surveillance includes self-examination as well as regular clinical examinations, mammography, and MRI; for ovarian cancer, screening includes regular pelvic examination, transvaginal ultrasounds with Doppler, and CA-125 measurement; for prostate cancer, screening includes regular rectal examination and PSA measurement); Prophylactic mastectomy and/or oophorectomy, as well as chemoprevention (eg, with tamoxifen) are described; Treatment of breast and ovarian cancer follows standard guidelines (ie, that apply more generally), though, new targeted therapies are under investigation; There are little empiric data regarding other cancer types, though awareness may allow early diagnosis and treatment; For individuals with metastatic Prostate cancer, management with PARP-inhibitors has been described as improving progression-free survival; For Fanconi anemia: specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count), and HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 8091231; 8524414; 7597059; 9140390; 10441598; 10807385; 12036267; 11133358; 12065746; 12097290; 12161607; 12023992; 12023993; 14569130; 12556369; 14670928; 15912495; 15948173; 15689453; 16825431; 18264087; 18349832; 18355772; 18413374; 19190154; 21118973; 21593217; 21531449; 20216074; 22614657; 23285130; 31157963 BRDT 1105 676 Spermatogenic failure 21 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28199965 BRF1 11551 2972 Cerebellofaciodental syndrome AR N/A N/A Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25561519 BRIP1 20473 83990 Breast cancer, early onset, susceptibility to; Fanconi anemia, complementation group J AD/AR Pediatric (Fanconi anemia, complementation group J); Adult (Breast cancer) Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management For Breast cancer, awareness may allow early surveillance, preventive measures, and early diagnosis and treatment of disease; For Fanconi anemia, specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 11301010; 14630800; 14983014; 16116424; 16116423; 17033622; 21568838; 21964575; 22006311; 22441895; 23285130 BRPF1 14255 7862 Intellectual disability disorder with dysmorphic facies and ptosis (IDDDFP) AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27939639; 27939640 BRWD3 17342 254065 Mental retardation, X-linked 93 XL N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7943039; 17668385; 19377476 BSCL2 15832 26580 Lipodystrophy, congenital generalized, type 2; Encephalopathy, progressive, with or without lipodystrophy AR Pediatric Allelic with Neuropathy, distal hereditary motor, type VA (AD); Spastic paraplegia 17, autosomal dominant (AD); Neuronopathy, distal hereditary motor, type VC (AD) Cardiovascular; Endocrine; Neurologic Cardiovascular; Endocrine Dietary measures (eg, restriction of fat intake) and medications (eg, leptin) may be beneficial; Individuals may have cardiomyopathy, and surveillance and early medical management may be beneficial 5964029; 10908191; 14602785; 12362029; 14981520; 15732094; 16427281; 17671040; 19396477; 19041432; 21126715; 20301391; 23142943; 23564749 BSG 1116 682 Blood group, OK BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 9130641 BSND 16512 7809 Bartter syndrome, type 4A; Sensorineural deafness with mild renal dysfunction AR Pediatric Audiologic/Otolaryngologic; Renal Audiologic/Otolaryngologic; Renal Individuals may have renal perturbations, (eg, including metabolic alkalosis and hypokalemia), for which treatment can be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 11687798; 12574213; 19646679; 21158220; 21269598; 23110775; 30174009; 31667618 BTD 1122 686 Biotinidase deficiency AR Pediatric Allergy/Immunology/Infectious; Biochemical; Dermatologic; Neurologic; Ophthalmologic Biochemical Individuals with severe biotinidase deficiency can present with a range of neurologic, visual, and dermatologic anomalies, which are typically not reversible after manifesting, and medical management (with oral biotin) is indicated and can prevent sequelae if instituted early; Raw eggs should be avoided due to resultant decreased biotin bioavailability 4103667; 917614; 88555; 99258; 7436398; 6790844; 6135889; 6137736; 6848914; 3930842; 3926500; 4000223; 4073853; 196050; 2502673; 2515386; 2109151; 1729884; 8283357; 7550325; 9396567; 9375914; 9654207; 15776412; 7550325; 11313766; 17382128; 21752405; 20301497; 21696988; 21907891; 22378278; 22241090 BTG4 13862 54766 Oocyte maturation defect 8 AR N/A N/A Obstetric General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32502391 BTK 1133 695 Isolated growth hormone deficiency, type III with agammaglobulinemia; Agammaglobulinemia, X-linked 1 XL Pediatric Allergy/Immunology/Infectious; Endocrine Allergy/Immunology/Infectious; Endocrine Antiinfectious prophylaxis, including gammaglobulins, sometimes with prophylactic antibiotics and early and aggressive treatment of infections may be beneficial; Live viral vaccines should be avoided; Recognition and treatment of growth hormone deficiency may be beneficial 13380950; 4578158; 3488506; 6783908; 8380905; 8013627; 7722175; 8982147; 9545398; 11445810; 12378199; 12217331; 12958074; 16159644; 16297664; 16377251; 19302039; 19651503; 18241230; 20301626 BUB1B 1149 701 Mosaic variegated aneuploidy syndrome 1; Premature chromatid separation trait AD/AR Pediatric Musculoskeletal; Neurologic; Obstetric; Oncologic; Ophthalmologic Obstetric; Oncologic The condition can involve a number of congenital anomalies Mosaic variegated aneuploidy syndrome is frequently but not always clinically recognizable, and there is a high risk of malignancy, for which surveillance and early treatment may be beneficial; Premature chromatid separation has been described as potentially affecting fertility, and reproductive counseling as well as preconception planning may be beneficial 2935477; 3780318; 8225320; 9677059; 10429359; 9916837; 11169558; 11746029; 15475955; 15098246; 16411201; 21190457 BVES 1152 11149 Muscular dystrophy, limb-girdle, autosomal recessive, 25 AR Pediatric Cardiovascular; Musculoskeletal Cardiovascular Individuals have been described as developing cardiac arrhythmias in early adulthood, and awareness may allow prompt diagnosis, surveillance, and management 26642364 C11ORF80 26197 79703 Hydatidiform mole, recurrent, 4 AR Pediatric Obstetric; Oncologic Obstetric; Oncologic Women are likely to have pregnancies with hydatidiform moles, and awareness may allow reproductive planning and/or surveillance measures, which may allow early detection and treatment 30388401 C12ORF4 1184 57102 Mental retardation, autosomal recessive 66 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25558065; 27311568; 28097321 C12ORF57 29521 113246 Temtamy syndrome AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17632789; 21937992; 23453665; 23453666; 23633300; 24798461 C12ORF65 26784 91574 Combined oxidative phosphorylation deficiency 7; Spastic paraplegia 55, autosomal recessive AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3479531; 20598281; 23188110; 24198383 C14ORF39 19849 317761 Spermatogenic failure 52; Premature ovarian failure 18 AR N/A N/A Genitourinary; Obstetric General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33508233 C19ORF12 25443 83636 Neurodegeneration with brain iron accumulation 4; Spastic paraplegia 43 AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21981780; 22508347; 23269600; 23447832; 23494994; 23521069; 23857908; 26187298; 29295770; 30298423; 31087512 C1QA 1241 712 C1q deficiency AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Renal Allergy/Immunology/Infectious Individuals are also prone to autoimmune disease (eg, glomerulonephritis, SLE) While the majority of sequelae may involve autoimmune manifestations (for which treatment with FFP may be beneficial), some individuals have been described with frequent and/or severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 6445507; 6319055; 7594474; 8840296; 9225968; 10776791; 20560256; 22576477 C1QB 1242 713 C1q deficiency AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Renal Allergy/Immunology/Infectious Individuals are also prone to glomerulonephritis and SLE While the majority of sequelae may involve autoimmune manifestations (for which treatment with FFP may be beneficial), some individuals have been described with frequent and/or severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 6445507; 6319055; 2894352; 23651859 C1QBP 1243 708 Combined oxidative phosphorylation deficiency 33 AR Pediatric Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Renal Cardiovascular Among other features, individuals have been described as manifesting with cardiomyopahty, and awareness may allow early diagnosis and management 28942965 C1QC 1245 714 C1q deficiency AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Renal Allergy/Immunology/Infectious Individuals are also prone to glomerulonephritis and SLE While the majority of sequelae may involve autoimmune manifestations (for which treatment with FFP may be beneficial), some individuals have been described with frequent and/or severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 6445507; 6319055; 8630118; 225968 C1QTNF5 14344 114902 Late-onset retinal degeneration AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12944416; 22277927; 23289492 C1R 1246 715 Ehlers-Danlos syndrome, periodontal type 1 AD Pediatric Allergy/Immunology/Infectious; Cardiovascular; Dental; Dermatologic; Gastrointestinal; Musculoskeletal Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal The condition has been described as inolving risk of arterial and gastrointestinal rupture, and awareness may allow prompt diagnosis and management; Individuals have been described as being prone to recurrent infections, and awareness may allow prompt diagnosis and management 27745832 C1S 1247 716 Ehlers-Danlos syndrome, periodontal type 2; Complement component C1s deficiency AD/AR Pediatric Allergy/Immunology/Infectious; Dental; Dermatologic; Musculoskeletal; Oncologic; Renal Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Oncologic Ehlers-Danlos syndrome, periodontal type has been described as inolving risk of arterial and gastrointestinal rupture as well as recurrent infections, and awareness may allow prompt diagnosis and management; Individuals with Ehlers-Danlos syndrome, periodontal have been described with Wilms tumor (as well as other types of neoplasms), and awareness may allow early detection and treatment; Individuals with Complement component C1s deficiency may suffer from conditions such as severe infections, for which prophylaxis and/or early and aggressive treatment of infection may be beneficial; Immunosuppression may be beneficial for autoimmune phenomena (such as lupus nephritis) 9856483; 9973493; 11390518; 19155518; 20191570; 27745832 C2 1248 717 Complement component 2 deficiency AR Pediatric Allergy/Immunology/Infectious; Renal Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial for infectious manifestations; Patients may also develop autoimmune manifestations, and treatment with immune modulators has been described 14446782; 4161820; 1124106; 2582254; 1542325; 1361318; 1577763; 8621452; 15643297; 16026838; 20417301; 20890976; 22842196 C2CD3 24564 26005 Orofaciodigital syndrome XIV AR N/A N/A Cardiovascular; Craniofacial; Dental; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24997988 C3 1318 718 Complement component 3 deficiency, autosomal recessive; Hemolytic uremic syndrome, atypical, susceptibility to, 5 AD/AR Pediatric Allelic with Macular degeneration, age-related (AD) Allergy/Immunology/Infectious; Dermatologic; Hematologic; Ophthalmologic;Renal Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic; Renal In Complement component 3 deficiency, individuals may manifest with frequent infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals may develop renal disease, and awareness may allow early management of renal sequelaentiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; In hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications) 4117597; 1976733; 1350678; 1575793; 15781264; 18796626; 19846853; 20807612; 20595690; 22410797 C4A 1323 720 Blood group, Chido/Rodgers system BG Pediatric Allelic with Complement component 4A deficiency (AR) Allergy/Immunology/Infectious; Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 4190973; 6932037; 7451653; 2862466; 3260957; 2551816; 2295875; 2243578; 2289315; 2384609; 8473511; 7706484; 22387014; 29928053 C4B 1324 721 Complement component 4B deficiency AR N/A N/A Allergy/Immunology/Infectious General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4190973; 7451653; 2862466; 3501712; 3260957; 3265961; 2551816; 2384609; 1401055; 20580617; 22387014; 29928053 C5 1331 727 Eculizumab, poor response to; Complement component 5 deficiency AD/AR Pediatric Craniofacial; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Pharmacogenomic In Complement component 5 deficiency, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Heterozygous variants have been described as resulting in poor response to eculizumab 5411128; 4258194; 7730648; 21270745; 21635555; 22123893; 22668955; 23371790 C6 1339 729 Complement component 6 deficiency AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial Antiinfectious prophylaxis (including related to specific immunization) and early and aggressive treatment of infections may be beneficial 11344568; 11344569; 6835295; 8690922; 17257682; 17893986; 21270745; 22123893; 22288589; 22668955 C7 1346 730 Complement component 7 deficiency AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial 3685247; 2792129; 8892662; 8871666; 17407100; 15328683; 21270745; 22123893; 20591074; 22206826 C8A 1352 731 Complement component 8 deficiency, type I AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial 6822660; 6433145; 9759902; 21270745; 22123893 C8B 1353 732 Complement component 8 deficiency, type II AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial 6822660; 8098723; 9476133; 21270745; 22123893 C8ORF37 27232 157657 Bardet-Biedl syndrome 21; Cone-rod dystrophy 16; Retinitis pigmentosa 64 AR N/A N/A Dental; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22177090; 26854863; 27008867 C9 1358 735 Complement component 9 deficiency AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious In some individuals, there has been no evidence of "predicted" sequelae (eg, Neisseria infections) Antiinfectious prophylaxis (including related to specific immunization) and early and aggressive treatment of infections may be beneficial 7430628; 2744767; 8747118; 9703418; 10083734; 12596049; 15943177; 21270745; 22123893; 22381107 C9ORF72 28337 203228 Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21944778; 21944779; 23551834; 23597494; 24027057 CA12 1371 771 Hyperchlorhidrosis, isolated AR Pediatric Renal Renal In infancy, salt wasting can lead to severe hyponatremic dehydration/hyperkalemia, and precautionary measures (eg, sodium supplementation) can be beneficial 21035102; 21184099 CA2 1373 760 Osteopetrosis, autosomal recessive 3 AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic; Renal Musculoskeletal; Renal Identification and treatment of renal tubular acidosis may be beneficial; Awareness of multi-organ system complications of osteopetrosis may allow surveillance and prompt management 5041390; 7386510; 7312081; 3925334; 3081869; 2107079; 1928091; 1301935; 1542674; 8127074; 7627193; 8834238; 9143915; 12566520 CA4 1375 762 Retinitis pigmentosa 17 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7581389; 9385361; 15090652; 15563508; 17652713 CA5A 1377 763 Carbonic anhydrase VA deficiency AR Pediatric Biochemical Biochemical Medical treatment (eg, with N-carbamyl-L-glutamate (NCG) alone or with other treatments) has been reported as resolving hyperammonemia in affected individuals 24530203; 26913920 CA8 1382 767 Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19461874; 21937992 CABP2 1385 51475 Deafness, autosomal recessive 93 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 22981119; 21542834 CABP4 1386 57010 Cone-rod synaptic disorder, congenital nonprogressive AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16960802; 23714322 CACNA1A 1388 773 Episodic ataxia, type 2; Migraine, familial hemiplegic 1; Spinocerebellar ataxia 6 AD Pediatric Allelic with Spinocerebellar ataxia 6 (AD); Developmental and epileptic encephalopathy 42 (AD) Neurologic Neurologic; Pharmacogenomic Medical treatment (eg, 4-aminopyridine, acetazolamide, as well as other standard migraine-related medications to treat migraines) may be effective; In Migraine, familial hemiplegic 1, vasoconstricting agents (due to risk of stroke) and cerebral angiography (due to risk of precipitation of attack) should be avoided; In Spinocerebellar ataxia 6, ataxia may be managed medically (with acetazolamide); Vestibular symptoms may be managed medically (eg, with diphenhydramine, baclofen, and gabapentin. 4-aminopyridine) 6684259; 3469025; 1575453; 7757080; 8898206; 14681882; 9311738; 9302278; 9259274; 9259275; 8734765 ; 9403486; 9345107; 8988170; 15210532; 9915947; 10668728; 11439943; 11673601; 12081723; 12056940; 12707077; 14681882; 14718690; 15136697; 15362569; 16186543; 15710862; 15747371; 17575281; 17142831; 18541804; 18685131; 20301319; 20301562; 19633872; 21734179; 20837964; 23934111; 27476654; 28856914; 31824404 CACNA1B 1389 774 Dystonia 23 AD Pediatric Allelic with Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements (AR) Cardiovascular; Neurologic Cardiovascular As the condition can include cardiac arrhythmias, awareness may allow surveillance and early management 21370267; 25296916; 30982612 CACNA1C 1390 775 Brugada syndrome 3; Timothy syndrome; Long QT syndrome 8 AD Pediatric Allergy/Immunology/Infectious; Cardiovascular; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Cardiovascular; Pharmacogenomic In Timothy syndrome, features may be clinically recognizable, but individuals may be at risk for lethal arrhythmias; Somatic mosaicism has been described in Timothy syndrome For Brugada syndrome-related manifestations, surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever; For immune deficiency (such as is described in some individuals with Timothy syndrome), preventive measures and monitoring and early and aggressive treatment of infections may be beneficial; Individuals with long QT syndrome may present with severe cardiac manifestations, including arrhythmias, syncope, and sudden death, and surveillance, preventive measures (eg, including avoidance of dangerous or excacerbating factors), and treatment (eg, including medical treatment with beta-blockers or ICD placement, which have both been described as beneficial in affected individuals) may allow early and beneficial management 1318983; 7572644; 15454078; 15863612; 17224476; 21910241; 20301690; 23677916; 25633834; 30345660 CACNA1D 1391 776 Primary aldosteronism, seizures, and neurologic abnormalities; Sinoatrial node dysfunction and deafness AD/AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Neurologic Audiologic/Otolaryngologic; Cardiovascular; Endocrine In Primary aldosteronism, seizures, and neurologic abnormalities, individuals may manifest with arrhythmias and other cardiac abnormalities, and awareness may allow prompt detection and treatment; Individuals may manifest with endocrine anomalies (eg, hypokalemia, hypoglycemia, hyperaldostorenemia), and awareness may allow early diagnosis and treatement, which has been described as benefitting some parameters; In Sinoatrial node dysfunction and deafness, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals may demonstrate evidence of dysrhythmias (eg, manifesting with bradycardia, with syncopal episodes associated with and without physical activity and stress described), and surveillance (eg, with EKG) may be beneficial in order to allow early medical management 21131953; 23913001 CACNA1E 1392 777 Developmental and epileptic encephalopathy 69 AD Pediatric Neurologic Neurologic The condition can result in severe seizures, and some individuals have been described as responding favorably to medical management with topiramate 30343943 CACNA1F 1393 778 Aland Island eye disease; Cone-rod dystrophy, X-linked, 3; Night blindness, congenital stationary, X-linked, type 2A XL N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14230113; 14213931; 9662400; 9662399; 11381068; 12111638; 12807962; 16505158; 17525176; 20001510; 20301423; 22194652; 22744390 CACNA1G 1394 8913 Spinocerebellar ataxia 42; Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26456284; 26715324; 29878067 CACNA1H 1395 8912 Hyperaldosteronism, familial, type IV AD Pediatric Allelic with Epilepsy, childhood absence, susceptibility to, 6 (AD) Endocrine; Neurologic Endocrine Individuals may have severe hypertension, and awareness may allow medical (and possibly surgical, with adrenalectomy) treatment 12891677; 15048902; 17696120; 25907736 CACNA1S 1397 779 Malignant hyperthermia, susceptibility to, 5; Thyrotoxic period paralysis, susceptibility 1; Hypokalemic periodic paralysis, type 1 AD Pediatric Cardiovascular; Endocrine; Musculoskeletal; Renal Cardiovascular; Endocrine; Pharmacogenomic; Renal In Malignant hyperthermia, early diagnosis, discontinuation of potent inhalation agents/succinylcholine, treatment of metabolic abnormalities, and administration of dantrolene sodium intravenously are essential to treat acute MH; In Thyrotoxic periodic paralysis, treatment of hyperthyroidism results in resolution of paralysis; In Hypokalemic periodic paralysis, paralytic crises can be treated with potassium; Dietary (eg, low sodium/carbohydrate) and medical (eg, potassium, acetazolamide) therapy can be effective; Cardiac surveillance can be beneficial 1148686; 457125; 3855357; 3839536; 8004673; 7897626; 9199552; 11591859; 11353725; 15001631; 15534250; 18835861; 19118277; 20301512; 20301325; 22253645; 22094484; 22901280 CACNA2D2 1400 9254 Cerebellar atrophy with seizures and variable developmental delay AR N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23339110; 29997391 CACNA2D4 20202 93589 Retinal cone dystrophy 4 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17033974 CACNB2 1402 783 Brugada syndrome 4 AD Pediatric Cardiovascular Cardiovascular; Pharmacogenomic Surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever 17224476; 20301690; 22090166 CACNB4 1404 785 Episodic ataxia, type 5 AD Pediatric Allelic with Epilepsy, idiopathic generalized, susceptibility to, 9 (AD), which appears to be an incompletely penetrant condition, and for which optimal seizure control would be beneficial, but may not otherwise require specific interventions Neurologic Neurologic Variants may modify seizure-related conditions due to variants in other genes (eg, SCN1A) Individuals may manifest with recurrent attacks of vertigo and ataxia, and treatment with acetazolamide has been reported as being effective 10762541; 16100538; 18755274; 20301317 CACNG2 1406 10369 Mental retardation, autosomal dominant 10 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21376300 CAD 1424 790 Developmental and epileptic encephalopathy 50 AR Pediatric Biochemical; Gastrointestinal; Hematologic; Neurologic; Renal Biochemical; Gastrointestinal; Renal Medical management (with uridine) has been described as beneficial; Among other manifestations, the conditions has been described as including renal tubular acidosis, which has been reported as amenable to treatment (eg, with citrate); The condition has been reported as including pan-disaccharidase deficiency, which was treated (with probiotics and digestive enzymes) 25678555; 28007989 CALCRL 16709 10203 Lymphatic malformation 8 AR N/A N/A Cardiovascular General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30115739 CALM1 1442 801 Long QT syndrome 14; Ventricular tachycardia, catecholaminergic polymorphic, 4 AD Pediatric Cardiovascular; Neurologic Cardiovascular Individuals may present with severe cardiac manifestations, including arrhythmias, syncope, and sudden death, and surveillance, preventive measures (eg, including avoidance of dangerous or excacerbating factors), and treatment (eg, including medical treatment with beta-blockers or ICD placement, which have both been described as beneficial in affected individuals) may allow early and beneficial management 23040497; 23388215; 24076290 CALM2 1445 805 Long QT syndrome 15 AD Pediatric Cardiovascular; Neurologic Cardiovascular Individuals may suffer from early-onset severe and potentially lethal arrhythmias, and awareness may allow preventive treatment (eg, with beta-blocking medications and ICD placement) and rapid medical response, which may potentially ameliorate morbidity and mortality 23388215; 24917665 CALM3 1449 808 Long QT syndrome 16 AD N/A N/A Cardiovascular Cardiovascular Individuals may present with severe cardiac manifestations, including arrhythmias, syncope, and sudden death, and surveillance, preventive measures (eg, including avoidance of dangerous or excacerbating factors), and treatment (eg, including medical treatment or ICD placement, which have both been described as beneficial in affected individuals) may allow early and beneficial management 25460178; 27516456; 31454269 CALR3 20407 125972 Cardiomyopathy, familial hypertrophic, 19 AD Pediatric Cardiovascular Cardiovascular Surveillance (eg, including echocardiography) for manifestations can allow early diagnosis, preventive measures relating to disease sequelae, and prompt treatment, which may reduce morbidity and mortality 16199542; 17655857 CAMK2A 1460 815 Mental retardation, autosomal dominant, 53; Mental retardation, autosomal recessive, 63 AD/AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28130356; 29100089; 29784083 CAMK2B 1461 816 Mental retardation, autosomal dominant, 54 AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28130356; 29100089 CAMK2G 1463 818 Intellectual developmental disorder, autosomal dominant 59 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23033978; 30184290 CAMTA1 18806 23261 Cerebellar ataxia, nonprogressive, with mental retardation AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22693284 CANT1 19721 124583 Desbuquois dysplasia 1 AR Pediatric Allelic with Epiphyseal dysplasia, multiple, 7 (AR) Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic Ophthalmologic As the condition can include glaucoma, appropriate surveillance may allow early detection and management 1080993; 1959544; 7977470; 14679586; 14679587; 15211652; 19853239; 20358610; 20425819; 20358597; 21037275; 21412251; 21654728; 22539336 CAPN1 1476 823 Spastic paraplegia 76, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27153400 CAPN15 11182 6650 Oculogastrointestinal neurodevelopmental syndrome AR N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32885237; 33410501 CAPN3 1480 825 Muscular dystrophy, limb-girdle, autosomal dominant 4; Muscular dystrophy, limb-girdle, autosomal recessive, 1 AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7720071; 10069710; 10330340; 15694138; 16607617; 16971480; 18854869; 21204801; 22378277; 22622166; 22926650; 27259757; 28881388 CAPN5 1482 726 Vitreoretinopathy, neovascular inflammatory AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23055945 CARD11 16393 84433 B-cell expansion with NFKB and T-cell anergy; Immunodeficiency 11B with atopic dermatitis; Immunodeficiency 11A AD/AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Oncologic Allergy/Immunology/Infectious; Oncologic For Immunodeficiency 11A and 11B and B-cell expansion with NFKB and T-cell anergy, individuals may be prone to frequent infections, and prophylactic measures, as well as early and aggressive treatment of infections may be beneficial; For B-cell expansion with NFKB and T-cell anergy, individuals may be predisposed to B cell malignancy, and awareness may allow early recognition and management; HSCT has been described in Congenital B cell lymphocytosis 23129749; 23374270; 23561803; 25352053; 25930198 CARD14 16446 79092 Pityriasis rubra pilaris; Psoriasis 2 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8178173; 15689454; 22521418 CARD8 17057 22900 Inflammatory bowel disease 30 AD Pediatric Allergy/Immunology/Infectious; Gastrointestinal Allergy/Immunology/Infectious; Gastrointestinal The condition can involve sequelae of inflammatory bowel disease, and medical management (eg, with steroids, anti-IL1B monoclonal antibodies) have been described as beneficial 29408806 CARD9 16391 64170 Candidiasis, familial, 2 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals can have recurrent (and lethal) fungal infections, and surveillance, prophylaxis, and early treatment may be beneficial 19864672; 22703878; 23335372; 24131138 CARMIL2 27089 146206 Immunodeficiency 58 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Oncologic; Pulmonary Allergy/Immunology/Infectious; Oncologic Individuals may have severe and frequent infections, and prophylactic measures, as well as early and aggressive treatment of infections may be beneficial; Individuals may be at increased risk of certain types of neoplasms, and awareness may allow prompt diagnosis and management 27647349; 27896283; 28112205; 29479355 CARS1 1493 833 Microcephaly, developmental delay, and brittle hair syndrome AR N/A N/A Dermatologic; Endocrine; Gastrointestinal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30824121 CARS2 25695 79587 Combined oxidative phosphorylation deficiency 27 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25361775; 25787132 CASK 1497 8573 Mental retardation and microcephaly with pontine and cerebellar hypoplasia; FG syndrome 4; Mental retardation, with or without nystagmus XL Pediatric Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12522552; 19165920; 19200522; 19377476; 20029458; 21735175; 21954287 CASP10 1500 843 Autoimmune lymphoproliferative syndrome, type IIA AD Pediatric Allergy/Immunology/Infectious; Hematologic; Oncologic Allergy/Immunology/Infectious; Oncologic Variants may modify other related disorders Lymphoproliferation can be suppressed with medications such as corticosteroids, cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil; BMT/HSCT the only curative treatment for ALPS, has to date mostly been reported in patients with severe clinical findings; Surveillance for manifestations of lymphoproliferation and autoimmunity, and specialized imaging studies to detect malignant transformation may be beneficial 10412980; 16537120; 16446975; 17999750; 20301287 CASP14 1502 23581 Ichthyosis, congenital, autosomal recessive 12 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27494380 CASP8 1509 841 Caspase 8 defiency AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 12353035; 15459299; 19930184; 21447005 CASQ1 1512 844 Myopathy, vacuolar, with CASQ1 aggregates AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25116801 CASQ2 1513 845 Ventricular tachycardia, catecholaminergic, polymorphic, 2 AR Pediatric Cardiovascular Cardiovascular Individuals may present with sudden cardiac death (eg, in the setting of exercise or excited states), and the overall mortality in untreated individuals is high early in life, such that surveillance and preventive measures/medical management, including ICD treatment, may be helpful to help decrease morbidity (however, storms of ventricular tachycardia have been described as being treated but not terminated through ICD shocks, and did not degenerate to ventricular fibrillation) 11401939; 16908766; 22481011; 22650415 CASR 1514 846 Hyperparathyroidism, neonatal; Hypocalcemia, autosomal dominant 1; Hypocalciuric hypercalcemia, type I; Hyperparathyroidism, neonatal severe primary; Hypoparathyroidism, familial isolated; Hyperparathyroidism, familial primary AD/AR Pediatric Allelic with Idiopathic generalized epilepsy 8 (AD) Endocrine; Musculoskeletal; Neurologic; Renal Endocrine; Renal Sequelae, which can be severe in some individuals with hyperparathyrodism, can include seizures, and treatment (eg, with Vitamin D and calcium) can be effective at preventing morbidity; Early diagnosis of NSPHT is critical as the disorder can neurologically devastating or lethal without parathyroidectomy; In some forms of hypoparathyroidism, treatment of hypocalcemia with vitamin D/ vitamin D metabolites can cause hypercalciuria and resultant renal impairment, and PTH injections or diuretic treatment may be effective; In familial hypocalciuric hypercalcemia, accurate diagnosis may be important in order to decrease the use of unhelpful therapies 18887540; 14089114; 5013415; 830920; 619857; 7054696; 3966479; 7916660; 7874174; 7673400; 7726161; 8132750; 8675635; 8733126; 8813042; 9109436; 9011580; 9253358; 9642634; 9661634; 11013439; 10770217; 11134112; 11701698; 11293637; 12107202; 12241879; 12915654; 15579740; 15241791; 16608894; 17698911; 17018660; 18328986; 18756473; 21986511; 19250271; 22315359 CAST 1515 831 Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads (PLACK) AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25683118 CAT 1516 847 Acatalasemia AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious; Pharmacogenomic Individuals may be prone to manifestations such as oral ulcers and gangrene, and prompt treatment of infections may be beneficial; Pharmacogenomically, variants may be related to adverse reactions with treatment with medications such as uric acid oxidase 12991731; 13904105; 2308162; 1999334; 1591863; 1551654; 8673475; 11117918; 11001624; 11197178; 11603354; 11500062; 15771551; 15800961; 17729111 CATSPER1 17116 117144 Spermatogenic failure 7 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19344877 CAV1 1527 857 Pulmonary hypertension, primary 3; Lipodystrophy, familial partial, type 7; Lipodystrophy, congenital generalized, type 3 AD/AR Pediatric Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary Cardiovascular; Endocrine; Gastrointestinal; Pulmonary Individuals with Pulmonary hypertension, primary, may manifest at variable ages, and awareness may allow surveillance, diagnosis of sequelae, and prompt management of disease; In Lipodystrophy, congenital generalized and Lipodystrophy, familial partial, dietary measures and medications may be beneficial; Surveillance for manifestations, including diabetes and abnormal lipid balance may allow early diagnosis and treatment 15028826; 18211975; 18237401; 21865368; 22474227 CAV3 1529 859 Cardiomyopathy, familial hypertrophic; Long QT syndrome 9; Creatine phosphokinase, elevated serum AD/Digenic Pediatric Allelic with Muscular dystrophy, limb-girdle, type IC (AD); Myopathy, distal, Tateyama type (AD); Rippling muscle disease 2 (AD/AR) Cardiovascular; Musculoskeletal Cardiovascular; Pharmacogenomic Conditions may involve digenic inheritance Preventive measures and medical management may be helpful to help decrease morbidity related to cardiovascular manifestations; In individuals with isolated CK elevation, precautions should be taken during surgical/anesthetic procedures and anesthesia due to malignant hyperthermia risk 2705900; 9536092; 9537420; 10220144; 10227634; 10746614; 11431690; 11251997; 11805270; 12939441; 12666119; 14672715; 15668980; 16247063; 17060380; 17275750; 20229577; 20301308; 20301559; 20809527; 22245016; 22581547 CAVIN1 9688 284119 Lipodystrophy, congenital generalized, type 4 AR N/A N/A Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal Cardiovascular Among other manifestations, individuals may demonstrate cardiac arrhythmias, and appropriate surveillance and management may be beneficial 12116229; 18698612; 19726876; 20300641; 20684003 CBL 1541 867 Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia; Juvenile myelomonocytic leukemia, familial AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic Cardiovascular; Oncologic For Noonan syndrome, surveillance to allow early diagnosis and treatment of malignancy may reduce morbidity; The condition may also include cardiac anomalies and dysrhythmias, and appropriate surveillance and care may be beneficial; For Juvenile myelomonocytic leukemia, awareness may allow early detection and treatment of disease 20694012; 20543203; 25358541; 25939664 CBLIF 4268 2694 Intrinsic factor deficiency AR Pediatric Gastrointestinal; Hematologic Gastrointestinal Digenic disease (with FUT2 variants) has been described Individuals typically present in infancy (though presentations at much later ages have been reported) with pernicious (megaloblastic) anemia, and vitamin B12 administration can be effective 2071148; 14695536; 14576042; 15738392; 20408840; 22929189; 23402911; 23430489 CBS 1550 875 Homocystinuria due to cystathionine beta-synthase deficiency AR Pediatric Biochemical; Cardiovascular; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Biochemical; Hematologic; Ophthalmologic; Pharmacogenomic Some individuals may respond to medical therapy (eg, pyridoxine, folic acid, betaine, hydroxycobalamin) and/or dietary therapy (eg, methionine restriction); Surveillance for and prompt treatment of thromboembolic complications can be beneficial; Awareness of ocular complications (eg, ectopia lentis) can allow prompt and appropriate treatment; Certain agents (eg, oral contraceptives) should be avoided, and special considerations may need to be taken into account if surgery is required 14018926; 13960563; 5658872; 5658866; 7325153; 6711564; 4033699; 934499; 3591841; 2116556; 7506602; 7967489; 7762555; 8554066; 8592550; 8940271; 9427154; 9787359; 10364517; 10338090; 10564686; 10780316; 11343305; 11596648; 12124992; 12227460; 12007221; 12118525; 11857551; 12552044; 14635102; 16205833; 17686644; 20142522; 20301697; 18280597; 19370759; 19819175; 21520339; 21308989; 21240075; 20567906; 21626167; 24168815; 24169224 CBX2 1552 84733 46,XY sex reversal 5 AR N/A N/A Endocrine; Genitourinary General There was no evidence for dysgenetic gonads in the reported patient; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19361780 CC2D1A 30237 54862 Mental retardation, autosomal recessive 3 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16033914; 17149387 CC2D2A 29253 57545 COACH syndrome 2 AR Pediatric Allelic with Joubert syndrome 9 (AR); Meckel syndrome 6 (AR) Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal Gastrointestinal The condition can involve multiple congenital anomalies; Digenic inheritance has been reported In COACH syndrome, among other findings, individuals may have hepatic disease, and it has been suggested that identification of liver disease is critical as some patients may develop complications such as portal hypertension with fatal variceal bleeding 18950740; 18387594; 18513680; 20301500; 20671153; 22246503; 22241855 CCBE1 29426 147372 Hennekam lymphangiectasia-lymphedema syndrome AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Neurologic; Renal Allergy/Immunology/Infectious; Endocrine; Gastrointestinal The condition can include manifestations such as protein-losing enteropathy (which may be refractory), as well as features for which treatment can be beneficial, such as infectious sequelae, for which early and aggressive treatment may be beneficial; Individuals have been described with endocrine manifestations such as hypothyroidism and growth hormone deficiency, and awareness may allow prompt recognition and treatment 2624276; 1897580; 8465855; 7645602; 10925377; 12124738; 12376947; 14564208; 12794699; 19935664; 19911200; 22239599 CCDC103 32700 388389 Ciliary dyskinesia, primary, 17 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 19720631; 20301301; 22581229 CCDC115 28178 84317 Congenital disorder of glycosylation, type IIo AR Pediatric Biochemical; Craniofacial; Gastrointestinal; Hematologic; Neurologic Hematologic Liver transplant has been described Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 26833332 CCDC137 33451 339230 Schizophrenia AD N/A N/A Neurologic General Evidence or clinical applicability unclear 21743468 CCDC174 28033 51244 Hypotonia, infantile, with psychomotor retardation AR N/A N/A Cardiovascular; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26358778 CCDC22 28909 28952 Ritscher-Schinzel syndrome 2 XL N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic General The condition can involve multiple anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21826058; 24916641 CCDC28B 28163 79140 Bardet-Biedl syndrome, modifier of AD N/A N/A General General Variants are described as related to modifying alleles, with little evidence that the variant would cause disease alone 12677556; 16327777; 22773737 CCDC32 28295 90416 Cardiofacioneurodevelopmental syndrome AR Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic Cardiovascular Individuals have been described with congenital heart anomalies, including valvulvar defects, and awareness may allow early diagnosis and management of these issues 32307552 CCDC39 25244 339829 Ciliary dyskinesia, primary, 14 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 20301301; 21131972 CCDC40 26090 55036 Ciliary dyskinesia, primary, 15 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 20301301; 21131974 CCDC47 24856 57003 Trichohepatoneurodevelopmental syndrome AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Dental; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Among other findings, individuals have been described with susceptibility to infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 30401460 CCDC50 18111 152137 Deafness, autosomal dominant 44 AD N/A N/A Audiologic/Otolaryngologic General Hearing loss has been reported to occur in the first decade (6-10 years) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12483295; 17503326 CCDC65 29937 85478 Ciliary dyskinesia, primary, 27 AR Pediatric Allergy/Immunology/Infectious; Pulmonary Allergy/Immunology/Infectious; Pulmonary Pulmonary surveillance may be beneficial to assess respiratory function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 23991085; 24094744 CCDC78 14153 124093 Myopathy, centronuclear, 4 AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22818856 CCDC8 25367 83987 Three M syndrome 3 AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21737058 CCDC88A 25523 55704 PEHO-like syndrome AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26917597 CCDC88C 19967 440193 Spinocerebellar ataxia 40; Hydrocephalus, congenital, 1 AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21031079; 23042809; 25062847 CCM2 21708 83605 Cerebral cavernous malformations 2 AD Pediatric Cardiovascular; Neurologic Cardiovascular; Neurologic; Pharmacogenomic Surveillance measures (eg, spinal cord MRI, annual brain gradient echo or susceptibility-weighted imaging) has been advocated; Agents that increase risk of hemorrhage should be avoided (eg, aspirin, NSAIDs, heparin, warfarin). 14624391; 17211633; 17160895; 18060436; 18779516; 19088123; 21543988; 20301470 CCN6 12771 8838 Progressive pseudorheumatoid dysplasia AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6807993; 6410512; 6873109; 6431106; 8275575; 9222963; 10471507; 16152649; 19064006; 21528827 CCND2 1583 894 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24705253 CCNF 1591 899 Frontotemporal dementia and/or amyotrophic lateral sclerosis 5 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27080313 CCNK 1596 8812 Intellectual developmental disorder with hypertelorism and distinctive facies AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30122539 CCNO 18576 10309 Ciliary dyskinesia, primary 29 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 24747639; 24824133 CCNQ 28434 92002 Toe syndactyly, telecanthus, and anogenital and renal malformations (STAR syndrome) XL N/A N/A Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8818947; 18297069 CCT5 1618 22948 Neuropathy, hereditary sensory, with spastic paraplegia AR N/A N/A Neurologic General Among other neurologic features, individuals can demonstrate insensitivity to pain, which can result in injuries and infections Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16399879 CD151 1630 977 Raph blood group BG Pediatric Allelic with Nephropathy with pretibial epidermolysis bullosa and deafness (AR) Audiologic/Otolaryngologic; Dermatologic; Hematologic; Renal Hematologic Individuals with Nephropathy with pretibial epidermolysis bullosa and deafness may manifest with deafness, but it is described as typically postlingual Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 3604155; 3238950; 3412548; 15265795; 18522704 CD164 1632 8763 Deafness, autosomal dominant 66 AD Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 26197441 CD19 1633 930 Immunodeficiency, common variable 3 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Indidivuals may demonstrate increased susceptibility to infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 16672701 CD207 17935 50489 Birbeck granule deficiency AD N/A N/A General General The condition may not involve clinical relevance The clinical relevance of the condition is unclear CD247 1677 919 Immunodeficiency due to defect in CD3-Zeta AR Pediatric Allergy/Immunology/Infectious; Gastrointestinal Allergy/Immunology/Infectious Individuals may present with a variety of infectious manifestations, including oral, pulmonary, and skin infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; The use of G-CSF has been reported, as has BMT 3262828; 16672702 CD27 11922 939 Lymphoproliferative syndrome 2 AR Pediatric Allergy/Immunology/Infectious; Hematologic; Oncologic Allergy/Immunology/Infectious; Hematologic; Oncologic HSCT has been described The condition can involve childhood-onset immunodeficiency, and prophylactic measures, treatment, and prompt and aggressive treatment of infections may be beneficial; Individuals may manifest with hemophagocytic lymphohistiocytosis syndrome , and awareness can allow efficient management, but stem cell transplant may be indicated in such instances; Additional malignancies have been described, and awareness may allow recognition and treatment 22197273; 22365582; 22801960 CD2AP 14258 23607 Focal segmental glomerulosclerosis 3 AR Pediatric Renal Renal The condition can involve renal failure, and early diagnosis may enable management considerations; Renal transplant has been described 17713465 CD320 16692 51293 Methylmalonic aciduria, transient, due to transcobalamin receptor defect AR Pediatric Biochemical; Ophthalmologic Biochemical; Ophthalmologic Medical treatment (eg, with IV B6 and IM B12-hydroxocobalamine) has been shown to positively affect laboratory parameters, and may be clinically beneficial though long-term clinical sequelae are unclear 20524213; 22819238 CD36 1663 948 Platelet glycoprotein IV deficiency AR Pediatric Hematologic Hematologic Platelet glycoprotein IV deficiency has been reported with refractoriness to HLA-matched platelet transfusion, and may act as a susceptibility factor for hypertrophic cardiomyopathy and other cardiovascular-related parameters 2617957; 10946357; 11247555; 15973412; 17668374; 17412877 CD3D 1673 915 Immunodeficiency 19 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described with severe combined immunodeficiency, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported 14602880; 15546002 CD3E 1674 916 Immunodeficiency 18 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described with severe combined immunodeficiency, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 8490660; 15546002 CD3G 1675 917 Immunodeficiency 17 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 1709425; 1635567 CD4 1678 920 Immunodeficiency 79 AR Pediatric Allelic with OKT4 epitope deficiency (AD) Allergy/Immunology/Infectious Allergy/Immunology/Infectious The condition may involve early-onset and severe HPV, respiratory, and other infections, and awareness may allow early and agressive treatment of infections, as well as potential preventative measures 6790623; 6209207; 6199335; 6199366; 6229573; 6208600; 1708753; 1961196; 7534484; 7541811; 7689618; 31781092; 33471124 CD40 11919 958 Immunodeficiency with Hyper-IgM, type 3 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported 11675497; 12915844; 12584544; 17502893; 20301576 CD40LG 11935 959 Immunodeficiency, with hyper-IgM, type 1 XL Pediatric Allergy/Immunology/Infectious; Hematologic; Oncologic Allergy/Immunology/Infectious; Oncologic Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals have been described as being at increased risk of malignancy, and awareness may allow early detection and management; BMT has been reported 7679801; 7678782; 7542361; 9255191; 10228294; 10931436; 10655530; 17296845; 20301576; 23010537; 22322937 CD44 1681 960 Blood group, Indian BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 1146277; 8636151 CD46 6953 4179 Hemolytic uremic syndrome, atypical, susceptibility to, 2 AD/AR Pediatric Hematologic; Renal Hematologic; Pharmacogenomic; Renal Digenic inheritance (with CFH) has been reported In hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications), though treatment with plasma infusion was not reported to result in improved disease resolution in individuals with MCP variants 14615110; 14566051; 15661753; 16621965; 16762990; 16386793; 17617869; 16882452; 20595690; 20301541 CD55 2665 1604 Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy; Blood group, Cromer system AR/BG Pediatric Hematologic Hematologic For Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy, individuals may manifest with features denoted by the condition name, with signs and symptoms including abdominal pain/diarrhea, intestinal lymphangiectasia, hypoproteinemic edema, and malabsorption, as well as recurrent infections; with hypogammaglobulinemia, and angiopathic thromboembolism, and medical management (eg, with terminal complement inhibitor eculizumab) has been described as beneficial on laboratory and clinical parameters; The condition can include recurrent infections, and awareness may allow preventative measures and early and aggressive treatment of infections; Blood group, Cromer system, variants associated with a blood group may be important in specific situations (eg, related to transfusion) 7519480; 8837357; 9427725; 21214297; 28657829; 28657861 CD59 1689 966 Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy AR Pediatric Allergy/Immunology/Infectious; Hematologic; Neurologic Allergy/Immunology/Infectious; Hematologic Surveillance to allow early diagnosis and treatment of manifestations including hemolytic anemia, as well as thrombotic risk, may be beneficial; Immunosuppressive treatment has been reported as resulting in clinical improvement 1691667; 1699124; 1382994; 21707954; 23149847 CD70 11937 970 Lymphoproliferative syndrome 3 AR Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic Some individuals may patients may have recurrent infections, and awareness may allow prophylactic measures and prompt and aggressive management of infections; Individuals have been described as having increased susceptibility to Epstein-Barr virus infection, causing increased risk of B-cell malignancies, and awareness may allow prompt diagnosis and management of oncologic disease 28011863; 28011864 CD79A 1698 973 Agammaglobulinemia 3 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 10525050; 11920841 CD79B 1699 974 Agammaglobulinemia 6 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 17675462; 17709424 CD81 1701 975 Immunodeficiency, common variable, 6 AR Pediatric Allergy/Immunology/Infectious; Renal Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 20237408 CD8A 1706 925 CD8 deficiency, familial AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Asymptomatic individuals have been described Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 11435463; 17658607 CD96 16892 10225 C syndrome (Opitz trigonocephaly syndrome) AD N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7258228; 3981579; 2260586; 10405439; 16835930; 16528754; 17847009 CDAN1 1713 146059 Anemia, dyserythropoietic congenital, type Ia AR Pediatric Cardiovascular; Hematologic; Musculoskeletal; Renal Hematologic Individuals may require RBC transfusions in the neonatal period; Medical therapy (eg, with alpha-interferon) may be beneficial; Iron overload is common 718245; 476312; 3096054; 2757972; 2124499; 7725852; 10971401; 10753260; 12434312; 16098079; 16141353; 18824595; 21378561; 21364188; 22504250 CDC14A 1718 8556 Deafness, autosomal recessive 32, with or without immotile sperm AR Pediatric Audiologic/Otolaryngologic; Genitourinary Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 27259055; 29293958 CDC42 1736 998 Takenouchi-Kosaki syndrome AD N/A N/A Cardiovascular; Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26386261; 26708094; 29394990 CDC45 1739 8318 Meier-Gorlin syndrome 7 AR N/A N/A Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27374770 CDC6 1744 990 Meier-Gorlin syndrome 5 AR N/A N/A Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11477602; 21358632; 22333897 CDC73 16783 79577 Hyperparathyroidism 1; Hyperparathyroidism-jaw tumor syndrome; Carcinoma, parathyroid AD Pediatric Endocrine; Oncologic; Renal Endocrine; Oncologic Parathyroidectomy (or medical treatment in individuals unable to undergo parathyroidectomy) may be necessary to normalize calcium levels, and parathyroid adenomas may recur; Surveillance and early diagnosis/treatment of specific manifestations, including jaw tumor recurrence, parathyroid carcinoma, and renal neoplasms, is indicated 11157996; 3592449; 12434154; 14585940; 14715834; 14985403; 15531515; 15606373; 16720667; 17639062; 17666472; 21361849; 20301744; 22187299; 23652676; 23757631 CDCA7 14628 83879 Immunodeficiency-centromeric instability-facial anomalies syndrome 3 AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Gastrointestinal; Neurologic Allergy/Immunology/Infectious Individuals have been described with recurrent childhood infections, and awareness may allow prompt and aggressive treatment of infections 15952214; 1999836; 26216346 CDH1 1748 999 CDH1-related cancer AD Adult Allelic with Blepharocheilodontic syndrome 1 (AD) Craniofacial; Dental; Gastrointestinal; Musculoskeletal; Oncologic Oncologic Variants may also be involved in other malignancies (eg, prostate cancer) either as minor or major risk factors; Variants have also been implicated in the development of facial clefting Surveillance and prophlyactic measures (which may include prophylactic gastrectomy) may allow early diagnosis and treatment (though there is controversy regarding the efficacy of prophlyaxis and surveillance measures), which may potentially be beneficial in the reduction of morbidity and mortality 9751616; 9537325; 10072428; 10477433; 10319582; 11443625; 11968084; 11968083; 12588804; 15235021; 14961571; 16189707; 17660459; 19168852; 20301318; 22020549; 23124477; 23197654; 24037103; 28301459 CDH11 1750 1009 Elsahy-Waters syndrome AR N/A N/A Craniofacial; Dental; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27431290; 28988429; 29271567 CDH15 1754 1013 Mental retardation, autosomal dominant 3 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19012874 CDH2 1759 1000 Arrhythmogenic right ventricular dysplasia 14 AD Pediatric Allelci with Agenesis of corpus callosum, cardiac, ocular, and genital syndrome (AD) Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular The condition may involve cardiac sequelae potentially resulting in sudden cardiac death, and awareness may allow early diagnosis and management (such as with ICD placement) 28280076 CDH23 13733 64072 Pituitary adenoma 5, multiple types; Deafness, autosomal recessive 12; Usher syndrome, type 1D; Usher syndrome, type 1D /F digenic AD/AR/Digenic Pediatric (Deafness, autosomal recessive 12; Usher syndrome, type 1D; Usher syndrome, type 1D /F digenic)/Adult (Pituitary adenoma, multiple types) Audiologic/Otolaryngologic; Oncologic; Ophthalmologic Audiologic/Otolaryngologic; Oncologic Inheritance of Usher syndrome can be digenic, involving PCDH15 For Pituitary adenoma, multiple types, awareness may allow early diagnosis and management of pituitary neoplasms; For Deafness and Usher syndrome, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 11138009; 11090341; 11138008; 15537665; 17850630; 28413019 CDH3 1762 1001 Hypotrichosis, congenital, with juvenile macular dystrophy; Ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome AR N/A N/A Dermatologic; Musculoskeletal; Ophthalmologic General Heterozygotes may display subtle effects Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13372143; 10420194; 11544476; 12445216; 15805154; 20140736; 22140374; 22348569; 23143461 CDHR1 14550 92211 Cone-rod dystrophy 15; Retinitis pigmentosa 65 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20805371 CDIN1 26929 84529 Congenital dyserythropoietic anemia type Ib AR Pediatric Hematologic; Musculoskeletal Hematologic Individuals have been described as manifesting with early childhood onset, severe anemia requiring treatment via RBC transfusion 9220189; 16643456; 16754775; 23716552 CDK10 1770 8558 Al Kaissi syndrome AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28886341 CDK13 1733 8621 Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27479907 CDK19 19338 23097 Developmental and epileptic encephalopathy 87 AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32330417 CDK4 1773 1019 Melanoma, cutaneous malignant, susceptibility to, 3 AD Adult Dermatologic; Oncologic Dermatologic; Oncologic Surveillance for melanoma in at-risk individuals (eg, with regular self-examination and clinical examination) may allow early detection and treatment, which may decrease morbidity and mortality 7652577; 8528263; 9425228; 15880589; 21801156; 23384855; 23546221 CDK5 1774 1020 Lissencephaly 7 with cerebellar hypoplasia AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25560765 CDK5RAP2 18672 55755 Microcephaly, primary autosomal recessive, 3 AR Pediatric Audiologic/Otolaryngologic; Neurologic Audiologic/Otolaryngologic The condition can involve congenital hearing impairment, and early recognition and treatment may improve outcomes, including speech and language development 10677332; 15793586; 17764569; 22887808; 23726037; 23995685 CDK6 1777 1021 Microcephaly 12, primary, autosomal recessive AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23918663 CDK8 1779 1024 Intellectual developmental disorder with hypotonia and behavioral abnormalities AD Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular Individuals have been described as affected with a range of cardiovascular anomalies, including potentially occult anomalies requiring interventions, and awareness may allow early diagnosis and management 30905399 CDKL5 11411 6792 Epileptic encephalopathy, early infantile, 2 XL N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15499549; 15492925; 15689447; 18266744; 18809835; 18063413; 17993579; 19793311; 19241098; 19396824; 20602487; 21765152; 21770923; 21802232; 22264704; 22430159; 22521361; 22670135; 22678952; 22867051; 23064044 CDKN1B 1785 1027 Multiple endocrine neoplasia, type IV AD Pediatric Endocrine; Oncologic Endocrine; Oncologic Surveillance and risk awareness may allow prompt detection and treatment of associated neoplasms (in affected individuals, these have been reported as including primary hyperparathyroidism likely due to underlying neoplasm, pituitary adenoma, and renal angiomyolipoma), which may decrease associated morbidity and mortality 17030811; 20507346; 20824794; 21289244; 22129891; 23555276; 24819502 CDKN1C 1786 1028 IMAGE syndrome; Beckwith-Wiedemann syndrome AD Pediatric Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Renal Endocrine; Oncologic The conditions may involve imprinting mechanisms While IMAGe syndrome may have a number of recognizable features, recognition may allow preventive/treatment measures related to adrenal insufficiency; In Beckwith-Wiedemann syndrome, surveillance and early detection of and treatment for malignancy may decrease morbidity and mortality; Recognition and surveillance for and treatment of neonatal hypoglycemia can be beneficial 8841187; 10424811; 11181570; 11751681; 12439823; 15769992; 15999116; 15887271; 16835919; 18668518; 19302842; 20503313; 20301568; 22585446; 22634751; 24065356 CDKN2A 1787 1029 Melanoma and neural system tumor syndrome; Melanoma, familial; Melanoma-pancreatic cancer syndrome AD Pediatric Dermatologic; Oncologic Dermatologic; Oncologic Other tumor types have been reported Surveillance and diagnosis of malignancies (potentially including, depending on the type of specific condition, melanoma and pancreatic cancer) may allow early diagnosis and treatment, potentially improving outcomes 7987387; 8153634; 7987388; 7666917; 7666916; 8653684; 9328469; 9699728; 9516223; 9603434; 9425228; 9916806; 10874641; 10956390; 1579459; 11506491; 11726555; 12019208; 11815963; 11807902; 12556369; 12700603; 15577313; 16822996; 17492760; 18178632; 20132244; 20653773; 21895773; 21325014; 21150883; 21801156; 20574843; 21570156; 21570154; 21625824; 22368299; 21614589; 22636603 CDON 17104 50937 Holoprosencephaly 11 AD N/A N/A Craniofacial; Endocrine; Neurologic; Ophthalmologic General Individuals with holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21802063 CDSN 1802 1041 Hypotrichosis 2; Peeling skin syndrome 1 AD/AR N/A N/A Allergy/Immunology/Infectious; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3652491; 10793007; 12754508; 20691404; 21191406; 21777220; 22146835 CDT1 24576 81620 Meier-Gorlin syndrome 4 AR N/A N/A Craniofacial; Endocrine; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11477602; 11992493; 21358631 CEACAM16 31948 388551 Deafness, autosomal dominant 4B; Deafness, autosomal recessive 113 AD/AR N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7655461; 21368133; 29703829 CEBPA 1833 1050 Acute myeloid leukemia, familial AD Pediatric Oncologic Oncologic Surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of malignancy, which may reduce morbidity and mortality 15575056; 15902292; 18768433; 18946494; 20963938; 22066712; 23716546 CEBPE 1836 1053 Specific granule deficiency 1 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have severe immunocompromise, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 10359588; 11313242 CEL 1848 1056 Maturity-onset diabetes of the young, type 8, with exocrine dysfunction AD Pediatric Endocrine; Gastrointestinal Endocrine; Gastrointestinal In addition to endocrine manifestations (diabetes mellitus), recognition and specific treatment for exocrine dysfunction may be beneficial 16369531; 18544793; 17989309; 19760265; 21784842; 21521318 CELA2A 24609 63036 Abdominal obesity-metabolic syndrome 4 AD Pediatric Cardiovascular; Endocrine Cardiovascular Among other features, individuals have been described with relatively early-onset cardiac disease, including myocardial infarction, and awareness may allow early interventions to ameliorate cardiovascular and related sequelae 31358993 CELSR1 1850 9620 Lymphatic malformation 9 AD N/A N/A Cardiovascular General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26855770; 31215153; 31403174 CENPE 1856 1062 Microcephaly 13, primary, autosomal recessive AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24748105 CENPF 1857 1063 Stromme syndrome AR N/A N/A Craniofacial; Gastrointestinal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25564561; 26820108 CENPJ 17272 55835 Seckel syndrome 4; Microcephaly, primary autosomal recessive, 6 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12843329; 15793586; 16900296; 20522431; 20978018; 21668957; 22775483 CENPT 25787 80152 Short stature and microcephaly with genital anomalies AR N/A N/A Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29228025 CEP112 28514 201134 Spermatogenic failure 44 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31654588 CEP120 26690 153241 Joubert syndrome 31; Short-rib thoracic dysplasia 13 with or without polydactyly AR N/A N/A Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25361962; 27208211 CEP135 29086 9662 Microcephaly 8, primary, autosomal recessive AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22521416 CEP152 29298 22995 Seckel syndrome 5; Microcephaly 9, primary, autosomal recessive AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20598275; 21131973 CEP164 29182 22897 Nephronophthisis 15 AR N/A N/A Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22863007 CEP19 28209 84984 Morbid obesity and spermatogenic failure AR N/A N/A Endocrine; Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24268657 CEP250 1859 11190 Cone-rod dystrophy and hearing loss 2 AR Pediatric Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic The condition can involve early-onset hearing impairment, and early recognition and treatment may improve outcomes, including speech and language development 24780881; 28005958; 29718797; 30459346 CEP290 29021 80184 Leber congenital amaurosis 10; Meckel syndrome 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal General The condition frequently involves multiple congenital anomalies and multisystemic manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16909394; 16682973; 16682970; 17564974; 17564967; 17554762; 17617513; 17898177; 17705300; 18327255; 20301537; 20690115; 20805370 CEP41 12370 95681 Joubert syndrome 15 AR/Digenic N/A N/A Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary; Renal General The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Digenic inheritance has been reported Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20301500; 22246503 CEP55 1161 55165 Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly (MARCH) AR N/A N/A Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28264986; 28295209 CEP57 30794 9702 Mosaic variegated aneuploidy syndrome 2 AR Pediatric Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary Endocrine The condition can involve multiple congenital anomalies Individuals have been described as manifesting with hypothyroidism (among other features), and medical replacement therapy may be beneficial 12116237; 18548531; 21552266; 24259107 CEP63 25815 80254 Seckel syndrome 6 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21983783 CEP78 25740 84131 Cone rod dystrophy and hearing loss 1 AR Pediatric Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic The condition can involve early-onset hearing impairment, and early recognition and treatment may improve outcomes, including speech and language development 27588451; 27588452; 27627988 CEP83 17966 51134 Nephronophthisis 18 AR N/A N/A Gastrointestinal; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24882706 CEP85L 21638 387119 Lissencephaly 10 AD N/A N/A Neurologic; Ophthalmologic General As with other genetic conditions that can involve seizures, knowledge of the genetic cause may be helpful for medication selection based on what has been beneficial in other patients Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32097630 CERKL 21699 375298 Retinitis pigmentosa 26 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14681825 CERS1 14253 10715 Epilepsy, progressive myoclonic 8 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19243074; 24782409 CERS3 23752 204219 Ichthyosis, congenital, autosomal recessive 9 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23549421; 23754960 CERT1 2205 10087 Mental retardation, autosomal dominant 34 AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25533962 CES1 1863 1066 Drug metabolism, altered, CES1-related (Carboxylesterase 1 deficiency) AD/AR N/A N/A Biochemical Pharmacogenomic Selection and dosing of certain medications may be affected by the presence of variants 18485328; 23111421; 26817948; 27614009; 28087982 CETP 1869 1071 Hyperalphalipoproteinemia 1 AD/AR N/A N/A Cardiovascular General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6738363; 3937535; 3867663; 2215607; 8675707; 12080388; 12499392; 15840744; 16049032; 17952847; 18354102; 19060911; 19428034; 20686565; 21354572; 21488146; 22122993; 22339301 CFAP251 28506 144406 Spermatogenic failure 33 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30122540; 30122541 CFAP298 1301 56683 Ciliary dyskinesia, primary 26 AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 24094744 CFAP410 1260 755 Retinal dystrophy with or without macular staphyloma; Spondylometaphyseal dysplasia, axial AR N/A N/A Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23105016; 26167768; 26294103;26974433; 26992781; 27548899 CFAP43 26684 80217 Spermatogenic failure 19 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28552195 CFAP44 25631 55779 Spermatogenic failure 20 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28552195 CFAP47 26708 286464 Spermatogenic failure, X-linked, 3 XL N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33472045 CFAP53 26530 220136 Heterotaxy, visceral, 6, autosomal recessive AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Pulmonary The condition can involve multiple congenital anomalies Pulmonary surveillance may be beneficial to assess respiratory function and institute early management; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 22577226; 25504577 CFAP57 26485 149465 van der Woude syndrome 2 AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11781685; 21574244 CFAP58 26676 159686 Spermatogenic failure 49 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32791035 CFAP65 25325 255101 30686508; 31413122; 31501240; 31571197 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30686508; 31413122; 31571197 CFAP69 26107 79846 Spermatogenic failure 24 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29606301 CFAP70 30726 118491 Spermatogenic failure 41 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31621862 CFAP91 24010 89876 Spermatogenic failure 51 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32161152 CFB 1037 629 Hemolytic uremic syndrome, atypical, susceptibility to, 4; Complement factor B deficiency AD/AR Pediatric Allergy/Immunology/Infectious; Hematologic; Renal Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic; Renal In hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications); In Complement factor B deficiency, individuals may manifest with severe and recurrent infections due to encapsulated bacteria, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 6903190; 6898304; 7452889; 16518403; 16936732; 17182750; 20301541; 24152280 CFC1 18292 55997 Heterotaxy, visceral, 2, autosomal dominant AD N/A N/A Cardiovascular; Gastrointestinal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11062482; 11562933; 11799476; 18538293 CFD 2771 1675 Complement factor D deficiency AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may manifest with increased susceptibility to bacterial infections (especially Neisseria), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 11457876; 16527897 CFH 4883 3075 Hemolytic uremic syndrome, atypical; Complement factor H deficiency AD/AR Pediatric Allelic with Basal laminar drusen (AR) Allergy/Immunology/Infectious; Hematologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic; Renal In Hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications); In Complement factor H deficiency, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 646435; 6461667; 2950269; 2966809; 7742208; 9312129; 2966809; 9811382; 9848786; 9551389; 10577907; 10975323; 10762557; 0803850; 11170895; 14583443; 12697737; 14978182; 14583443; 16299065; 16621965; 16612335; 17018561; 18268093; 21784901 CFHR1 4888 3078 Hemolytic-uremic syndrome, atypical, susceptibility to AD/AR/Digenic Pediatric Hematologic; Renal Hematologic; Pharmacogenomic; Renal Deletions related to hemolytic-uremic syndrome involve a contiguous deletion with CFHR1 In Hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications) 98489; 17367211; 18006700; 19435718; 20301541 CFHR3 16980 10878 Hemolytic-uremic syndrome, atypical, susceptibility to AD/AR/Digenic Pediatric Hematologic; Renal Hematologic; Pharmacogenomic; Renal Deletions related to hemolytic-uremic syndrome involve a contiguous deletion with CFHR3 or CFHR4 In Hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications) 16998489; 17367211; 18006700; 20694013; 20301541 CFHR4 16979 10877 Hemolytic-uremic syndrome, atypical, susceptibility to AD/AR/Digenic Pediatric Hematologic; Renal Hematologic; Pharmacogenomic; Renal Deletions related to hemolytic-uremic syndrome involve a contiguous deletion with CFHR3 or CFHR4 In Hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications) 19861685; 20301541 CFHR5 24668 81494 CFHR5 deficiency AD N/A N/A Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20800271; 22503529 CFI 5394 3426 Hemolytic uremic syndrome, atypical; Complement factor I deficiency AD/AR Pediatric Allergy/Immunology/Infectious; Hematologic; Renal Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic; Renal In Hemolytic-uremic syndrome, atypical, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy, eculizumab), as well as decision to perform renal transplant, may be dictated by genetic diagnosis (though renal transplant has been described as not uniformly successful), and certain agents/precipitating factors should be avoided (eg, certain medications); In Complement factor I deficiency, antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; Medical considerations relevant for Hemolytic uremic syndrome (caused by variants in the same gene) may also be important for individuals diagnosed with Complement factor I deficiency 4188976; 4097977; 4507613; 849647; 7922290; 8613545; 15173250; 16412054; 16175037; 16621965; 16386793; 22903728 CFL2 1875 1073 Nemaline myopathy 7 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17160903 CFP 8864 5199 Properdin deficiency, X-linked XL Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals are especially susceptible to Neisseria infections, warranting infectious prophylaxis and early and aggressive treatment of infections 8530058; 8871668; 10909851; 22229731 CFTR 1884 1080 Cystic fibrosis AR Pediatric Allelic with Congenital bilateral absence of the vas deferens (AR) Allergy/Immunology/Infectious; Endocrine; Gastrointestinal; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Endocrine; Gastrointestinal; Pulmonary Early and aggressive multisystem management of pulmonary (with attention to infectious risks), pancreatic, and other manifestations can reduce morbidity and mortality; In the instance of specific variants, targeted therapy (eg, ivacaftor) has been described as beneficial 5657013; 2296270; 1870650; 1284639; 1359500; 7678316; 7680769; 7739684; 7529962; 7539210; 9003498; 9395429; 9113931; 9150159; 9550361; 18685558; 9725921; 11134427; 12768409; 15948195; 17018651; 16778595; 17202412; 7413420; 18685558; 21083385; 21184098; 22047557; 22383668; 22942289; 23590265; 23616732; 23616952; 23757359; 23952705; 24004658; 24039402 CHAMP1 20311 283489 Mental retardation, autosomal dominant 40 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25533962; 26340335 CHAT 1912 1103 Myasthenic syndrome, congenital 6, presynaptic AR Pediatric Musculoskeletal; Neurologic Musculoskeletal; Neurologic; Pharmacogenomic Prophylactic medications (anticholinesterase therapy) in order to prevent apneic episodes/sudden respiratory insufficiency secondary to fever/infections can be effective; Most individuals benefit from AChE inhibitors and/or potassium channel blockers , though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes. Some individuals may be treated with quinidine, which has some major side effects and may be detrimental in individuals with AChR deficiency; In severely affected individuals, diagnosis may be difficult due to the presence of failure to thrive, apneic episodes, and aspiration; Certain medications affecting neuromuscular transmission should be avoided 11172068; 12756141; 20301347 CHCHD10 15559 400916 Myopathy, isolated mitochondrial, autosomal dominant AD Pediatric Allelic with Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (AD); Spinal muscular atrophy, Jokela type (AD) Musculoskeletal; Neurologic Musculoskeletal The condition may manifest with muscle weakness, and medical management (with steroids) has been reported as beneficial 9324076; 21715705; 24934289; 25113787; 25193783; 25428574 CHCHD2 21645 51142 Parkinson disease 22, autosomal dominant AD Pediatric Neurologic Neurologic Response to levodopa has been described 25662902 CHD1 1915 1105 Pilarowski-Bjornsson syndrome AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28866611 CHD2 1917 1106 Develomental and epileptic encephalopathy 94 AD N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23020937 CHD3 1918 1107 Snijders Blok-Campeau syndrome AD N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29463886; 30397230 CHD4 1919 1108 Sifrim-Hitz-Weiss syndrome AD Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic Audiologic/Otolaryngologic Among other features, the condition can include hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 21743468; 27479907; 27616479 CHD7 20626 55636 CHARGE syndrome; Hypogonadotropic hypogonadism 5 with or without anosmia AD Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Musculoskeletal; Neurologic; Renal; Genitourinary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Renal; Genitourinary In CHARGE syndrome, awareness of the potential for cardiovascular, renal, and genitourinary manifestations may allow surveillance and prompt treatment, and awareness of the risk of infections (T-cell abnormalities have been described in some individuals) may benefit efficient treatment of infectious sequelae; Awareness of the risk of hearing impairment may allow prompt detection and treatment aimed at speech and language development; In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to male fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 15300250; 16155193; 16400610; 17661815; 7334995; 17937444; 17684005; 18241060; 18074359; 18834967; 18978652; 18445044; 9375527; 19021638; 20301509; 22724017; 25985275 CHD8 20153 57680 Autism, susceptibility to 18 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21572417; 22495306; 22495309; 22495311; 22521361; 23160955; 24998929 CHEK2 16627 11200 Li-Fraumeni syndrome 2 AD/AR Adult Oncologic Oncologic Variants may be associated with susceptibility to a number of different cancer types Surveillance for neoplasms (eg, breast cancer screening with MRI) may allow preventive measures (eg, with tamoxifen chemoprevention in the case of breast cancer) and early treatment, resulting in improved outcome of malignancies 10617473; 11719428; 11479205; 11967536; 12094328; 12533788; 12690581; 15122511; 15492928; 15087378; 15466005; 15239132; 16257342; 12690581; 17085682; 16551709; 16835864; 18178638; 22058428; 22114986; 21787115; 22006311; 21807500; 22201027; 22072393; 21956126 CHIT1 1936 1118 Chitotriosidase deficiency AR N/A N/A Biochemical General Variants may have implications for monitoring (including related to therapy) in Gaucher disease; Testing relevant to Gaucher disease, if necessary, would be tested as part of care 8132768; 9748235; 16972172; 17464953; 17693102; 15900564; 15528158; 22959626 CHKB 1938 1120 Muscular dystrophy, congenital, megaconial type AR Pediatric Cardiovascular; Dermatologic; Musculoskeletal; Neurologic Cardiovascular The condition can include cardiac sequelae (eg, cardiomyopathy and arrhythmias), and surveillance (eg, with echocardiogram and electrocardiogram) can allow potentially beneficial medical interventions 9427222; 21665002; 22782513; 24997086 CHM 1940 1121 Choiroideremia XL N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2886237; 1302003; 1598901; 8477262; 7981671; 12827496; 19764077; 20301511; 22965595; 24913019 CHMP1A 8740 5119 Pontocerebellar hypoplasia, type 8 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23023333 CHMP2B 24537 25978 Frontotemporal dementia and/or amyotrophic lateral sclerosis 7; Dementia, familial, nonspecific AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8541850; 12451202; 16041373; 16954699; 16807408; 17956895; 20352044; 20592581; 21222599; 22422914; 23142962; 23155438 CHMP4B 16171 128866 Cataract 31, multiple types AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10682967; 10909854; 17701905 CHN1 1943 1123 Duane retraction syndrome 2 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18653847; 21555619; 21715346 CHP1 17433 11261 Spastic ataxia 9, autosomal recessive AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29379881 CHRDL1 29861 91851 Megalocornea 1, X-linked XL Pediatric Ophthalmologic Ophthalmologic Individuals may be at risk for manifestations such as cataract development and glaucoma after lenticular dislocation or subluxation, and awareness may allow early management of sequelae 2571565; 22284829; 24073597; 25093588 CHRM3 1952 1131 Prune belly syndrome (Eagle-Barrett syndrome) AR N/A N/A Genitourinary; Musculoskeletal; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14797335; 15912376; 22077972; 31441039 CHRNA1 1955 1134 Myasthenic syndrome, congenital, 1A, slow-channel; Myasthenic syndrome, congenital, 1B, fast-channel AD/AR Pediatric Allelic with Multiple pterygium syndrome, lethal type (AR) Musculoskeletal; Neurologic Musculoskeletal; Neurologic; Pharmacogenomic Manifestations have been reported in heterozygotes Most individuals with CMS benefit from AChE inhibitors and/or potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; For Slow-channel congenital myasthenic syndrome, effective treatment has been reported with therapies such as quinidine, fluoxetine, and ephedrine, while cholinesterase inhibitors and amifampridine should be avoided; Additional neurologic monitoring in pregnancy may be beneficial 7254233; 3651795; 7863154; 7619526; 8872460; 9158151; 9221765; 10195214; 12588888; 15079006; 16685696; 18806275; 18252226; 20301347; 23108489; 25792100 CHRNA2 1956 1135 Epilepsy, nocturnal frontal lobe, type 4 AD N/A N/A Neurologic General As the attacks had been interpreted in some instances as being nightmares/sleep walking, genetic diagnosis may be helpful Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16826524; 20301348 CHRNA3 1957 1136 Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary congenital anomalies of the kidney and urinary tract AR Pediatric Neurologic; Renal Renal The condition can involve chronic kidney disease andrecurrent urinary tract infections, and awareness may allow prompt diagnosis and management (of note, surgical management of VUR has not been reported as effective) 31708116 CHRNA4 1958 1137 Epilepsy, nocturnal frontal lobe, type 1 AD N/A N/A Neurologic General Mildly affected individuals have been described as frequently undiagnosed/misdiagnosed as nightmares/other sleep disorders, and thus genetic diagnosis may be helpful Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7647781; 7550350; 10563623; 14623738; 20301348; 21753767 CHRNA7 1960 1139 Neurocognitive dysfunction with distinctive craniofacial features AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22775350 CHRNB1 1961 1140 Myasthenic syndrome, congenital, 2A, slow-channel; Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency AD/AR Pediatric Musculoskeletal; Neurologic Musculoskeletal; Neurologic; Pharmacogenomic Most individuals with CMS benefit from AChE inhibitors and/or potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; For Slow-channel congenital myasthenic syndrome, effective treatment has been reported with therapies such as quinidine, fluoxetine, and ephedrine, while cholinesterase inhibitors and amifampridine should be avoided 8872460; 8651643; 10562302; 20301347; 25792100 CHRNB2 1962 1141 Epilepsy, nocturnal frontal lobe, type 3 AD N/A N/A Neurologic General As the attacks had been interpreted in some instances as being nightmares/sleep walking, a genetic diagnosis may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11062464; 20301348 CHRND 1965 1144 Myasthenic syndrome, congenital, 3A, slow-channel; Myasthenic syndrome, congenital, 3B, fast-channel; Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency AD/AR Pediatric Allelic with Multiple pterygium syndrome, lethal type (AR) Musculoskeletal; Neurologic Musculoskeletal; Neurologic; Pharmacogenomic Most individuals with Myasthenic syndrome, congenital benefit from AChE inhibitors and/or potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; For Slow-channel congenital myasthenic syndrome, effective treatment has been reported with therapies such as quinidine, fluoxetine, and ephedrine, while cholinesterase inhibitors and amifampridine should be avoided; Additional neurologic monitoring in pregnancy may be beneficial 11435464; 11782989; 18252226; 12499478; 16916845; 18398509; 23108489; 25792100 CHRNE 1966 1145 Myasthenic syndrome, congenital, 4A, slow-channel; Myasthenic syndrome, congenital, 4B, fast-channel; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency AD/AR Pediatric Musculoskeletal; Neurologic Musculoskeletal; Neurologic; Pharmacogenomic Most individuals with Myasthenic syndrome, congenital, benefit from AChE inhibitors and/or potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; For Slow-channel congenital myasthenic syndrome, effective treatment has been reported with therapies such as quinidine, fluoxetine, and ephedrine, while cholinesterase inhibitors and amifampridine should be avoided; Additional neurologic monitoring in pregnancy may be beneficial 8232384; 7538206; 7531341; 8957026; 8872460; 8755487; 9158150; 0514102; 10211467; 10962020; 10534268; 11030414; 12141316; 12034803; 15322984; 16087917; 19064877; 20301347; 20562457; 23108489; 25792100 CHRNG 1967 1146 Multiple pterygium syndrome, lethal type; Escobar syndrome AR N/A N/A Craniofacial; Musculoskeletal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16826520; 16826531; 22167768; 25608830 CHST11 17422 50515 Osteochondrodysplasia, brachydactyly, and overlapping malformed digits AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26436107; 29514872 CHST14 24464 113189 Ehlers-Danlos syndrome, musculocontractural type 1 AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic Hematologic; Musculoskeletal; Ophthalmologic Clinical issues relate to connective tissue fragility may affect multiple organs, and may include severe bleeding episodes (eg, after minor trauma), such that recognition may allow precautions and preventive measures, as well as rapid treatment in the case of bleeding; Medical treatment (eg, with oral dermatan sulfate) may be beneficial; Due to risk of glaucoma, surveillance may allow early management 9084938; 10766984; 11370633; 16158441; 20004762; 20503305; 20842734; 20533528; 21744491; 22581468; 22407744; 22987394; 23704329 CHST3 1971 9469 Spondyloepiphyseal dysplasia with congenital joint dislocations AR N/A N/A Cardiovascular; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 112567; 9039660; 15368507; 15098240; 15215498; 17618475; 18513679; 18698629; 19320654; 20830804; 22539336 CHST6 6938 4166 Macular dystrophy, corneal AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8684802; 11017086; 11818380; 16207214; 16568029; 17093400; 17896316; 17962390; 19223992; 19365571; 21242781; 21887843; 26604660 CHST8 15993 64377 Peeling skin syndrome 3 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22289416 CHSY1 17198 22856 Temtamy preaxial brachydactyly syndrome AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic Audiologic/Otolaryngologic The condition can include hearing loss, as well as other features and may frequently be clinically recognizable Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 9823490; 21129728; 19952732; 21129727 CHUK 1974 1147 Fetal encasement syndrome (Cocoon syndrome); Bartsocas-Papas syndrome 2 AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic; Pulmonary; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20961246; 25691407 CIB1 16920 10519 Epidermodysplasia verruciformis, susceptibility to, 3 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Oncologic Oncologic Among other findings, individuals have been described as being at increased risk of nonmelanoma skin cancer (as well as other skin neoplasms), and awareness have allowed increased surveillance and management 28646613; 30068544 CIB2 24579 10518 Deafness, autosomal recessive 48; Usher syndrome type IJ AR Pediatric Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 18505454; 23023331 CIBAR1 30452 137392 Polydactyly, postaxial, type A9 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30395363 CIC 14214 23152 Mental retardation, autosomal dominant 45 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28288114 CIDEC 24229 63924 Lipodystrophy, familial partial, type 5 AR Pediatric Cardiovascular; Endocrine; Gastrointestinal Cardiovascular; Endocrine; Gastrointestinal Medical treatment of factors such as diabetes, hypertension, and lipid abnormalities may be beneficial to reduce morbidity/mortality; Recognition and treatment of hypertriglyceridemia can help avoid sequelae such as acute pancreatitis 20049731 CIITA 7067 4261 Bare lymphocyte syndrome, type II AR Pediatric Allergy/Immunology/Infectious; Gastrointestinal Allergy/Immunology/Infectious Prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been reported in Bare lymphocyte syndrome, type II 8402893; 9099848; 11862382 CILK1 21219 22858 Epilepsy, juvenile myoclonic, susceptibility to, 10; Endocrine-cerebroosteodysplasia AD/AR N/A N/A Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19185282; 29539279 CISD2 24212 493856 Wolfram syndrome 2 AR Pediatric Audiologic/Otolaryngologic; Endocrine; Gastrointestinal; Genitourinary; Hematologic; Ophthalmologic; Renal Gastrointestinal; Genitourinary; Hematologic; Renal Urinary tract anomalies can lead to severe (and potentially avoidable) renal sequelae, including renal failure, and surveillance and early management can be beneficial; Surveillance for and early treatment of bleeding diatheses (as well as related GI disease that can lead to bleeding) can be beneficial 10739754; 11317648; 12116178; 17846994; 22790102; 23429432; 25056293 CIT 1985 11113 Microcephaly 17, primary, autosomal recessive AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27453578; 27453579; 27503289; 27519304 CITED2 1987 10370 Atrial septal defect 8; Ventricular septal defect 2 AD N/A N/A Cardiovascular General Variants may be involved in Premature ovarian failure (AD), but the evidence is unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16287139; 20654020; 22709740; 23082118 CIZ1 16744 25792 Primary cervical dystonia, adult-onset AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22447717 CKAP2L 26877 150468 Filippi syndrome AR N/A N/A Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15365457; 18553552; 25439729 CLAM 20394 373073 Pontocerebellar hypoplasia, type 3 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12771259; 25832664 CLCC1 29675 23155 Retinitis pigmentosa 32 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16189710; 30157172 CLCF1 17412 23529 Crisponi/Cold-induced sweating syndrome 2 AR Pediatric Musculoskeletal; Neurologic Neurologic In the neonatal/early childhood period, the condition can be lethal unless advanced care is instituted; Later, it has been described that cold-induced sweating was alleviated by medical treatment (eg, with clonidine, with lasting effects when co-administered with amitriptyline) 16782820; 20400119 CLCN1 2019 1180 Myotonia congenita, autosomal dominant; Myotonia congenita, autosomal recessive, Myotonia levior AD/AR Pediatric Musculoskeletal Musculoskeletal; Pharmacogenomic Individuals may be at increased risk of potentially avoidable/manageable anesthesia reactions, and the disorder may not be clinically highly obvious prior to severe sequelae; Muscle stiffness may respond to medical treatment (eg, mexiletine, tocainide, procainamide, quinine, or phenytoin, as well as other agents); Depolarizing muscle relaxants (eg, suxamethonium), and other agents (eg, adrenaline, beta-adrenergic agonists, propranolol, colchicine) may aggravate myotonia 1670657; 1379744; 7981750; 7951242; 8112288; 7581380; 9040658; 11113225; 11840191; 11933197; 12390967; 12699527; 14639587; 15786415; 17932099; 19185184; 18337100; 20842486; 20301529; 21221019 CLCN2 2020 1181 Hyperaldosteronism, familial, type II AD Pediatric Allelic with Epilepsy, idiopathic, generalized, susceptibility to, 11 (AD); Leukoencephalopathy with ataxia (AR) Endocrine; Neurologic Endocrine Functional proof of pathogenicity in reported epilepsy-related dominant conditions is controversial; As with other forms of epilepsy, optimal seizure control is advantageous The condition may manifest with features of hyperadolsteronism including hypertension and hypokalemia, and awareness may allow prompt medical management (eg, with spironolactone) 10888596; 12612585; 19710712; 19191339; 20037607; 23707145; 29403011; 29403012 CLCN4 2022 1183 Raynaud-Claes syndrome XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8826458; 9415477; 23647072; 25644381 CLCN5 2023 1184 Dent disease 1; Hypophosphatemic rickets, X-linked recessive; Nephrolithiasis, type I; Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis XL Pediatric Endocrine; Renal Endocrine; Pharmacogenomic; Renal In Dent disease, surveillance and treatment related to manifestations such as hypercalciuria in order to prevent kidney stones, nephrocalcinosis, and to delay the progression of kidney dysfunction may be beneficial (though efficacy is unclear, treatment may include thiazide diuretics, ACE inhibitors, and ARBs); Vitamin D and phosphorous may be beneficial related to skeletal manifestations; Growth hormone may be indicated; Nephrotoxic agents (eg, NSAIDs, aminoglycosides) should be avoided 14169453; 1908057; 1372109; 7915957; 7922301; 8559248; 9328929; 9062355; 9328927; 9187673; 602200; 15086899; 19673950; 22876375 CLCN6 2024 1185 Neurodegeneration, childhood-onset, hypotonia, respiratory insufficiency and brain imaging abnormalities AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33217309 CLCN7 2025 1186 Osteopetrosis, autosomal dominant 2; Osteopetrosis, autosomal recessive 4 AD/AR Pediatric Allelic with Hypopigmentation, organomegaly, and delayed myelination and development (AD) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Allergy/Immunology/Infectious; Hematologic; Musculoskeletal In Autosomal recessive osteopetrosis, early diagnosis can allow medical treatment related to calcium homeostasis, including prevention/treatment of hypocalcemic seizures; Transfusions for hematologic manifestations may be necessary; Individuals may benefit from infectious prophylaxis and early and aggressive treatments of infections; HSCT has been described as beneficial; In Autosomal dominant forms of Osteopetrosis, avoidance of high-fracture risk activities can be beneficial, and calcitriol has been reported as beneficial 18131787; 13665485; 4871758; 6546410; 3377922; 2268972; 8358946; 10617161; 11741829; 11207362; 12522560; 13130312; 14584882; 17033731; 17164308; 20301306; 23296056; 31155284 CLCNKA 2026 1187 Bartter syndrome, type 4, digenic AR/Digenic Pediatric Audiologic/Otolaryngologic; Renal Audiologic/Otolaryngologic; Renal Digenic inheritance (with CLCNKB) has been described Due to renal salt wasting, individuals can present with dehydration and life-threatening hypotension, and electrolyte management can be beneficial; In some forms, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 15044642; 18310267 CLCNKB 2027 1188 Bartter syndrome, type 3; Bartter syndrome, type 4, digenic AR/Digenic Pediatric Audiologic/Otolaryngologic; Renal Audiologic/Otolaryngologic; Renal Digenic inheritance (with CLCNKA) has been described Due to renal salt wasting, individuals can present with dehydration and life-threatening hypotension, and electrolyte management can be beneficial; In some forms, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 13969763; 9326936; 11102542; 15044642; 18310267; 21162973; 20931281; 19807735; 21479528; 21631963 CLDN1 2032 9076 Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis AR N/A N/A Dermatologic; Gastrointestinal Gastrointestinal Individuals can have manifest with hepatic disease, and liver transplantation has been described as beneficial; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12164927; 15521008; 16619213; 20645982; 21865982 CLDN10 2033 9071 Hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, icthyosis, and xerostomia (HELIX syndrome) AR Pediatric Dental; Dermatologic; Renal Renal Among other findings, patients may have electrolyte abnormalities, and identification may allow early management 28686597; 28771254 CLDN11 8514 5010 Leukodystrophy, hypomyelinating, 22 AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33313762 CLDN14 2035 23562 Deafness, autosomal recessive 29 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 11163249; 22246673 CLDN16 2037 10686 Hypomagnesemia 3, renal AR Pediatric Renal Renal Some individuals have a self-limiting form of disease Presentation can include hypocalcemic/hypomagnesemic seizures, and early diagnosis and magnesium therapy can be beneficial; Renal transplantation is frequently necessary 668721; 7637271; 9579153; 10390358; 10878661; 14628289; 16501001; 20607983; 21669885; 21848011; 22422540 CLDN19 2040 149461 Hypomagnesemia 5, renal, with ocular involvement AR Pediatric Ophthalmologic; Renal Renal Electrolyte replacement and surveillance for sequelae such as urinary tract infections can be beneficial 500385; 7947033; 17033971; 21030577; 21791920; 22422540; 23301036; 23538362 CLDN2 2041 9075 Azoospermia, obstructive, with nephrolithiasis XL N/A N/A Genitourinary; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31320686 CLDN9 2051 9080 Deafness, autosomal recessive 116 AR N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31175426 CLEC7A 14558 64581 Candidiasis, familial, 4 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Heterozygous variants may result in milder manifestations Individuals are highly susceptible to recurrent fungal infections, and recognition may allow prompt treatment, which may be beneficial 18946062; 19864674; 20807886; 20107226; 22674328; 23374272 CLIC2 2063 1193 Mental retardation, X-linked, syndromic 32 XL Adult Cardiovascular; Musculoskeletal; Neurologic Cardiovascular Among other manifestations, individuals have been described as including cardiac findings such as atrial fibrillation, congestive heart failure, valvular insufficiency, and awareness may allow surveillance and early medical management 22814392 CLIC5 13517 53405 Deafness, autosomal recessive 103 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 24781754 CLMP 24039 79827 Congenital short bowel syndrome AR Pediatric Gastrointestinal Gastrointestinal Individuals have been described as benefiting from early introduction of enteral feeds, with later weaning from parenteral nutrition; Awareness of the risk of other GI-related complications may allow prompt recognition and management 2005514; 10532268; 16707984; 18209785; 22155368 CLN3 2074 1201 Ceroid lipofuscinosis, neuronal, 3 AR Pediatric Biochemical; Neurologic; Ophthalmologic Neurologic Levodopa treatment may be beneficial 7426545; 1609833; 1319116; 7553855; 7887420; 9004140; 9311735; 9450775; 10477428; 11342698; 15965709; 17947292; 19135632; 19489875; 21990111 CLN5 2076 1203 Ceroid lipofuscinosis, neuronal, 5 AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7133332; 1649978; 9662406; 15965709; 15728307; 17607606; 19309691; 20157158; 25359263 CLN6 2077 54982 Ceroid lipofuscinosis, neuronal, 6; Ceroid lipofuscinosis, neuronal, 4A, autosomal recessive AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13822848; 5478271; 760366; 3284607; 7668317; 10929274; 11791207; 11727201; 15965709; 15996215; 19520283; 21549341; 21990111; 22883287; 23180398; 23735787; 30561534 CLN8 2079 2055 Ceroid lipofuscinosis, neuronal, 8; Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10508524; 10191125; 11589000; 15024724; 15074367; 16570191; 17129765; 17560505; 19431184; 19807737; 21990111; 22220808; 22964447 CLP1 16999 10978 Pontocerebellar hypoplasia type 10 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24766809; 24766810; 29307788 CLPB 30664 81570 3-methylglutaconic aciduria, type VII AR Pediatric Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Endocrine; Hematologic; Neurologic; Oncologic; Ophthalmologic Allergy/Immunology/Infectious; Oncologic The condition can involve neutropenia, with recurrent/severe infections in some, and awareness may allow early and aggressive management of infections; Indidivuals have been reported with leukemia, and awareness may allow eaerly diagnosis and management 25597510; 25597511; 25650066 CLPP 2084 8192 Perrault syndrome 3 AR Pediatric Audiologic/Otolaryngologic; Endocrine; Neurologic; Obstetric Audiologic/Otolaryngologic; Obstetric Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Genetic knowledge may allow fertility preservation such as by storing eggs 17690910; 22037954; 23541340 CLPX 2088 10845 Protoporphyria, erythropoietic, 2 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28874591 CLRN1 12605 7401 Retinitis pigmentosa 61; Usher sydnrome, type 3A AR N/A N/A Audiologic/Otolaryngologic; Ophthalmologic General Hearing loss has been reported to be postlingual Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7711740; 8975700; 9719374; 11524702; 12080385; 12145752; 14569126; 15521980; 19753315; 21310491; 21675857 CLRN2 33939 645104 Deafness, autosomal recessive 117 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 33496845 CLTC 2092 1213 Mental retardation, autosomal dominant, 56 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26822784; 29100083; 31961069 CNBP 13164 7555 Myotonic dystrophy 2 AD Pediatric Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Obstetric; Ophthalmologic Cardiovascular Individuals with bi-allelic variants and severe cardiac manifestations have been described The condition can include cardiovascular manifestions, including arrhythmias (sudden cardiac death has been reported), left ventricular dysfunction, and congestive heart failure, and surveillance (eg, with EKG and echocardiogram), as well as early interventions and medical management, may decrease morbidity and mortality 10078095; 11486088; 12970845; 12601109; 14505273; 15503094; 15503094; 15623712; 16258778; 16684600; 18057971; 19020295; 19481939; 20301639; 20627570; 22587749; 23561036 CNGA1 2148 1259 Retinitis pigmentosa 49 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7479749 CNGA3 2150 1261 Achromatopsia 2; Leber congenital amaurosis AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9662398; 11536077; 15059731; 15980212; 16961972; 18636117; 20454696; 21901789; 21911670; 21912902; 23362848; 25616768 CNGB1 2151 1258 Retinitis pigmentosa 45 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11379879; 15557452; 20126465 CNGB3 2153 54714 Achromatopsia 3; Macular degeneration, juvenile AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4192495; 1347967; 10888875; 15712225; 17265047; 17652762; 19767295; 20454696; 23362848 CNKSR2 19701 22866 Mental retardation, X-linked, syndromic, Houge type XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25223753; 28098945 CNNM2 103 54805 Hypomagnesemia 6, renal AR Pediatric Allelic with Hypomagnesemia, seizures, and mental retardation 1 (AD/AR) Neurologic; Renal Renal In Hypomagnesemia, seizures, and mental retardation 1, magnesium supplementation has not been described as effective Correction of electrolyte abnormalities may help treatment, though complete correction was not achieved in some described individuals 12584272; 21397062; 24699222 CNNM4 105 26504 Jalili syndrome AR N/A N/A Dental; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3236352; 15173235; 19200525; 19200527; 20706282 CNOT1 7877 23019 Holoprosencephaly 12, with or without pancreatic agenesis AD Pediatric Allelic with Vissers-Bodmer syndrome (AD) Audiologic/Otolaryngologic; Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic Audiologic/Otolaryngologic; Endocrine In addition to other findings, the condition has been described as sometimes involving congenital absence of the pancreas, which leads to medical interventions to manage early-onset insulin-dependent diabetes mellitus and the need for pancreatic enzyme replacement; In some individuals, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 28525974; 31006510; 32553196 CNOT2 7878 4848 Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31145527; 31512373 CNOT3 7879 4849 Intellectual developmental disorder with speech delay, autism, and dysmorphic facies AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31201375 CNP 2158 1267 Leukodystrophy, hypomyelinating, 20 AR N/A N/A Craniofacial; Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32128616 CNPY3 11968 10695 Developmental and epileptic encephalopathy 60 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29394991 CNTN1 2171 1272 Myopathy, congenital, Compton-North AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12899872; 19026398 CNTN2 2172 6900 Epilepsy, familial adult myoclonic 5 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23518707 CNTNAP1 8011 8506 Lethal congenital contracture syndrome 7; Neuropathy, congenital hypomyelinating, 3 AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24319099; 27782105; 27668699; 28374019; 29511323 CNTNAP2 13830 26047 Cortical dysplasia-focal epilepsy syndrome (Pitt-Hopkins like syndrome 1) AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16571880; 19896112; 19582487 COA3 24990 28958 Mitochondrial complex IV deficiency, nuclear type 14 AR N/A N/A Biochemical; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25604084 COA5 33848 493753 Mitochondrial complex IV, deficiency, nuclear type 9 AR N/A N/A Biochemical; Cardiovascular General Manifestations include lethal neonatal hypertrophic cardiomyopathy Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21457908 COA6 18025 388753 Mitochondrial complex IV deficiency, nuclear type 13 AR N/A N/A Biochemical; Cardiovascular; Neurologic General Manifestations include lethal neonatal hypertrophic cardiomyopathy Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22277967; 24549041; 25339201 COA7 25716 65260 Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27683825; 29718187 COA8 20492 84334 Mitochondrial complex IV deficiency, nuclear type 17 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25175347 COASY 29932 80347 Neurodegeneration with brain iron accumulation 6; Pontocerebellar hypoplasia, type 12 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24360804; 30089828 COCH 2180 1690 Deafness, autosomal recessive 110 AR Pediatric Allelic with Deafness, autosomal dominant 9 (AD) Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language developmen 8817345; 9806553; 10400989; 14512963; 16261627; 18312449; 19161137; 20447147; 21046548; 21052762; 21774451; 22610276; 22931125; 29449721 COG1 6545 9382 Congenital disorder of glycosylation, type IIg AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic Hematologic The condition can include cardiac manifestations as well as other multi-system manifestations; Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 16537452; 19008299 COG2 6546 22796 Congenital disorder of glycosylation, type IIq AR Pediatric Biochemical; Gastrointestinal; Hematologic; Neurologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 24784932 COG4 18620 25839 Congenital disorder of glycosylation, type IIj AR Pediatric Allelic with Saul-Wilson syndrome (AD) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Craniofacial; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Allergy/Immunology/Infectious; Hematologic Hepatic-metabolized agents should be avoided The condition can include recurrent respiratory infections as well as other multi-systemic manifestations, and precautions may be beneficial; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 19494034; 30290151 COG5 14857 10466 Congenital disorder of glycosylation, type IIi AR Pediatric Audiologic/Otolaryngologic; Biochemical; Hematologic; Neurologic; Ophthalmologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 19690088; 23228021; 31572517; 32174980 COG6 18621 57511 Congenital disorder of glycosylation, type IIl AR Pediatric Allelic with Shaheen syndrome (AR) Allergy/Immunology/Infectious; Biochemical; Craniofacial; Dental; Dermatologic; Gastrointestinal; Hematologic; Neurologic Allergy/Immunology/Infectious; Hematologic Hepatic-metabolized agents should be avoided The condition can include recurrent infections as well as other multi-systemic manifestations, and awareness may allow preventive measures as well as early and aggressive treatment of infections; A described individual presented with neurological manifestations as well as vitamin K deficiency and intracranial bleeding; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 20605848; 23606727 COG7 18622 91949 Congenital disorder of glycosylation, type IIe AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 15107842; 17356545; 19577670 COG8 18623 84342 Congenital disorder of glycosylation, type IIh AR Pediatric Biochemical; Hematologic; Neurologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 17220172; 17331980; 20301507; 30690882 COL10A1 2185 1300 Metaphyseal chondrodysplasia, Schmid type AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14279845; 3281118; 8220429; 7936797; 8782043; 9837818; 10929364; 12554676; 15578582; 14227699; 17403716; 20872587; 21360259; 21447328 COL11A1 2186 1301 Stickler syndrome, type II; Deafness, autosomal dominant, 37; Fibrochondrogenesis; Marshall syndrome AD/AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic Audiologic/Otolaryngologic; Ophthalmologic Though the conditions may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Stickler syndrome, avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated 13520885; 749746; 6694183; 6507479; 6507478; 8733059; 8872475; 9129742; 10573014; 9529347; 9475607; 10486316; 15286167; 17236192; 21035103; 20301479; 30245514; 33169910; 33605226 COL11A2 2187 1302 Deafness, autosomal dominant 13; Otospondylomegaepiphyseal dysplasia, autosomal dominant (Stickler syndrome, type III/Weissenbacher-Zweymuller syndrome); Fibrochondrogenesis 2; Otospondylomegaepiphyseal dysplasia, autosomal recessive; Deafness, autosomal recessive 53 AD/AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic Audiologic/Otolaryngologic; Ophthalmologic Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated 14234962; 7833911; 7859284; 9805126; 9506662; 10581026; 10677296; 15372529; 16033917; 22246659; 25633957 COL12A1 2188 1303 Bethlem myopathy 2; Ullrich congenital muscular dystrophy 2 AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24334604; 24334769 COL13A1 2190 1305 Myasthenic syndrome, congenital, 19 AR Pediatric Craniofacial; Musculoskeletal; Neurologic Musculoskeletal Individuals are affected by muscular weakness, including affecting the respiratory system, and medical management (with 3,4-diaminopyridine and salbutamol) has been reported as beneficial 26626625 COL17A1 2194 1308 Epithelial recurrent erosion dystrophy (ERED); Epidermolysis bullosa, junctional, non-Herlitz type AD/AR N/A N/A Dermatologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2663347; 7883981; 7550320; 9038345; 9403072; 17263807; 17596158; 19369679; 20301304; 21357940; 21466533; 22965308; 25676728 COL18A1 2195 80781 Glaucoma, primary, closed-angle AD Adult Allelic with Knobloch syndrome 1 (AR) Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic Ophthalmologic The condition can involve loss of vision, and awareness of disease risk may allow surveillance and early treatment 1554013; 7802003; 10942434; 14695535; 17546652; 19160445; 20799329; 21085708; 21862674; 21937992; 30007336 COL1A1 2197 1277 Ehlers-Danlos syndrome, classic type, 1; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 AD Pediatric Allelic with Osteogenesis imperfecta, types I, II, III, and IV (AD) (for which medical treatment (eg, with pamidronate) may be beneficial, but evidence does not show that early (genetic) diagnosis would necessarily advantageous in terms of medical treatment); Caffey disease (AD); Ehlers-Danlos syndrome, arthrochalasia type, 1 (AD) Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Musculoskeletal; Obstetric; Ophthalmologic Cardiovascular; Obstetric Individuals with Ehlers-Danlos syndrome, classic type, 1; ay have aortic root dilatation (as well as arterial/vascular fragility), but the natural history is unclear, and many not commonly progress, though yearly surveillance with echocardiogram when aortic dilatation or mitral valve prolapse is peresent has been recommended; Precautions in pregnancy may be beneficial; In Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1, cardiovascular manifestations such as aortic root dilatation have been described, and awareness may allow surveillance and management 1146889; 1054840; 6304100; 3001313; 3016737; 3082886; 3722186; 3940669; 3108247; 3667599; 3403550; 3341380; 2745420; 2511192; 2794057; 2767050; 2777808 ; 2309707; 2121988; 2339700; 2295701; 1867198; 2037280; 1301191; 1353940; 8408653; 7789952; 9007315; 8757037; 8723681; 8613526; 8910493; 9386671; 9295084; 9067755; 9101290; 9143923; 9753709; 9753715; 10417276; 10739762; 10843163; 11286507; 11760017; 11668615; 11970931; 11704682; 12417561; 12417568; 12524541; 12629073; 12728084; 15024692; 15241796; 15728585; 15864348; 16272059; 16291701; 16434452; 16778601; 17078022; 17211858; 17217883; 17309652; 18409203; 18553566; 18996919; 19929435; 20087402; 21667357; 22206639; 22565191; 22791419; 22795108; 22855962; 22987783; 23072183; 23118688; 23682531; 23692737; 28261977 COL1A2 2198 1278 Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2; Ehlers-Danlos syndrome, cardiac valvular form AD/AR Pediatric Allelic with Osteogenesis imperfecta, types II,III, and IV (AD) (for which medical treatment (eg, with pamidronate) may be beneficial, but evidence does not show that early (genetic) diagnosis would necessarily advantageous in terms of medical treatment); Ehlers-Danlos syndrome, arthrochalasia type, 2 (AD) Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Musculoskeletal; Ophthalmologic Cardiovascular Ehlers-Danlos syndrome, cardiac valvular form may be difficult to recognize, and cardiac manifestations, which can include arrhythmias may benefit from early (including surgical) interventions; Some individuals may also have arterial/vascular fragility, and awareness may allow appropriate precautions and prompt management of sequelae; In In Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1, cardiovascular manifestations (eg, aortic dilatation, vascular fragility) have been described, and awareness may allow surveillance and management 4742738; 6773953; 3940669; 2952379; 3621666; 3680255; 2454224; 2897363; 2777808; 1712342; 1301191; 1577745; 7916744; 8071956; 8950681; 9386671; 9295084; 9099837; 9753709; 10843163; 11760017; 11970931; 12417561; 12417568; 12629073; 12728084; 15241796; 15077201; 16778601; 16816023; 16434452; 17217883; 18996919; 19208385; 20087402; 21667357; 22206639; 22791419; 22795120; 23118688; 23692737 COL25A1 18603 84570 Fibrosis of extraocular muscles, congenital 5 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25500261 COL27A1 22986 85301 Steel syndrome AR Pediatric Craniofacial; Musculoskeletal Musculoskeletal Outcomes have been described as better without the use of surgical treatment for hip dislocations 8423186; 24986830 COL2A1 2200 1280 Stickler syndrome, type I; Czech dysplasia; Otospondylomegaepiphyseal dysplasia; Epiphyseal dysplasia, multiple, with myopia and deafness AD Pediatric Allelic with Achondrogenesis, type II (AD); Hypochondrogenesis (AD); Spondyloepimetaphyseal dysplasia, Strudwick type (AD); Spondyloepimetaphyseal dysplasia, Namaqualand type (AD); Spondyloepimetaphyseal dysplasia, Stanescu type (AD); Spondyloepiphyseal dysplasia congenita (AD); Kniest dysplasia (AD); Platyspondylic skeletal dysplasia, Torrance type (AD); Vitreoretinopathy with phalangeal epiphyseal dysplasia (AD); Legg-Calve-Perthes disease (AD); Osteoarthritis with mild chondrodysplasia (AD); Spondyloperipheral dysplasia (AD); Avascular necrosis of femoral head, primary 1 (AD) Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic Audiologic/Otolaryngologic; Ophthalmologic The condition can include varying degrees/types of early hearing loss in some conditions, such as Stickler syndrome and Otospondylomegaepiphyseal dysplasia , while in others, such as Czech dysplasia, the hearing loss typically occurs much later Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated; In Avascular necrosis of femoral head, primary, identifying carriers before the onset of clinical symptoms can allow interventions in order to delay disease progression 14299791; 5582025; 4568361; 4214536; 699354; 514691; 7036745; 6628450; 6496567; 4014370; 3728560; 2572591; 1975693; 2300123; 1677770; 1671807; 1429602; 1444917; 8434604; 8325895; 8317498; 8737653; 7981752; 7700721; 7874117; 7757081; 7550321; 7847372; 8737653; 8723097; 9800905; 10486316; 10406661; 10745044; 10982970; 11812423; 12939326; 12544472; 12884428; 15266623; 15895462; 15316962; 14729840; 15930420; 16189708; 15671297; 15316962; 16088915; 15643621; 17726487; 16752401; 16155195; 17394019; 17437277; 17509551; 17721977; 18553548; 19764028 ; 20131279; 20583175; 20513134; 21671384; 21204228; 20301479; 21924244; 21332586; 20179744; 26183434; 26420734 COL3A1 2201 1281 Ehlers-Danlos syndrome, vascular type; Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome AD/AR Pediatric Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Obstetric Cardiovascular; Obstetric Homozygous variants have been reported; An individual with EDS type III with a COL3A1 variant has been reported Individuals are at risk for manifestations such as bowel and arterial ruptures, as well as severe pregnancy-related complications in women, and surveillance (eg, arterial screening by CT or MRI) and early recognition may allow precautionary measures prompt recognition and treatment of manifestions, which may reduce morbidity and mortality 7230200; 6129381; 3204406; 3337712; 2321591; 2349939; 2243125; 1496983; 1352273; 1557695; 8317500; 7833919; 8526472; 10051163; 10928897; 10706896; 11577371; 12131463; 12786757; 15007000; 19455184; 20301667; 21637106; 22713205; 23052746; 23688910; 24922459; 25205403; 28258187; 28742248 COL4A1 2202 1282 Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps; Brain small vessel disease 1 with or without ocular anomalies; Anterior segment dysgenesis with cerebral involvement; Porencephaly 1; Retinal artery tortuosity; Schizencephaly AD Adult Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic; Renal Cardiovascular; Ophthalmologic; Pharmacogenomic Trauma at birth and during adulthood, as well as issues such as hypertension and exercise-induced stress is a stronger risk factor for intracerebral hemorrhage than in persons without relevant variants; Anticoagulant use may exacerbate the stroke risk associated with COL4A1 variants; Individuals with Retinal artery tortuosity (isolated as part of a more syndromic context) have been described with transient vision loss because of retinal hemorrhage after minor stress (eg, exercise) or trauma, and knowledge may allow preventive measures to avoid retinal hemorrhage 6428250; 12525718; 15136694; 15905400; 15882279; 17030722; 16598045; 18160688; 17696175; 19949034; 19194877; 20056676; 22522439; 23225343; 23394911; 24628545; 25228067; 25719457; 28017902 COL4A2 2203 1284 Hemorrhage, intracerebral, susceptibility to AD Adult Allelic with Brain small vessel disease 2 (AD) Cardiovascular Cardiovascular Authors have suggested that reported nonglycine variants may result in milder disease later in life or cause disease due to interactions with other factors. The awareness that individuals are at risk for hemorrhagic stroke may allow preventive management related to contributory factors, which may decrease morbidity/mortality. 22209247; 22209246 COL4A3 2204 1285 Alport syndrome 3, autosomal dominant; Alport syndrome 2, autosomal recessive AD/AR Pediatric Allelic with Hematuria, benign familial (AD) Audiologic/Otolaryngologic; Ophthalmologic; Renal Ophthalmologic; Renal In Alport syndrome, medical treatment related to renal sequelae (eg, with ACE inhibitors, ARBs) may be beneficial related to delaying renal failure, as well as with overall life expectancy, though dialysis/renal transplantation may be required; Corneal protection may be beneficial in individuals with recurrent corneal erosions 7033680; 7987301; 8196274; 7987396; 7783412; 7783419; 9195222; 9269635; 11961012; 11134255; 20301386; 22166847; 22237748; 22811928; 22997344; 23927549 COL4A4 2206 1286 Alport syndrome 2, autosomal recessive AD/AR Pediatric Allelic with Hematuria, benign familial (AD) Audiologic/Otolaryngologic; Ophthalmologic; Renal Ophthalmologic; Renal In Alport syndrome, medical treatment related to renal sequelae (eg, with ACE inhibitors, ARBs) may be beneficial related to delaying renal failure, as well as with overall life expectancy, though dialysis/renal transplantation may be required; Corneal protection may be beneficial in individuals with recurrent corneal erosions 7033680; 7987396; 7783412; 8787673; 9195222; 20301386; 22166847; 22237748; 22811928; 22997344 COL4A5 2207 1287 Alport syndrome 1, X-linked XL Pediatric Audiologic/Otolaryngologic; Ophthalmologic; Renal Ophthalmologic; Renal Treatment of renal issues (eg, with antihypertensive agents, ACE inhibitors, etc.) can be helpful, but does not appear to affect natural history In Alport syndrome, medical treatment related to renal sequelae (eg, with ACE inhibitors, ARBs) may be beneficial related to delaying renal failure, as well as with overall life expectancy, though dialysis/renal transplantation may be required; Corneal protection may be beneficial in individuals with recurrent corneal erosions 20773074; 14856448; 626446; 7033680; 3728466; 2349482; 1483700; 1635357; 1598909; 7706490; 8825605; 8651292; 8940267; 8651296; 9195222; 20881942; 21505094; 21848006; 21897443; 21332469; 22166944; 20301386; 22166847; 22237748; 22335431; 22811928; 22921432; 22919268; 22997344 COL4A6 2208 1288 Deafness, X-linked 6 XL Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 23714752 COL5A1 2209 1289 Ehlers-Danlos syndrome, classic type, 1 AD Pediatric Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Musculoskeletal; Obstetric; Ophthalmologic Cardiovascular; Obstetric Homozygous variants have been reported Individuals with Ehlers-Danlos syndrome may have aortic root dilatation, but the natural history is unclear, and may not typically progress, though yearly surveillance with echocardiogram when aortic dilatation or mitral valve prolapse is peresent has been recommended; Precautions in pregnancy may be beneficial; Individuals with Fibromuscular dysplasia may have vascular complications, including aneurysms, and early diagnosis may provide early management 8541855; 8923000; 9042913; 10602121; 10777716; 11992482; 12180144; 15264295; 15580559; 18972565; 20635400; 20847697; 20301422; 21611149; 22696272; 32938213 COL5A2 2210 1290 Ehlers-Danlos syndrome, classic type, 2 AD Pediatric Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Musculoskeletal; Obstetric; Ophthalmologic Cardiovascular; Obstetric Individuals may have aortic root dilatation, but the natural history is unclear, and may not typically progress, though yearly surveillance with echocardiogram when aortic dilatation or mitral valve prolapse is peresent has been recommended; Precautions in pregnancy may be beneficial 9425231; 9783710; 12180144; 16278879; 15580559; 20301422; 20847697 COL6A1 2211 1291 Ullrich congenital muscular dystrophy 1; Bethlem myopathy 1 AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 963533; 3632670; 8782832; 11932968; 12840783; 12958705; 16130093; 15689448; 15955946; 17785674; 17886299; 18362356; 18366090; 19564581; 20301676; 20976770 COL6A2 2212 1292 Ullrich congenital muscular dystrophy 1 ; Myosclerosis, congenital; Bethlem myopathy 1; Epilepsy, progressive myoclonic, autosomal recessive AD/AR N/A N/A Musculoskeletal; Neurologic General Medical treatment (eg, with Cyclosporin A) may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 963533; 11381124; 12297580; 15563506; 15689448; 16075202; 15955946; 17886299; 18852439; 19564581; 20106987; 20302629; 20301676; 21280092; 23138527 COL6A3 2213 1293 Ullrich congenital muscular dystrophy 1; Bethlem myopathy 1; Dystonia 27 AD/AR N/A N/A Musculoskeletal General Medical treatment (eg, with Cyclosporin A) may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 963533; 11992252; 15563506; 15689448; 16141002; 17886299; 18362356; 18366090; 19564581; 20301676; 20976770; 21496625; 21943391; 22526018; 26004199 COL7A1 2214 1294 Epidermolysis bullosa dystrophica, autosomal dominant; Epidermolysis bullosa dystrophica, autosomal recessive; Epidermolysis bullosa dystrophica inversia; Epidermolysis bullosa pruriginosa; Nail disorder, nonsyndromic congenital, 8; Epidermolysis bullosa dystrophica, Bart type; Epidermolysis bullosa, pretibial; Transient bullous dermolysis of the newborn AD/AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1347297; 1680286; 8513326; 8345225; 8245264; 8170945; 8037207; 8541842; 7577595; 8644729; 9406826; 9347800; 9182828; 9856844; 9892921; 10583163; 10383749; 10469344; 12485454; 11874498; 11843659; 12787275; 16225626; 16965329; 17434045; 16971478; 20574443; 20920254; 21113014; 21182502; 21196708; 21352278; 21382783; 21574979; 21629976; 21849769; 21967228; 22058051; 22266148; 22515571; 22854212; 22909362; 22974128; 23013315 COL8A2 2216 1296 Corneal dystrophy polymorphous posterior, 2; Corneal dystrophy, Fuchs endothelial, 1 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 399801; 11689488; 15914606; 18024822; 18464802 COL9A1 2217 1297 Stickler syndrome, type IV AR Pediatric Allelic with Epiphyseal dysplasia, multiple, 6 (AD) Audiologic/Otolaryngologic; Craniofacial;Musculoskeletal; Ophthalmologic Audiologic/Otolaryngologic; Ophthalmologic Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated 11565064; 16909383; 20301479 COL9A2 2218 1298 Stickler syndrome, Type V AR Pediatric Allelic with Epiphyseal dysplasia, multiple, 2 (AD) Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic Audiologic/Otolaryngologic; Ophthalmologic Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated 3238439; 8528240; 12244547; 15633184; 20358595; 21671392; 20301479 COL9A3 2219 1299 Epiphyseal dysplasia, multiple, 3 AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10090888; 10655510; 15551337; 20301302 COLEC10 2220 10584 3MC syndrome 3 AR N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28301481 COLEC11 17213 78989 3MC syndrome 2 AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal Audiologic/Otolaryngologic The condition can involve multiple congenital anomalies Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 2569826; 8933348; 21258343 COLGALT1 26182 79709 Brain small vessel disease 3 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30412317 COLQ 2226 8292 Myasthenic syndrome, congenital, 5 AR Pediatric Musculoskeletal; Neurologic Musculoskeletal; Neurologic; Pharmacogenomic Endplate acetylcholinesterase deficiency has been reported as nonresponsive to treatment Most individuals with CMS benefit from AChE inhibitors and/or potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; Some individuals with Slow-channel congenital myasthenic syndrome,are treated with quinidine, which has some major side effects and may be detrimental in individuals with AChR deficiency; Additional neurologic monitoring in pregnancy may be beneficial 9758617; 9689136; 10441569; 11865139; 23108489 COMP 2227 1311 Epiphyseal dysplasia, multiple, 1; Pseudoachondroplasia AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13633894; 3314506; 7907311; 7670471; 7670472; 8725795; 9021009; 9188668; 9887340; 11968079; 14684695; 15266613; 15551305; 17579668; 20301302; 20830670; 21599986; 21644213; 21922596; 21965141; 22006726 COMT 2228 1312 Medication response, association with AD Pediatric General Pharmacogenomic Variants may involve clinically relevant drug metabolism 12716966; 15927391; 16876132; 17522626; 17644310; 18214865; 19462300; 19858760; 20053459; 20071037; 20216107; 20591499; 20877297; 21280081; 21788083; 22417933; 22483292 COPA 2230 1314 Autoimmune interstitial lung, joint, and kidney disease AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may manifest with multisystemic autoimmune conditions, and medical management with immunosuppressive therapy has been described such that early awareness may allow prompt treatment 25894502 COPB1 2231 1315 Baralle-Macken syndrome AD Pediatric Allergy/Immunology/Infectious; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Allergy/Immunology/Infectious Among other features, individuals have been described with immunodeficiency, and awareness may allow preventive measures and early and aggressive treatment of infections 33632302 COPB2 2232 9276 Microcephaly 19, primary, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29036432 COQ2 25223 27235 Coenzyme Q10 deficiency, primary, 1 AR Pediatric Biochemical; Musculoskeletal; Neurologic; Renal Biochemical A heterogenous group of disorders has been described, but the molecular etiologies of some are unclear; Variants may contribute to Multiple system atrophy, susceptibility to 1 (AR) Treatment with coenzyme Q10 has been described as beneficial 16116126; 17855635; 17374725; 17332895; 17420317; 23758206; 24988567; 24988570 COQ4 19693 51117 Coenzyme Q10 deficiency 7 AR Pediatric Biochemical; Cardiovascular; Neurologic Biochemical Treatment with coenzyme Q10 has been described as possibly beneficial 22368301; 25658047; 33704555 COQ5 28722 84274 Coenzyme Q10 deficiency, primary, 1 AR Pediatric Biochemical; Neurologic Biochemical Treatment with coenzyme Q10 has been described as beneficial 29044765 COQ6 20233 51004 Coenzyme Q10 deficiency, primary 6 AR Pediatric Biochemical; Musculoskeletal; Neurologic; Renal Biochemical Some patients have been reported as showing a favorable response to oral Coenzyme Q supplementation 21540551 COQ7 2244 10229 Coenzyme Q10 deficiency, primary 8 AR Pediatric Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Renal Biochemical Treatment with coenzyme Q10 has been described as possibly beneficial 26084283 COQ8A 16812 56997 Coenzyme Q10 deficiency, primary 4 AR Pediatric Biochemical; Neurologic Biochemical Treatment with coenzyme Q10 may have some benefit in some individuals, though some features may not be affected, and some invidiuals may not derive benefit 12682339; 15326254; 18319074; 18319072; 20580948; 22036850; 22231380; 32337771 COQ8B 19041 79934 Nephrotic syndrome, type 9 AR Pediatric Renal Biochemical; Renal The condition manifests as steroid-resistant nephrotic syndrome, with focal segmental glomerulosclerosis, and treatment with coenzyme Q10 has been described as beneficial 24270420 COQ9 25302 57017 Coenzyme Q10 deficiency 5 AR Pediatric Biochemical; Musculoskeletal; Neurologic; Renal Biochemical Treatment with coenzyme Q10 can be beneficial 11562630; 19375058 CORIN 19012 10699 Preeclampsia/eclampsia 5 AD Pediatric Obstetric Obstetric Individuals may be at high risk for pregnancy complications such as preeclampsia/eclampsia, and thus preconception planning, surveillance during pregnancy (eg, including related to proteinuria, hypertension, liver function, and hematologic parameters), as well as delivery planning may be beneficial in order to decrease associated morbidity and mortality 22437503 CORO1A 2252 11151 Immunodeficiency 8 AR Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic The condition can involve recurrent infections, and awareness may allow preventive measures, and early and aggressive treatment of infections; Individuals have been described with oncologic sequelae of infections (such as EBV-related lymphoproliferative disorders) and awareness may allow prompt diagnosis and management; BMT has been described 19097825; 23522482; 25073507 COX10 2260 1352 Mitochondrial complex IV deficiency, nuclear type 3 AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Hematologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10767350 COX14 28216 84987 Mitochondrial complex IV deficiency, nuclear type 10 AR N/A N/A Cardiovascular; Biochemical; Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22243966 COX15 2263 1355 Mitochondrial complex IV deficiency, nuclear type 6 AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2175025; 12474143; 15235026; 15863660; 21412973 COX16 20213 51241 Mitochondrial complex IV deficiency, nuclear type 22 AR N/A N/A Cardiovascular; Biochemical; Gastrointestinal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33169484 COX20 26970 116228 Mitochondrial complex IV deficiency, nuclear type 11 AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23125284; 24202787 COX4I1 2265 1327 Mitochondrial complex IV deficiency, nuclear type 16 AR Pediatric Biochemical; Craniofacial; Musculoskeletal; Neurologic Biochemical Treatment with coenzyme Q has been described as resulting in mild clinical improvement 28766551; 31290619 COX4I2 16232 84701 Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis AR Pediatric Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic Gastrointestinal Pancreatic enzyme supplementation has been reported to improve psychomotor development, as well as direct sequelae such as steatorrhea 19268275 COX5A 2267 9377 Mitochondrial complex IV deficiency, nuclear type 20 AR Pediatric Biochemical; Cardiovascular; Neurologic General Among other findings, the condition may involve pulmonary artery hypertension, and awareness may allow early management 28247525 COX6A1 2277 1337 Charcot-Marie-Tooth disease, recessive intermediate D AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25152455 COX6A2 2279 1339 Mitochondrial complex IV deficiency, nuclear type 18 AR N/A N/A Biochemical; Cardiovascular; Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31155743 COX6B1 2280 1340 Mitochondrial complex IV deficiency, nuclear type 7 AR N/A N/A Biochemical; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18499082 COX7B 2291 1349 Linear skin defects with multiple congenital anomalies 2 XL N/A N/A Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9747372; 23122588 COX8A 2294 1351 Mitochondrial complex IV deficiency, nuclear type 15 AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26685157 CP 2295 1356 Aceruloplasminemia AR Pediatric Biochemical; Endocrine; Gastrointestinal; Neurologic; Ophthalmologic Biochemical In Aceruloplasminemia, medical management can be beneficial (eg, with iron chelating agents to decrease serum ferritin, brain and liver iron stores, and prevent progression of neurologic signs/symptoms; Combined IV desferrioxamine and fresh-frozen plasma can decrease liver iron content; repetitive FFP treatment can improve neurologic manifestations; antioxidants and oral zinc and deferasirox may prevent tissue damage to the liver and pancreas 3574673; 1458725; 7820540; 7539672; 9066364; 20301666 CPA6 17245 57094 Febrile seizures, familial, 11; Epilepsy, familial temporal lobe, 5 AR N/A N/A Neurologic General As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21922598; 23105115 CPAMD8 23228 27151 Anterior segement dysgenesis 8 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27839872 CPE 2303 1363 Intellectual developmental disorder and hypogonadotropic hypogonadism AR Pediatric Endocrine; Neurologic Endocrine Among other findings, individuals may manifest with hypothyroidism and hypogonadotropic hypogonadism, and awareness may allow medical treatment of these endocrine diosrders 26120850; 32936766 CPLANE1 25801 65250 Joubert syndrome 17; Orofaciodigital syndrome VI AR N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General The condition may involve multi-systemic manifestations, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5816874; 20301500; 22425360; 23169490; 24178751 CPLX1 2309 10815 Developmental and epileptic encephalopathy 63 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26539891; 28422131 CPN1 2312 1369 Carboxypeptidase N deficiency AR N/A N/A Allergy/Immunology/Infectious General Heterozygotes may demonstrate milder manifestations The consequences of the condition are unclear, though genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7437116; 12560874; 18068674 CPOX 2321 1371 Coproporphyria; Harderoporphyria AD/AR Pediatric Gastrointestinal; Hematologic; Neurologic Hematologic; Pharmacogenomic In Coprophyria, attacks may be precipitated by a variety of agents (eg, fasting, as well as specific pharmaceutical agents, including oral contraceptives), which should be avoided; IV therapy (with heme arginate) has been described as effective; In heterozygotes, specific considerations are important in surgery (eg, use of IV glucose perioperatively) and related to agent selection for anesthesia induction; Liver transplanation has been described; In Harderoporphyria, individuals may suffer from neonatal hemolytic anemia, which may necessitate RBC transfusions 14378650; 5838412; 4163920; 4393048; 74745; 6886003; 6502649; 6143037; 8012360; 8286403; 7757079; 11309681; 12227458; 12181641; 16151909; 16159891; 21103937; 23236641 CPS1 2323 1373 Carbamoylphosphate synthetase I deficiency AR Pediatric Biochemical; Neurologic Biochemical; Pharmacogenomic Specific urgent and long-term medical management (eg, dietary measures, arginine, sodium benzoate, sodium phenylbutyrate), as well as measures such as dialysis when necessary, may be beneficial to reduce morbidity and mortality; Avoidance of certain agents (eg, valproate), as well as special considerations in situations such as peregnancy, are warranted due to potential adverse events 5356974; 5471650; 4111816; 4811018; 7078580; 6427608; 3759432; 3792387; 1414247; 8486760; 8273985; 9711878; 21120950; 16708072; 17310273; 19793055; 21120950; 22173106; 25135652; 25410056 CPSF1 2324 29894 Myopia 27 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30689892 CPT1A 2328 1374 Carnitine palmitoyltransferase deficiency I AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Renal Biochemical; Pharmacogenomic Dietary management, including avoidance of fasting and prompt treatment of hypoglycemia, can prevent and treat metabolic decompensation, and can prevent neurologic damage; Surveillance for hepatic dysfunction may be beneficial, and potentially hepatoxic agents should be avoided 7014807; 3211616; 1598098; 1403388; 9691089; 10625081; 11286380; 11350182; 12189492; 15110323; 20301700; 20696606; 21962599 CPT1C 18540 126129 Spastic paraplegia 73, autosomal dominant AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25751282 CPT2 2330 1376 Carnitine palmitoyltransferase II deficiency AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Renal Biochemical; Musculoskeletal; Pharmacogenomic; Renal There are diverse presentations, including a lethal neonatal, severe infantile hepatocardiomuscular, and myopathic forms, and optimal treatment may vary according to the phenotype; Severe, life-threatening rhabdomyolytic episodes can be precipitated by illness, prolonged exercise, dehydration, or fasting, and medical therapy (eg, with fibrates), along with avoidance of these precipitating factors (and interventions such as IV glucose in the instance of acute episodes) can be beneficial; Dietary measures (high-carbohydrate/low-fat diet) and medications (eg, carnitine) can be beneficial; Certain medications should be avoided, including valproate, general anesthesia, ibuprofen, and high-dose diazepam 5416202; 123038; 187736; 736528; 272487; 2748260; 2712755; 1999498; 1940982; 1528846; 8358442; 8201482; 8651281; 8786066; 8682496; 11389301; 11477613; 11595519; 12410208; 12673791; 15363638; 15642848; 15622536; 18471680; 18550408; 18925671; 19228633; 19335026; 20661589; 20301431; 20505667; 20543534; 20810031; 21641254; 21913903; 23184072; 23326270 CR1 2334 1378 Blood group, Knops system BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 11724985 CR2 2336 1380 Common variable immune deficiency, 7 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 22035880 CRADD 2340 8738 Mental retardation, autosomal recessive 34, with variant lissencephaly AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22279524; 27773430 CRAT 2342 1384 Neurodegeneration with brain iron accumulation 8 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29395073 CRB1 2343 23418 Leber congenital amaurosis 8; Retinitis pigmentosa 12, autosomal recessive; Pigmented paravenous chorioretinal atrophy AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 434087; 6614113; 3778279; 2801856; 10508521; 11389483; 15024725; 15623792; 16543197; 16564825; 19140180; 20006823; 21484995; 22065545; 22277662; 23077403; 23379534 CRB2 18688 286204 Focal segmental glomerulosclerosis 9; Ventriculomegaly with cystic kidney disease AR Pediatric Neurologic; Renal Renal The condition can involve steroid-resistant nephrotic syndrome, and early diagnosis may allow early and more specific management 25557779; 25557780 CRBN 30185 51185 Mental retardation, autosomal recessive 2 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10932263; 15557513; 17036314; 17380424 CREB3L1 18856 90993 Osteogenesis imperfecta, type XVI AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24079343; 30657919 CREB3L3 18855 84699 Hypertriglyceridemia 2 AD Pediatric Cardiovascular Cardiovascular The condition can involve hypertriglyceridemia, and management via diet and omega-3 fatty acid therapy has been described as beneficial 26427795; 29954705 CREBBP 2348 1387 Rubinstein-Taybi syndrome; Menke-Hennekam syndrome 1 AD Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic ; Oncologic; Ophthalmologic Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Hematologic; Cardiovascular; Oncologic; Ophthalmologic Rubinstein-Taybi syndrome can include a risk of frequent infections (especially respiratory infections), and prophylaxis and early and aggressive treatment of infections may be beneficial; There may be increased risk of malignancy, and awareness may allow early detection and treatment of oncologic processes; Due to the possibility of cardiovascular anomalies (including arrhythmia), surveillance may be beneficial; Surveillance for certain types of ophthalmologic manifestations (eg, glaucoma) may be beneficial in order to allow prompt treatment; Menke-Hennekam syndrome can include frequent infections, and prophylaxis and early and aggressive treatment of infections may be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 13983033; 7137629; 7747773; 7630403; 10573006; 15706485; 16913274; 18792986; 19852432; 20301699; 20717166; 20949605; 21085895; 21189944; 22426292; 23432975; 27311832; 29460469; 30737887 CRELD1 14630 78987 Atrioventricular septal defect, partial, with or without heterotaxy AD N/A N/A Cardiovascular; Gastrointestinal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12632326; 15857420; 21080147; 22740159 CRIPT 14312 9419 Short stature with microcephaly and distinctive facies AR N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24389050; 27250922 CRLF1 2364 9244 Crisponi/Cold-induced sweating syndrome, type 1 AR Pediatric Musculoskeletal; Neurologic Neurologic In the neonatal/early childhood period, the condition can be lethal unless advanced care is instituted; Later, it has been described that cold-induced sweating was alleviated by medical treatment (eg, with clonidine) 8723066; 12509788; 17436252; 17436251; 18837055; 19012339; 20186812; 20400119; 21326283; 21370513; 23026229 CRPPA 37276 729920 Muscular dystrophy-dystroglycanopathy (congenital, with brain and eye anomalies), type A, 7; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7 AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7604843; 9492098; 22522421; 22522420; 23390185 CRTAP 2379 10491 Osteogenesis imperfecta, type VII AR N/A N/A Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12110406; 17192541; 17055431; 19862557; 21955071; 21964860; 23613367; 25604815 CRX 2383 1406 Leber congenital amaurosis 7; Cone-rod dystrophy 2 AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9390563; 9390562; 9537410; 9931337; 12208271; 15531334; 20301475; 20301590; 20513135; 22960069 CRY1 2384 1407 Delayed sleep phase syndrome, susceptibility to AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28388406 CRYAA 2388 1409 Cataract 9, multiple types AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9467006; 11006246; 14512969; 16564818; 17296897; 18302245; 20465443; 20606865; 21866213; 22065922; 22216983; 23255486 CRYAB 2389 1410 Myopathy, myofibrillar, 2; Cardiomyopathy, dilated, 1II AD Pediatric Allelic with Cataract 16, multiple types (AD); Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related (AR) Cardiovascular; Musculoskeletal; Ophthalmologic Cardiovascular Individuals have been described with a combination of cardiovascular, musculoskeletal, and ophthalmologic manifestations, as well as apparently isolated findings affecting each of these organ systems Individuals with Myopathy, myofibrillar, 2 typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD); Cardiac transplantation may be necessary in individuals with severe forms of cardiomyopathy; Individuals with Cardiomyopathy, dilated, 1II may present with arrhythmias, including sequelae such as sudden cardiac death, and surveillance (eg, with electrocardiogram and echocardiogram) may allow early management as described for other CRYAB-related cardiac manifestations 570292; 8000975; 9731540; 11577372; 14681890; 16483541; 16793013; 20301672; 21337604; 21920752; 23197161; 23590293 CRYBA1 2394 1411 Cataract 10, multiple types AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7573044; 9788845; 17653060; 20142846; 21686330; 21850182; 21866213; 22665976 CRYBA2 2395 1412 Cataract 42 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23508780 CRYBA4 2396 1413 Cataract 23 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16960806; 20577656 CRYBB1 2397 1414 Cataract 17, multiple types AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12360425; 17460281; 21972112 CRYBB2 2398 1415 Cataract 3, multiple types AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2240043; 8812489; 9158139; 10634616; 11424921; 17234267; 18617901; 19649175; 21031021; 21245961; 22312185; 22846113 CRYBB3 2400 1417 Cataract 22, multiple types AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15914629; 27326458; 28418495; 23508780 CRYGB 2409 1419 Cataract 39, multiple types AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23288985 CRYGC 2410 1420 Cataract 2, multiple types AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8190472; 10521291; 10914683; 12011157; 18587492; 18618005; 19204787; 22052681; 22876111 CRYGD 2411 1421 Cataract 4, multiple types AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8733140; 10521291; 9927684; 10915766; 12567263; 12011157; 12676897; 17564961; 18587492; 19262743; 19633732; 19668596; 20508808; 21031598; 21552497; 21866214; 22219628; 22669729 CRYGS 2417 1427 Cataract 20, multiple types AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16141006; 18587492; 19262743 CRYM 2418 1428 Deafness, autosomal dominant 40 AD Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic As some patients have been described with prelingual hearing loss, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12471561 CSF1R 2433 1436 Leukoencephalopathy, diffuse hereditary, with spheroids; Brain abnormalities, neurodegeneration, and dysosteosclerosis AD/AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16523341; 19153373; 22197934; 22843259; 23698128; 30982608; 30982609 CSF2RA 2435 1438 Surfactant metabolism dysfunction, pulmonary, 4 XL Pediatric Pulmonary Pulmonary The condition manifests with childhood-onset respiratory insufficiency due to pulmonary alveolar proteinosis , and treatment with whole-lung lavage has been reported as beneficial; It has additionally been reported that diagnosis has important therapeutic implications, as BMT/HSCT can be effective 18955567; 18955570; 20622029 CSF2RB 2436 1439 Surfactant metabolism dysfunction, pulmonary, 5 AR Pediatric Pulmonary Pulmonary The condition typically manifests with childhood-onset respiratory insufficiency (though adult-onset disease has also been reported) due to pulmonary alveolar proteinosis, and whole-lung lavage may be beneficial; It has been reported that diagnosis has important therapeutic implications, as BMT/HSCT can be effective 9410898; 21075760 CSF3R 2439 1441 Neutropenia, severe congenital, 7, autosomal recessive AR Pediatric Allelic with Neutrophilia, hereditary (AD) Allergy/Immunology/Infectious; Hematologic Allergy/Immunology/Infectious One individual with Neutrophilia has been described as developing a myelodysplastic syndrome with refractory anemia Individuals have been described with early-onset severe and recurrent infections, and prophylactic measures (eg, GM-CSF, but not G-CSF has been reported as beneficial) as well as early and aggressive treatment of infections may be beneficial 4825608; 19620628; 24753537; 26324699 CSGALNACT1 24290 55790 Skeletal dysplasia, mild, with joint laxity and advanced bone age AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27599773; 31325655; 31705726 CSNK1D 2452 1453 Advanced sleep phase syndrome, familial, 2 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15800623; 23636092 CSNK2A1 2457 1457 Okur-Chung neurodevelopmental syndrome AD Pediatric Allergy/Immunology/Infectious; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Among other findings, individuals have been described with hypogammaglobulinemia and mild IgA or IgG deficiency and awareness may allow surveillance and management related to potential infectious sequelae 27048600; 28725024; 29240241; 29383814; 29619237 CSNK2B 2460 1460 Poirier-Bienvenu neurodevelopmental syndrome AD N/A N/A Craniofacial; Dental; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28585349; 28762608; 30655572; 31784560 CSPP1 26193 79848 Joubert syndrome 21 AR N/A N/A Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Mild sensorineural hearing loss has been described in several individuals Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24360803; 24360807; 24360808 CSRP3 2472 8048 Cardiomyopathy, familial hypertrophic 12; Cardiomyopathy, dilated, 1M AD Pediatric Cardiovascular; Musculoskeletal Cardiovascular There is a wide range of age at presentation Surveillance for manifestations (including with electrocardiogram and echocardiogram), including in asymptomatic individuals, is recommended; For individuals with cardiomyopathy, treatment such as medical therapy, pacemakers, and ICD can decrease morbidity and mortality, and early recognition and treatment can improve outcomes, though some individuals with progressive/refractory disease may require cardiac transplantation 12507422; 14567970; 12642359; 18505755; 20087448; 22429680 CST3 2475 1471 Cerebral amyloid angiopathy, CST3 related AD N/A N/A Cardiovascular; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4655034; 3495457; 2900981; 11760381; 16612982; 18566660 CST6 2478 1474 Ectodermal dysplasia 15, hypohydrotic/hair type AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30425301 CSTA 2481 1475 Peeling skin syndrome 4 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21944047; 25400170 CSTB 2482 1476 Myoclonic epilepsy of Unverricht and Lundborg AR N/A N/A Neurologic General Some medications (reports include valproate, N-acetylcysteine, levetiracetam) can result in marked improvement, but phenytoin can worsen neurologic manifestations, and can even increase cerebellar degeneration; Other medications (eg, carbamazepine, oxcarbazepine, tiagabine, vigabatrin, gabapentin, pregabalin) can worsen myoclonus/myoclonic seizures Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6137660; 8596935; 9012407; 9054946; 9126745; 9090386; 9527146; 9529356; 9814834; 9932979; 12427904; 12707458; 15508934; 15778103; 18325013; 20301321; 20593193 CTBP1 2494 1487 Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome AD N/A N/A Dental; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27094857 CTC1 26169 80169 Cerebroretinal microangiopathy with calcifications and cysts 1 AR N/A N/A Cardiovascular; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3402627; 8628470; 15002047; 15079028; 16943371; 18076099; 21523908; 22267198; 22387016 CTCF 13723 10664 Mental retardation, autosomal dominant, 21 AD N/A N/A Neurologic General One described individual had multiple congenital anomalies in addition to neurologic manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23746550 CTDP1 2498 9150 Congenital cataracts, facial dysmorphism, and neuropathy AR Pediatric Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal Endocrine; Pharmacogenomic; Renal Individuals may have hypogonadotropic hypogonadism, and medical management (hormone replacement) may be beneficial to prevent osteoporosis; In the instance of anesthesia, monitoring is indicated, (eg, for severe complications such as stridor, pulmonary edema, malignant hyperthermia, and seizures); Individuals may suffer severe rhabdomyolysis related to viral infections, and awareness may allow rapid management 10439962; 10360766; 10442556; 14517542; 16194727; 16939648; 20301787; 21824574 CTH 2501 1491 Cystathioninuria AR N/A N/A Biochemical General It is unclear if the condition causes clinical manifestations other than biochemical abnormalities, and medical management (eg, with pyridoxine) may improve the biochemical parameters, though it is unclear if possibly coincident clinical findings are also affected Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14399948; 5637757; 12574942; 20584029 CTHRC1 18831 115908 Barrett esophagus/Esophageal adenocarcinoma AD Adult Gastrointestinal; Oncologic Gastrointestinal; Oncologic Awareness of disease risk may allow surveillance, preventive measures (eg, related to Barrett esophagus) and early treatment of malignancy, which may reduce morbidity and mortality 21791690 CTLA4 2505 1493 Autoimmune lymphoproliferative syndrome, type V AD Pediatric Allergy/Immunology/Infectious; Hematologic; Oncologic; Renal Allergy/Immunology/Infectious; Oncologic Medical treatment (with immunosuppression) has been described as beneficial; The condition may involve frequent infections, and awareness may allow preventive measures and early and aggressive treatment of infections 25213377; 25329329 CTNNA1 2509 1495 Hereditary diffuse gastric cancer, familial AD Adult Allelic with Macular dystrophy, patterned 2 (AD) Oncologic; Ophthalmologic Oncologic Awareness of disease risk may allow surveillance for and early treatment of neoplastic disease, which may reduce morbidity and mortality 5442145; 23208944; 26182300; 26691986; 29330337; 30515673 CTNNA2 2510 1496 Cortical dysplasia, complex, with other brain malformations, 9 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30013181 CTNNA3 2511 29119 Arrhythmogenic right ventricular dysplasia, familial, 13 AD Pediatric Cardiovascular Cardiovascular Individuals have been described as presenting with arrhthymias and echocardiographic findings including right ventricular dilatation and dyskinesia, and awareness can allow surveillance (eg, with echocardiogram, electrocardiogram) and preventive measures and early treatment (eg ,with ICD) 23136403 CTNNB1 2514 1499 Exudative vitreoretinopathy 7; Neurodevelopmental disorder with spastic diplegia and visual defect (Mental retardation, autosomal dominant 19) AD N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23033978; 24614104; 24668549; 25326669; 27915094; 28514307; 28575650 CTNND1 2515 1500 Blepharocheilodontic syndrome 2 AD N/A N/A Craniofacial; Dermatologic; Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28301459 CTNS 2518 1497 Cystinosis AR Pediatric Biochemical; Endocrine; Musculoskeletal; Ophthalmologic; Renal Biochemical; Endocrine; Ophthalmologic; Renal Cystine-depleting agents (cysteamine) instituted at an early age can be beneficial related to manifestations affecting multiple organ systems, perhaps including cognitive development, as well as renal manifestations (renal tubular Fanconi syndrome and glomerular damage), though renal transplantation may be necessary; Surveillance for renal manifestations and related sequelae can allow early detection and management of disease with (in addition to cystine-depleting agents), replacement of renal losses; Dietary management (eg, ensuring sufficient caloric intake, and with vitamin D and phosphate supplementation) can be beneficial related to potential failure to thrive and hypophosphatemic rickets; Cysteamine eyedrops can be beneficial related to ophthalmologic sequelae; Surveillance for endocrine manifestations (eg, hypothyroidism, or hypogonadism in males) can allow early detection and medical management, including potential use of growth hormone in order to optimize height in some individuals 6038997; 4914142; 5443335; 406375; 333912; 7112129; 3307383; 3335962; 3550461; 3674101; 3821824; 3335962; 3185663; 3292915; 381441; 2230837; 552398; 8455682; 8172256; 7593434; 9537412; 10556299; 10417278; 10444339; 10625078; 11001803; 10673275; 12110740; 12442267; 16603246; 17643777; 19863563; 20301574; 20803298; 20814825; 21305353; 21784456; 21868618; 21371554; 21900880; 22903658; 23001048; 23462307; 23538568; 25165189 CTPS1 2519 1503 Immunodeficiency 24 AR Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic Individuals are susceptible to frequent and severe viral and bacterial infections (as well as sequelae such as EBV-related lymphoma), and and antiinfectious prophylaxis and early and aggressive treatment of infections, as well as awareness of potential oncologic sequelae, may be beneficial; HSCT has been described 24870241 CTSA 9251 5476 Galactosialidosis AR Pediatric Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal Biochemical Cardiac manifestations (eg, valvular anomalies and insufficiency) can be severe, and surveillance (eg, with echocardiogram) may allow early detection of sequalae and treatment; Cytopenias have been described; Renal transplanation has been described as beneficial 4999185; 3149149; 2148053; 8514852; 7759227; 8725271; 8968752; 9762607; 10944848; 18937050 CTSB 2527 1508 Keratolytic winter erythema AD N/A N/A Dermatologic General Reported variants involved duplications upstream of the gene (and which disrupted CTSB gene function) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28457472 CTSC 2528 1075 Haim-Munk syndrome; Papillon-Lefevre syndrome; Periodontitis 1, juvenile AR Pediatric Allergy/Immunology/Infectious; Dental; Dermatologic; Musculoskeletal Allergy/Immunology/Infectious Early diagnosis to allow control of oral infections may preserve dentition 14244097; 14252683; 162525; 2943312; 2965550; 7623262; 9085215; 10593994; 10581027; 11106356; 10662807; 12509601; 12637913; 14974080; 15606524; 18945301; 19816003; 20359428; 21393975 CTSD 2529 1509 Ceroid lipofuscinosis, neuronal, 10 AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16670177; 16685649; 25298308 CTSF 2531 8722 Neuronal ceroid lipofuscinosis 13 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20301601; 23297359 CTSK 2536 1513 Pycnodysostosis AR N/A N/A Biochemical; Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14041831; 14470123; 1611757; 8703060; 9529353; 10074491; 15070910; 17397052; 19674475; 20305575; 21099701 CTU2 28005 348180 Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome AR N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26633546; 27480277 CUBN 2548 8029 Immerslund-Grasbeck syndrome 1 AR Pediatric Gastrointestinal; Hematologic; Renal Gastrointestinal Allelic with Proteinuria, chronic benign (AR) Early diagnosis is beneficial, as early detection may allow life-long medical treatment with parenteral hydroxocobalamin, which can ameliorate morbidity and mortality 15024727; 22854512; 22929189; 31613795 CUL3 2553 8452 Pseudohypoaldosteronism, type IIE AD Pediatric Allelic with Neurodevelopmental disorder with or without autism or seizures (AD) Neurologic; Renal Renal Treatment (eg, correction of physiologic abnormalities by thiazide diuretics) can be effective 22266938; 31696658; 31780330; 32341456; 33097317 CUL4B 2555 8450 Mental retardation, X-linked, syndromic 15 (Cabezas type) XL N/A N/A Craniofacial; Endocrine; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8135271; 10978355; 11562927; 17236139; 17273978; 19377476; 20002452; 20014135; 24898194 CUL7 21024 9820 Three M syndrome 1 AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16142236; 17675530; 19225462; 21166787; 22624670; 22974575 CUX1 2557 1523 Global developmental delay with or without impaired intellectual development AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30014507 CUX2 19347 23316 Developmental and epileptic encephalopathy 67 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29630738; 29795476 CWC27 10664 10283 Retinitis pigmentosa with or without skeletal anomalies AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28285769 CWF19L1 25613 55280 Spinocerebellar ataxia, autosomal recessive 17 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15981765; 25361784 CXCR4 2561 7852 Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome AD Pediatric Allergy/Immunology/Infectious; Dermatologic; Hematologic Allergy/Immunology/Infectious; Hematologic Because of HPV infections, the condition may include oncologic manifestations Individuals can be susceptible to a number of types of infections as well as hematologic sequelae, and prophylaxis and medical management (eg, including HPV vaccine, GCSF, CXCR4 antagonists) and early and aggressive treatment of infections can be beneficial 889707; 2239986; 10767001; 12692554; 25662009; 30625055 CYB5A 2570 1528 Methemoglobinemia and ambiguous genitalia AR Pediatric Endocrine; Hematologic; Oncologic; Genitourinary Endocrine; Oncologic; Genitourinary Hormonal treatment (eg, with estrogen or testosterone) may be beneficial related to sexual characteristics; Due to risk of gonadal tumors, surgical removal may be indicated 3951505; 8168836; 22170710 CYB5R3 2873 1727 Methemoglobinemia due to methemoglobin reductase deficiency AR Pediatric Biochemical; Hematologic; Neurologic Biochemical; Pharmacogenomic Some forms of disease are responsive to medical therapy (eg, with ascorbic acid), though neurological manifestations in severe forms have not been described as being impacted by this type of management; In treatment with certain medications (eg, Dapsone), genotyping may assist in the prevention and/or early treatment of adverse reactions 21011935; 18861684; 1207738; 4063522; 3539237; 1707593; 8427971; 7668255; 7718898; 9266404; 9695975; 10874300; 12803131; 15921385; 15390276; 17964195; 18202104; 18343696; 18820099; 18318771; 19579085; 19997042; 21328435; 22627575; 22658170; 22797852 CYBA 2577 1535 Granulomatous disease, chronic, autosomal recessive, 4 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Surveillance for infections and infectious complications is indicated, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation 4384563; 2770793; 3368442; 2713485; 2243141; 1415254; 11060536; 12073015; 18422995; 10759707; 20407811; 22336310; 22562447; 22876374; 22924696; 23910690 CYBB 2578 1536 Granulomatous disease, chronic, X-linked; Immunodeficiency 34 XL Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious In Immunodeficiency 34, BCG vacine should be avoided, and recognition may allow prompt diagnosis and treatment of infectious manifestations; In Chronic granulomatous disease, X-linked, surveillance for infections and infectious complications is indicated, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation 13430573; 13636694; 14258653; 4163887; 6021213; 4191616; 7273485; 6851217; 3011845; 2556453; 1710153; 8807090; 9454688; 9888386; 10914676; 11060536; 11259721; 11138621; 12802027; 17544093; 18762975; 21278736; 22236433; 22876374; 22924737; 23193493; 23826567; 23827747; 23859418; 23910690 CYBC1 28672 79415 Granulomatous disease, chronic, autosomal recessive, 5 AR Pediatric Allergy/Immunology/Infectious; Musculoskeletal Allergy/Immunology/Infectious Surveillance for infections and infectious complications is indicated, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation 28600779; 30312704; 30361506 CYC1 2579 1537 Mitochondrial complex III deficiency, nuclear, type 6 AR Pediatric Biochemical Biochemical Individuals may present with episodes of acute metabolic decompensation, including hyperlactatemia, hyperammonemia, ketoacidosis and glucose instability, and awareness may allow rapid treatment, including with IV rehydration (and insulin therapy as required), as well as other biochemical interventions (eg, arginine and sodium benzoate) 23910460 CYCS 19986 54205 Thrombocytopenia 4 AD N/A N/A Hematologic General Reported clinical findings related to thrombocytopenia were absent or mild; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18345000; 22102269; 24326104; 30051457 CYFIP2 13760 26999 Developmental and epileptic encephalopathy 65 AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29534297 CYLD 2584 1540 Allelic with Frontotemporal dementia and/or amyotrophic lateral sclerosis8 (AD) AD Pediatric Dermatologic; Neurologic; Oncologic Dermatologic; Oncologic The condition can include a number of types of cancerous lesions for which surveillance/treatment (including surgical management) may be beneficial; In familial trichoepithelioma, skin lesions can degenerate into basal cell carcinoma; In Cylindromatosis, familial, childhood tumors have been reported, and neoplasms may undergo malignant transformation; Individuals are at risk of salivary/parotid adenocarcinoma 8436650; 7684205; 10835629; 11703297; 12190880; 14632188; 12950348; 15854031; 16307661; 16922728; 18234730; 19076795; 19807742; 19917957; 20151946; 20972631; 21712687; 22049921; 22588548; 22689134; 22296260; 22882113; 23249834; 23260808; 23567228; 23694822; 32185393; 32666117 CYP11A1 2590 1583 Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete AD/AR Pediatric Endocrine; Oncologic; Genitourinary Endocrine; Oncologic; Genitourinary Presentation of classic enzymatic deficiency involves adrenal failure and salt wasting in infancy, which can be treatable; Nonclassic forms may present later with some retained adrenal function and abnormal sexual development; Surgical interventions may decrease the risk of gonadal tumors 11502818; 12161514; 15507506; 16705068; 18182448; 21159840 CYP11B1 2591 1584 Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency; Hyperaldosteronism, familial, type I AD/AR Pediatric Endocrine; Oncologic; Genitourinary Endocrine; Oncologic; Genitourinary Glucocorticoid-remediable aldosteronism involves a fusion gene (with CYP11B2) In Adrenal hyperplasia, treatment of manifestations such as hypertension (fatal vascular accidents have been reported in individuals with relatively mild virilization) and hypokalemia, as well as genitourinary anomalies, can be beneficial; Screening for oncologic complications (eg, testicular adrenal rest tumors) can allow early detection and treatment; In Hyperaldosteronism, familial, type I, medical treatment (eg, with glucocorticoids) can be beneficial 13345203; 7355668; 7026592; 6268979; 7049883; 3875277; 2022736; 1430088; 17172090; 1731223; 1472060; 1554023; 7670248; 7550315; 8825044; 8768848; 10689646; 10566645; 10999827; 10852446; 11549669; 12107222; 16551734; 20980225; 22508345; 22790459; 23057653; 23146819; 23291679; 23345044; 23441661; 23940125; 24022297 CYP11B2 2592 1585 Corticosterone methyloxidase type I deficiency; Corticosterone methyloxidase type II deficiency; Glucocorticoid-remediable aldosteronism AD/AR Pediatric Endocrine; Genitourinary; Oncologic Endocrine; Genitourinary; Oncologic Glucocorticoid-remediable aldosteronism involves a fusion gene (with CYP11B1) In Corticosterone methyloxidase deficiency, treatment of salt wasting (eg, with salt/mineralocorticoid supplementation) has shown success; In Glucocorticoid-remediable aldosteronism, medical treatment (eg, with glucocorticoids) can be beneficial; Surgical interventions may decrease the risk of gonadal tumors 14212087; 14250395; 295679; 4121586; 838841; 6268979; 2044581; 1731223; 1472060; 1601005; 1594605; 8439335; 7550315; 8825044; 9360501; 9814506; 10566645; 10999827; 10852446; 11238478; 12107222; 18178501; 19116236; 20494601; 22465514 CYP17A1 2593 1586 Adrenal hyperplasia, congenital, due to 17-alpha-hydroxylase deficiency AR Pediatric Endocrine;Genitourinary; Oncologic Endocrine; Genitourinary; Oncologic Individuals may not necessarily manifest with adrenal crisis, but mineralocorticoid excess may result in severe hypokalaemic hypertension, and awareness may allow preventive measures and treatment (eg, including glucocorticoids and mineralcorticoid antagonists); Treatment of genitourinary anomalies, as well as related hypogonadotrophic hypogonadism (eg, with hormone replacement therapy, as well as surgery in some individuals), can be beneficial; Due to risk of malignancy, gonadectomy may be indicated in genotypic males 4288776; 6039879; 4303304; 5456802; 999330; 6976525; 2843762; 2026124; 1648117; 2808364; 7629254; 8855840; 9360545; 9326943; 9177409; 11549685; 14671162; 16121340; 18559916; 20170344; 21823532; 22452398; 21550081; 22954317 CYP19A1 2594 1588 Aromatase deficiency AR Pediatric Allelic with Aromatase excess syndrome (AD), in which medical treatment (eg, with aromatase inhibitors) can be beneficial, but it is unclear if early (genetic) diagnosis would be advantageous Endocrine Endocrine Females may present with virilization resulting in manifestations such as pseudohermaphroditism , while males may present later with manifestations such as delayed skeletal maturation and epiphyseal closure, skeletal pain, eunuchoid habitus and increased adiposity, and estrogen therapy reverses symptoms 1825497; 8265607; 9543166; 12736278; 15811932; 17452968; 21521281; 21470988 CYP1A2 2596 1544 CYP1A2-related drug metabolism AD Pediatric General Pharmacogenomic Variants may also be related to subclinical metabolism of a number of agents (including medications), as well as related as a susceptibility factor; Porphyria cutanea tarda, severity of refersto a susceptibility locus and/or evidence or clinical applicability unclear 8035341; 10101295; 10233211; 10376760; 11153915; 12172216; 16522833; 17971810; 20881513; 20955109; 20147896; 19636338; 21121774; 19682433; 21989077 CYP1B1 2597 1545 Glaucoma 3A, primary congenital, A; Anterior segment dysgenesis 6 AR Pediatric Ophthalmologic Ophthalmologic; Pharmacogenomic Severe and difficult to treat glaucoma has been reported in many individuals with Peters anomaly; heterozygous variants may increase susceptibility to glaucoma; Digenic inheritance (with MYOC) has been reported; Variants may also act as disease modifiers (eg, related to Glaucoma, age of onset) Early diagnosis and treatment with surgery (with the use of pre and postoperative agents to control intraocular pressure), or, if surgery is not effective, drainage implants or cyclodestruction, may be effective to decrease morbidity and mortality related to vision loss; Agents that may contribute to glaucoma, as well as alpha-2-agonists, should be avoided 9097971; 9463332; 9497261; 10227395; 10655546; 11730663; 11403040; 12372064; 11774072; 15342693; 15733270; 17718864; 19807744; 19643970; 20301314; 21081970; 21600657; 22128238; 22942166; 23218701; 23363883; 24227805; 27839872 CYP21A2 2600 1589 Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency AR Pediatric Cardiovascular; Endocrine; Genitourinary; Oncologic Cardiovascular; Endocrine; Genitourinary; Oncologic In classic 21-OHD CAH, medical therapy (with glucocorticoid replacement), including with stress dosing glucocorticoid replacement therapy is beneficial; In the salt-wasting form, medical therapy (eg, with mineralocorticoid therapy, sodium chloride) can be beneficial; Surveillance and early treatment for neoplasms such as testicular adrenal rest tumors is indicated, as is surveillance related to multiple factors such as BMI, bone mineral density, fertility, and cardiovascular risk factors 13968788; 4298539; 835605; 152409; 6449518; 6102330; 317470; 6095106; 2989686; 3030300; 3491959; 3038528; 2667968; 2783976; 2247119; 1311000; 1644925; 7957400; 8855797; 8626833; 8923864; 9360525; 9329356; 9100612; 8989258; 9851787; 9661649; 9613359; 9829208; 10372672; 10084573; 10199755; 10720040; 11070100; 0720048; 11397874; 11232002; 11397897; 11739428; 12107196; 12213842; 12183722; 12788866; 12930931; 12915679; 12843131; 14764770; 16926248; 17299071; 17878254; 17535996; 17148562; 17456574; 8989258; 18381579; 20392211; 20301350; 22841790; 23073904; 22157069; 22241917; 22802425; 23044877; 22186144 CYP24A1 2602 1591 Hypercalcemia, infantile 1 AR Pediatric Endocrine; Renal Endocrine; Renal Individuals may present early in life with typical hypercalcemic signs/symptoms (eg, failure to thrive,dehydration, and muscular hypotonia or lethargy), or may present later with nephrolithiasis and nephrocalcinosis, and dietary measures, including avoidance of certain vitamin supplements (eg, vitamin D-containing compounds) to avoid hypercalcemia can be beneficial 3490596; 21675912; 22047572; 23293122 CYP26C1 20577 340665 Focal facial dermal dysplasia 4 AR N/A N/A Craniofacial; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16530710; 23161670 CYP27A1 2605 1593 Cerebrotendinous xanthomatosis AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic Biochemical; Cardiovascular The condition manifests with progressive neurologic dysfunction, as well as cardiovascular and ophthalmologic dysfunction, and medical treatment (eg, with chenodeoxycholic acid and HMG-CoA reductase inhibitors) can be beneficial 5636664; 5676919; 5355255; 4825231; 7315872; 7298854; 6504105; 3106810; 3128689; 1708392; 7847220; 7964884; 10430841; 11804206; 12555943; 11939886; 16278884; 18227423; 20301583; 20402754; 20450308; 20558929; 21553098; 22018287; 22336472; 23375591 CYP27B1 2606 1594 Vitamin D-dependent rickets, type 1A AR Pediatric Endocrine Endocrine Medical treatment with forms of vitamin D can be effective for prevention and treatment of manifestations, such as skeletal anomalies and seizures 6265615; 9486994 CYP2A6 2610 1548 CYP2A6-related drug metabolism AD Pediatric General Pharmacogenomic Selection and dosing of medications may be affected by the presence of variants 2322567; 9409631; 9827545; 10093988; 12042667; 12325023; 19238117; 23089672 CYP2B6 2615 1555 Efavirenz, poor metabolism of AD Pediatric General Pharmacogenomic It has been suggested that CYP2B6 genotype should be considered in efavirenz treatment 15622315; 20639527; 20860463; 23080225; 23152403 CYP2C19 2621 1557 Drug metabolism, CYP2C19-related AD Pediatric General Pharmacogenomic Selection and dosing of medications (eg, aspirin, clopidogrel, escitalopram, imipramine, omeprazole, tamoxifen) may be affected by the presence of variants 6489416; 3739364; 1302040; 8195181; 9093256; 16413245; 18004210; 18024866; 17625515; 19706858; 19106083; 19193675; 20083681; 20223877; 20978260; 20979470; 21047200; 19884907; 20351750; 20492469; 20801498; 20826260; 21178986; 21262992; 21288102; 21392617; 21288105; 21358751; 21700758; 21716271; 21716274; 21854540; 22027650; 22088980; 22228204; 22462746; 23090703; 23089672 CYP2C8 2622 1558 Drug metabolism, CYP2C8-related AD/AR Pediatric General Pharmacogenomic Selection and dosing of medications may be affected by the presence of variants; An individual with homozygosity for a frameshift variant developed acute rhabdomyolysis after cervistatin treatment; Patients with homozygous/compound heterozygous variant may be at risk for complications from medications including statins 15365880; 28378927 CYP2C9 2623 1559 Drug metabolism, CYP2C9-related AD Pediatric General Pharmacogenomic Selection and dosing of medications may be affected by the presence of variants 10073515; 10901705; 19228618; 19300499; 19715737; 19794412; 20089352; 20402581; 21562147; 23089672 CYP2D6 2625 1565 Drug metabolism, CYP2CD6-related AD Pediatric General Pharmacogenomic Variants may affect the metabolism of mulitple drugs including debrosoquine, sparteine, nortriptyline, codeine, tamoxifen 4082245; 1978251; 1673290; 8093319; 7903454; 9012401; 11940091; 15625333; 19809024 ; 22406651; 22733239; 22775532 CYP2R1 20580 120227 Vitamin D hydroxylation deficient rickets, type 1B AR Pediatric Endocrine Endocrine Medical treatment (eg, with supraphysiological levels of vitamin D3 or D2) has been reported to result in improvement or resolution of biochemical and clinical/radiographic anomalies 8201479; 15128933; 22855339 CYP2U1 20582 113612 Spastic paraplegia 56, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23176821 CYP3A4 2637 1576 Vitamin D-dependent rickets, type 3; Drug metabolism, CYP3A4-related AD Pediatric General Pharmacogenomic In Vitamin D-dependent rickets, medical management (eg, with high-dose calcitriol or vitamin D3) has been reporteed as beneficial; For Drug metabolism, CYP3A4-related, selection and dosing of medications (eg,colchicine) may be affected by the presence of variants 9789061; 18973929; 19337788; 19802823; 19907160; 20386561; 21047202; 20437462; 20440227; 21902501; 21902502; 21903774; 21946898; 29461981 CYP3A5 2638 1577 Drug metabolism, CYP3A5-related AD Pediatric General Pharmacogenomic Selection and dosing of many medications may be affected by the presence of variants 11740341; 15284534; 12065767; 20212519; 21412232; 22015057; 22210422; 22304537; 22407409; 22706623; 22875663; 23033116 CYP4F2 2645 8529 Warfarin metabolism AD Pediatric General Pharmacogenomic Selection and dosing of medications (warfarin) may be affected by the presence of variants 18250228; 19207028; 19300499; 22417713; 22534826; 22854539; 22855976 CYP4F22 26820 126410 Ichthyosis, congenital, autosomal recessive 5 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16436457 CYP4V2 23198 285440 Bietti crystalline corneoretinal dystrophy AR N/A N/A Ophthalmologic General Subclinical manifestations have been described in heterozygous individuals Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5299874; 306693; 3493804; 2783846; 11001583; 15042513; 18398705; 19508456; 21385027; 21565171; 22087103; 22497028; 22605929; 22693542; 22772592; 23143451; 23221965; 23242590; 23538635 CYP7B1 2652 9420 Bile acid synthesis defect, congenital, 3 AR Pediatric Allelic with Spastic paraplegia 5A, autosomal recessive (AR) Gastrointestinal; Neurologic Gastrointestinal Individuals may manifest with early-onset, progressive and severe cholestatic liver disease, and early recognition may allow treatment; Liver transplanation has been described 7987300; 9802883; 18252231; 19187859; 19439420; 21567895; 21623769; 22384504 CYTB 7427 4519 Myoglobinuria, recurrent; Leber hereditary optic neuropathy; Cardiomyopathy, infantile histiocytoid Maternal N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6093033; 1732158; 1764087; 9894887; 10502593; 10960495 D2HGDH 28358 728294 D-2-hydroxyglutaric aciduria 1 AR N/A N/A Biochemical; Cardiovascular; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15609246; 19169842; 20020533 DAAM2 18143 23500 Nephrotic syndrome, type 24 AR N/A N/A Renal General Steroid treatment has been described as ineffective Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33232676 DAB1 2661 1600 Spinocerebellar ataxia 37 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28686858 DACT1 17748 51339 Townes-Brocks syndrome 2 AD Pediatric Craniofacial; Gastrointestinal; Genitourinary; Renal Renal Individuals have been described with manifestations including vesicoureteral reflux, and surveillance and management may be helpful to preserve renal function 28054444 DAG1 2666 1605 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9; Muscular dystrophy-dystroglycanopathy, type C, 9 AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14678799; 21388311; 25503980; 25934851 DALRD3 25536 55152 Epileptic encephalopathy, early infantile, 86 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32427860 DARS1 2678 1615 Hypomyelination with brainstem and spinal cord involvement and leg spasticity AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23643384 DARS2 25538 55157 Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15326244; 17384640; 19592391; 21749991; 21815884; 22677571; 23065766; 23644316 DBH 2689 1621 Dopamine beta-hydroxylase deficiency AR Pediatric Biochemical; Genitourinary; Neurologic; Ophthalmologic; Renal Biochemical; Renal Medical therapy (eg, droxidopa) can effectively treat manifestations such as orthostatic hypotension; Surveillance of renal function should be instituted; For untreated individuals, circumstances such as vigorous exercise, hot environements, and dehydration should be avoided; In infantile-onset disease, awareness of hypotension, hypothermia, and hypoglycemia may be beneficial 3010116; 2890806; 2880016; 2300263; 2217667; 9651662; 16722595; 1677640; 11857564; 20063034; 20301647; 21471955 DBT 2698 1629 Maple syrup urine disease, type II AR Pediatric Biochemical; Neurologic Biochemical Dietary measures (eg, leucine restriction, high-calorie branched chain amino acid-free formulas, isoleucine and valine supplementation) combined with careful surveillance can be beneficial to prevent decompensation and minimize disease sequelae; Specific treatment in times of metabolic decompensation can reduce morbidity and mortaility; Liver transplantation is effective for classic MSUD; Specific monitoring is indicated in pregnancy 1847055; 1990841; 9621512; 11112664; 14517957; 14567968; 16786533; 20301495; 20946191; 22727569; 23313820 DCAF17 25784 80067 Woodhouse-Sakati syndrome AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Endocrine; Neurologic Cardiovascular; Endocrine Endocrine anomalies can include hypothyroidism and hypogonadism, and surveillance to allow appropriate medical care (eg, with replacement therapy, as well as care for manifestations such as diabetes mellitus) may be beneficial; Cardiac anomalies (including arrhythmia) have been reported, and surveillance and preventive measures may be beneficial; Awareness of hearing impairment may allow early interventions related to speech and language development 6876115; 7710875; 19026396; 18049083; 18175354; 20507343; 21963443; 21964978 DCAF8 24891 50717 Giant axonal neuropathy 2, autosomal dominant AD Adult Cardiovascular; Neurologic Cardiovascular Individuals have been described with cardiomyopathy, and awareness may allow early management 3859241; 24500646 DCC 2701 1630 Mirror movements 1; Gaze palsy, familial horizontal, with progressive scoliosis 2 AD/AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19127048; 19720981; 20431009; 21242494; 28250456 DCDC2 18141 51473 Deafness, autosomal recessive 66; Nephronophthisis 19; Sclerosing cholangitis, neonatal AR Pediatric Audiologic/Otolaryngologic; Gastrointestinal; Renal Audiologic/Otolaryngologic; Gastrointestinal In Nephronophthisis 19 and Sclerosing cholangitis, liver transplant has been described Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Nephronophthisis 19 and Sclerosing cholangitis, individuals may present with hepatic dysfunction, and awareness may allow early diagnosis and management 16244493; 25557784; 25601850; 27319779; 27469900 DCHS1 13681 8642 Mitral valve prolapse 2; Van Maldegrem syndrome 1 AD/AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal Audiologic/Otolaryngologic; Cardiovascular For Mitral valve prolapse, individuals may manifest with severe mitral valve prolapse leading to heart failure and requiring surgery, and awareness may allow prompt diagnosis and management; For Van Maldegrem syndrome, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12707861; 24056717; 26258302 DCLRE1C 17642 64421 Omenn syndrome; Severe combined immunodeficiency with sensitivity to ionizing radiation AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal Allergy/Immunology/Infectious Individuals typically present early in life with sequelae of infections, which are typically frequent and can be severe, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT may be beneficial 12055248; 12569164; 15731174; 19912631; 21184155 DCN 2705 1634 Corneal dystrophy, congenital stromal AD Adult Ophthalmologic Ophthalmologic In addition to other ophthalmologic care that may be effective (eg, penetrating keratoplasty), open-angle glaucoma has been described in several individuals, and awareness of this risk may allow surveillance and early treatment 5304426; 15671264; 16935612; 20301741; 21993463; 24413633 DCPS 29812 28960 Al-Raqad syndrome AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25701870; 25712129 DCT 2709 1638 Oculocutaneous albinism, type VIII AR N/A N/A Dermatologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33100333 DCTN1 2711 1639 Perry syndrome AD Adult Allelic with Neuropathy, distal hereditary motor, type VIIB (AD) Neurologic; Pulmonary Neurologic; Pulmonary In Perry syndrome, individuals may manifest with severe and potentially lethal hypoventilation, and interventions including aggressive pulmonary as well as medical management (eg, carbidopa/levodopa) may be beneficial 1122173; 43704; 3352925; 2247238; 11940687; 12627231; 15326253; 19136952; 20437543; 20702129; 20945553; 24343258 DCX 2714 1641 Lissencephaly, X-linked, 1 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9489699; 9489700; 9817918; 10430413; 10915612; 11175293; 12034802; 12552055; 19673952; 19050731; 19619967; 19673952; 20301364; 20726879; 21488284; 22408144; 25140959 DCXR 18985 51181 Pentosuria AR N/A N/A Biochemical General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22042873 DDB2 2718 1643 Xeroderma pigmentosum, group E AR Pediatric Dermatologic; Oncologic; Ophthalmologic Dermatologic; Oncologic Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance (primarily related to skin manifestations, as well as other sequelae) can be beneficial 3175673; 3339259; 8798680; 10447254; 20301571 DDC 2719 1644 Aromatic l-amino acid decarboxylase deficiency AR Pediatric Biochemical; Neurologic Biochemical Medical treatment (eg, with MAOI, dopamine agonists, and pyridoxine) has been reported as resulting in clinical improvement in some patients, largely with a milder form of disease, though functional clinical outcomes may be poor in many individuals 1700191; 1357595; 9309516; 12891654; 15079002; 20505134; 21963339; 31104889 DDHD1 19714 80821 Spastic paraplegia 28, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15786464; 23176821 DDHD2 29106 23259 Spastic paraplegia 54 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16636240; 23176823; 24482476 DDOST 2728 1650 Congenital disorder of glycosylation, type Ir AR Pediatric Biochemical; Gastrointestinal; Neurologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 22305527 DDR2 2731 4921 Warburg-Cinotti syndrome AD Pediatric Allelic with Spondylometaepiphyseal dysplasia, short limb-hand type (AR) Craniofacial; Dermatologic; Musculoskeletal; Ophthalmologic Dermatologic; Ophthalmologic It has been suggested that DDR2-inhibition (eg, via dasatinib), could be used for treatment of affected individuals 8434618; 19110212; 17103436; 20223752; 23637089; 30449416 DDRGK1 16110 65992 Spondyloepimetaphyseal dysplasia, Shohat type AR Pediatric Musculoskeletal; Pulmonary Pulmonary The condition may include a narrow trachea resulting in upper airway obstruction, and awareness may allow interventions to decrease morbidity and mortality 28263186 DDX11 2736 1663 Warsaw breakage syndrome AR N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General The condition can involve multiple congenital anomalies; It has been suggested that heterozygotes (and, presumably, homozygotes) may be at increased risk of malignancies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20137776; 23033317 DDX3X 2745 1654 Intellectual developmental disorder, X-linked, Snijders Blok type (Mental retardation, X-linked 102) XL N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25533962; 26235985 DDX41 18674 51428 Familial myeloproliferative/lymphoproliferative neoplasms, multiple types, susceptibility to AD Adult Allergy/Immunology/Infectious; Oncologic Oncologic Among other findings, individuals have been described with hematologic malignancies, and awareness may allow early detection and management 25920683; 26712909 DDX58 19102 23586 Singleton-Merten syndrome 2 AD Pediatric Cardiovascular; Dermatologic; Musculoskeletal; Ophthalmologic Cardiovascular; Ophthalmologic Among other manifestations, the condition can include cardiovascular calcifications, and awareness may allow early management (eg, surgical valvuloplasty has been described); Awareness of the risk of glaucoma can allow surveillance, prompt awareness and treatment 25620203 DDX59 25360 83479 Orofaciodigital syndrome V AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23972372 DDX6 2747 1656 Intellectual developmental disorder with impaired language and dysmorphic facies AD N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31422817 DEAF1 14677 10522 Vulto-van Silfout-de Vries syndrome; Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures AD/AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21076407; 23020937; 24726472; 26048982 DECR1 2753 1666 2,4-dienoyl-CoA reductase deficiency AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2332510 DEGS1 13709 8560 Leukodystrophy, hypomyelinating, 18 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30620337; 30620338 DENND5A 19344 23258 Developmental and epileptic encephalopathy 49 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27431290; 27866705 DEPDC5 18423 9681 Epilepsy, familial focal, with variable foci 1 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9851433; 10577924; 14510823; 15329069; 22780917; 23542697; 23542701; 24814846; 25623524 DES 2770 1674 Myopathy, myofibrillar 1; Cardiomyopathy, dilated, 1I AD/AR Pediatric Allelic with Scapuloperoneal syndrome, neurogenic, Kaeser type (AD) Cardiovascular; Musculoskeletal; Neurologic Cardiovascular In myofibrillar myopathy, individuals typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD); Cardiac transplantation may be necessary in individuals with severe forms of cardiomyopathy; In dilated cardiomyopathy, surveillance (eg, with electrocardiogram and echocardiogram) can allow early detection and interventions (including medications) in order to ameliorate morbidity and mortality 5828910; 8114783; 7672786; 9697706; 9736733; 10430757; 10545598; 11073539; 17221859; 17439987; 19433360; 19879535; 20301672; 20664348; 20718792; 22215463; 23687351; 24200904; 31024060 DGAT1 2843 8694 Diarrhea 7, protein-losing enteropathy type AR Pediatric Gastrointestinal Gastrointestinal Individuals may present in infancy with severe diarrhea, protein-losing enteropathy, metabolic acidosis, and electrolyte disturbances, and preventive measures and early treatment (including TPN) may be beneficial 23114594 DGCR2 2845 9993 Schizophrenia AD N/A N/A Neurologic General Evidence or clinical applicability unclear 21822266 DGKE 2852 8526 Nephrotic syndrome, type 7 AR Pediatric N/A Renal Renal Immunosuppressive therapy, as well as medical management (eg, with ACE inhibitors) have been described as beneficial in some individuals, but it is not clear that early (genetic) diagnosis would be beneficial; Renal transplant has been described In Hemolytic-uremic syndrome, some individuals have been described as responding to medical treatment (eg, immunosuppression, ACE inhibitors), and the choice of specific treatment modalitie, as well as decision to perform renal transplant, may be dictated by genetic diagnosis; Certain agents/precipitating factors should be avoided (eg, certain medications) 23274426; 23542698 DGUOK 2858 1716 Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) AR Pediatric Allelic with Portal hypertension, noncirrhotic (AR); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 (AR) Audiologic/Otolaryngologic; Biochemical; Gastrointestinal; Musculoskeletal; Neurologic Gastrointestinal In individuals with isolated liver disease, liver transplantation has been described as potentially beneficial, though there has been no reported survival advantage in instances of multisystem illness; Awareness may allow prompt recognition and treatment of manifestations such as neonatal hypoglycemia and hepatic dysfunction 11687800; 12205643; 15883261; 15887277; 16908739; 18205204; 18825706; 20301766; 21534344; 22137549; 22602837; 22622127; 22868686; 23043144; 23141463; 26874653 DHCR24 2859 1718 Desmosterolosis AR N/A N/A Biochemical; Craniofacial; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9450875; 11519011; 12457401; 21559050; 21671375 DHCR7 2860 1717 Smith-Lemli-Opitz syndrome AR Pediatric Biochemical; Cardiovascular; Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Renal Biochemical The condition may be recognizable by the constellation of manifestations Though the data are not definitive, anecdotal reports suggest that cholesterol supplementation and medical treatment (eg, with statins) may be clinically beneficial; Awareness of the potential for multiple malformations (some of which may be occult) may be beneficial to allow prompt recognition and management 14119520; 3812577; 8209913; 7632194; 7684480; 8831138; 8863875; 9024557; 9024564; 9024565; 9024566; 9130950; 9653161; 9683618; 11562938; 9634533; 9683613; 11161831; 10946022; 10951458; 11223857; 11167696; 12366604; 12407710; 15192627; 16761297; 17497248; 20301322; 18285838; 19430384; 20635399; 19365639; 20014133; 23042628; 23072947; 23162303; 23293579; 23319240; 23321614; 23426833; 23532938; 23538569; 23595802; 23688395; 23790112 DHDDS 20603 79947 Developmental delay and seizures with or without movement abnormalities; Retinitis pigmentosa 59 AD/AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21295282; 21295283; 29100083 DHFR 2861 1719 Megaloblastic anemia due to dihydrofolate reductase deficiency AR Pediatric Biochemical; Hematologic; Neurologic Biochemical The condition manifests with neurologic sequelae and megaloblastic anemia, and medical management (eg, with folinic acid) may help improve clinical parameters 21310276; 21310277 DHH 2865 50846 46,XY partial gonadal dysgenesis, with minifascicular neuropathy; 46,XY sex reversal 7 AD/AR Pediatric Endocrine; Genitourinary; Neurologic; Oncologic Endocrine; Genitourinary; Oncologic Heterozygous variants have been reported associated with mosaic 45,X/46,XY karyotypes Individuals may be at risk for oncologic processes related to gonadal tumors, and diagnosis and treatment (eg, with surgical removal) may be beneficial 11017805; 15356051; 16390857; 21816240 DHODH 2867 1723 Postaxial acrofacial dysostosis (Miller syndrome) AR N/A N/A Craniofacial; Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 501501; 19915526; 21346561; 22692683 DHPS 2869 1725 Neurodevelopmental disorder with seizures and speech and walking impairment AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30661771 DHS6S1 1 111365204 Macular dystrophy, retinal 1, North Carolina type AD N/A N/A Ophthalmologic General The condition is caused by a heterozygous variant in a DNase I hypersensitivity site (DHS6S1) upstream of PRDM13 Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1562260; 2622620; 9559736; 26507665 DHTKD1 23537 55526 Charcot-Marie-Tooth disease, axonal, type 2Q; Alpha-aminoadipic and alpha-ketoadipic aciduria AD/AR N/A N/A Biochemical; Musculoskeletal; Neurologic General In Alpha-aminoadipic and alpha-ketoadipic aciduria, dietary management (with protein restriction) has been reported, but it is not clear whether this was beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23141293; 23141294 DHX16 2739 8449 Neuromuscular disease and ocular or auditory anomalies with or without seizures AD N/A N/A Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31256877 DHX30 16716 22907 Neurodevelopmental disorder with severe motor impairment and absent language AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28327206; 29100085 DHX37 17210 57647 46, XY sex reversal 11; Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies AD/AR Pediatric Cardiovascular; Genitourinary; Musculoskeletal; Neurologic Cardiovascular; Genitourinary; Oncologic Among other findings, individuals with Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies have been reported as affected with arrhythmia and other cardiovascular anomalies, and awareness may allow prompt diagnosis and management; In 46, XY sex reversal 11, individuals may be at risk of gonadal neoplasms, and awareness may allow appropriate management 26539891; 31256877; 31287541; 31337883 DHX38 17211 9785 Retinitis pigmentosa 84 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24737827; 30208423 DIABLO 21528 56616 Deafness, autosomal dominant 64 AD N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21722859 DIAPH1 2876 1729 Deafness, autosomal dominant 1, with or without thrombocytopenia AD Pediatric Allelic with Seizures, cortical blindness, and microcephaly syndrome (SCBMS) (AR) Audiologic/Otolaryngologic; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Audiologic/Otolaryngologic Onset has been described as prelingual in some individuals, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 7211837; 1350680; 9360932; 22938506; 24781755; 26463574; 26912466; 28815995 DIAPH2 2877 1730 Premature ovarian failure 2A XL Pediatric Endocrine; Obstetric Obstetric Reported individuals have been affected with cytogenetic imbalances Genetic knowledge may allow fertility preservation such as by storing eggs 8406446; 9070928; 9497258 DICER1 17098 23405 DICER1 syndrome AD Pediatric Oncologic Oncologic Individuals are at risk for multiple malignancy types As individuals are at risk for a variety of neoplasms, surveillance and early diagnosis allowing early treatment of specific tumor types could potentially be beneficial 6261577; 799599; 9345104; 9295070; 18570301; 19556464; 21036787; 21266384; 21882293; 24761742 DIP2B 29284 57609 Mental retardation, FRA12A type AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4042396; 10955484; 17236128 DIS3L2 28648 129563 Perlman syndrome AR Pediatric Craniofacial; Musculoskeletal; Neurologic; Oncologic; Renal Oncologic Individuals may be affected by multiple congenital anomalies Individuals have a high risk of Wilms tumor, and surveillance may allow early detection and treatment, which may be beneficial 4315293; 163679; 6093533; 3024486; 10508986; 22306653; 22705997; 23486540; 23613427 DKC1 2890 1736 Dyskeratosis congenita, X-linked XL Pediatric Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic; Oncologic; Pulmonary Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; Lung transplant may be indicated in individuals with advanced lung diease; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal; Awareness of infectious risk may allow prompt diagnosis and treatment of infections 14096348; 5442429; 768476; 7272212; 6601257; 3009302; 3236366; 3201986; 1958493; 1361371; 1390173; 8318369; 7607282; 9590285; 8616066; 9042917; 9886310; 10583221; 10364516; 10700698; 12406104; 18005359; 18627054; 19415736; 19327580; 21415081; 20301779 DLAT 2896 1737 Pyruvate dehydrogenase E2 deficiency AR Pediatric Biochemical; Neurologic Biochemical Medical treatment (eg, with lipoic acid, thiamine, and ketogenic diet) has been reported as resulting in marked clinical improvement 2112155; 2112155; 20022530; 22896851; 23021068 DLD 2898 1738 Dihydrolipoyl dehydrogenase deficiency AR Pediatric Biochemical; Neurologic Biochemical The potential benefit of long-term medical treatment (eg, with riboflavin, biotin, coenzyme Q and carnitine) has been reported; Biochemical (but not clinical) improvement has been described with high-fat, low-protein diet with MCT oils and sodium dichloroacetate 3769994; 8506365; 8968745; 9298831; 9540846; 9934985; 11687750; 12925875; 14765544; 16770810; 16601893 DLG3 2902 1741 Mental retardation, X-linked 90 XL N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15185169; 24721225 DLG4 2903 1742 Intellectual developmental disorder, autosomal dominant 62 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20952458; 27479843; 29460436 DLL1 2908 28514 Holoprosencephaly; Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures AD N/A N/A Craniofacial; Endocrine; Musculoskeletal; Neurologic General Individuals with holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21196490; 31353024 DLL3 2909 10683 Spondylocostal dysostosis 1, autosomal recessive AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2805381; 10742114; 12746394; 15200511 DLL4 2910 54567 Adams-Oliver syndrome 6 AD N/A N/A Cardiovascular; Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26299364 DLST 2911 1743 Paragangliomas 7 AD Adult Oncologic Oncologic The condition can involve increased risk of parangangliomas, and awareness may allow early detection and management, which can reduce morbidity and mortality 30929736 DLX3 2916 1747 Trichodontoosseous syndrome; Amelogenesis imperfecta, type IV AD N/A N/A Craniofacial; Dental; Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9467018; 9783705; 10466415; 15666299; 18203197; 18362318; 18492670; 19608154; 21252474 DLX4 2917 1748 Orofacial cleft 15 AD N/A N/A Craniofacial General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25954033 DLX5 2918 1749 Split-hand/foot malformation 1 with sensorineural hearing loss AR Pediatric Audiologic/Otolaryngologic; Dental; Musculoskeletal Audiologic/Otolaryngologic The condition may be recognizable, but deafness may not be recognized as a component feature Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 22121204 DMD 2928 1756 Duchenne muscular dystrophy; Becker muscular dystrophy; Cardiomyopathy, dilated, 3B XL Pediatric Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular Cardiomyopathy is common in individuals, and has been specifically described as an isolated finding in females with relevant variants Individuals may present at varying ages and with varying degrees of severity, but due to risk of dilated cardiomyopathy, surveillance for manifestations (including with electrocardiogram and echocardiogram), including in asymptomatic individuals as well as variant-positive females, is recommended; For individuals with cardiomyopathy, treatment such as medical therapy, pacemakers, and ICD can decrease morbidity and mortality, and early recognition and treatment can improve outcomes, though some individuals with progressive/refractory disease may require cardiac transplantation 13249581; 6683357; 2879922; 3574369; 3612177; 3384440; 2404210; 2325103; 2180286; 1683155; 1518025; 8232953; 8361506; 7802009; 8198142; 8012195; 8789442; 9611069; 11726549; 9170407; 19367636; 19449031; 19367636; 20301298; 22428906; 22451200; 22609847; 22632414; 22650324; 23092449; 23299919 DMGDH 24475 29958 Dimethylglycine dehydrogenase deficiency AR N/A N/A Biochemical; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10102904 DMP1 2932 1758 Hypophosphatemic rickets, autosomal recessive 1 AR Pediatric Endocrine Endocrine Supplementation (eg, with phosphate and vitamin D) can be beneficial 17033621; 17033625 DMPK 2933 1760 Myotonic dystrophy 1 AD/AR Pediatric Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular; Ophthalmologic Individuals have been reported with fatal arrhythmias prior to other signs and symptoms, and cardiologic surveillance (including with EKG) and preventive measures may be beneficial; To assess for posterior capsular cataracts, segular ophthalmoscopy has been indicated, as these may require extraction if cataracts are impairing vision; if tarsorrhaphy is performed due to ptosis, it is important not to overcorrect due to risk of causing corneal abrasion secondary to lack of lid closure 1101835; 1167063; 6639233; 1346925; 1310900; 1346924; 1546326; 1346923; 1546325; 1303233; 8353490; 8503448; 8421476; 7696601; 7880334; 8071955; 7473648; 7650805; 8880582; 9106286; 9391889; 10325709; 11071501; 11807903; 15079005;15557517; 15596617; 17575483; 17663477; 18565861; 19949042; 19514047; 20018643; 20301344; 21259315; 22643181; 22995693 DMXL2 2938 23312 Polyendocrine-polyneuropathy syndrome AR Pediatric Allelic with Deafness, autosomal dominant, 71 (AD); Epileptic encephalopathy, early infantile, 81 (AR) Audiologic/Otolaryngologic; Craniofacial; Endocrine; Neurologic Endocrine Among other findings, individuals may manifest with hypothyroidism, early-onset hypoglycemia, and hypogonadotropic hypogonadism, and awareness may allow medical treatment of these endocrine diosrders 25248098; 27657680; 30237576; 31688942 DNA2 2939 1763 Progressive external ophthalmoplegia with mitochondrial deletions, autosomal dominant, 6; Seckel syndrome 8 AD/AR N/A N/A Biochemical; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23352259; 24389050 DNAAF1 30539 123872 Ciliary dyskinesia, primary, 13 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations 19944405; 19944400; 20301301 DNAAF11 16725 23639 Ciliary dyskinesia, primary 19 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations 23122589 DNAAF2 20188 55172 Ciliary dyskinesia, primary, 10 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 19052621; 20301301; DNAAF4 21493 161582 Ciliary dyskinesia, primary 25 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 23872636 DNAAF5 26013 54919 Ciliary dyskinesia, primary, 18 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 20350728; 23040496 DNAAF6 28570 139212 Ciliary dyskinesia, primary, 36 XL Pediatric Allergy/Immunology/Infectious; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Pulmonary Pulmonary surveillance may be beneficial to assess respiratory and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 28041644 DNAH1 2940 25981 Ciliary dyskinesia, primary, 37 AR Pediatric Allelic with Spermatogenic failure 18 (AR) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 24360805; 25927852; 27573432; 29449551 DNAH11 2942 8701 Ciliary dyskinesia, primary, 7 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 9585585; 12142464; 18022865; 20301301; 20513915; 22184204; 22499950 DNAH17 2946 8632 Spermatogenic failure 39 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31178125 DNAH2 2948 146754 Spermatogenic failure 45 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30811583 DNAH5 2950 1767 Ciliary dyskinesia, primary, 3 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 11788826; 16627867; 19300264; 19357118; 20301301; 22416021; 22499950 DNAH8 2952 1769 Spermatogenic failure 46 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32619401; 32681648 DNAH9 2953 1770 Ciliary dyskinesia, primary, 40 AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Individuals have been described with a relatively mild respiratory phenotype, but awareness may allow early diagnosis and prompt management of infections and related respiratory sequelae 30471717; 30471718 DNAI1 2954 27019 Ciliary dyskinesia, primary, 1 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 10577904; 11231901; 11893720; 16858015; 18434704; 19300264; 20301301; 21143860; 22416021; 22499950 DNAI2 18744 64446 Ciliary dyskinesia, primary, 9 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 18950741; 20301301; 23261302 DNAJB11 14889 51726 Polycystic kidney disease 6 with or without polycystic liver disease AD Adult Gastrointestinal; Renal Renal Renal transplant has been described Awareness may allow early identification of sequelae of renal disease in order to allow medical management 29706351 DNAJB13 30718 374407 Ciliary dyskinesia, primary, 34 AR Pediatric Allergy/Immunology/Infectious; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Pulmonary Pulmonary surveillance may be beneficial to assess respiratory function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 27486783 DNAJB2 5228 3300 Spinal muscular atrophy, distal, autosomal recessive, 5; Charcot-Marie-Tooth disease, axonal, type 2T AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22522442; 24627108; 25274842 DNAJB6 14888 10049 Muscular dystrophy, limb-girdle, type 1E AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22334415; 22366786; 24594375; 26205529; 30055862 DNAJC12 28908 56521 Hyperphenylalaninemia, mild, non-BH4-deficient AR Pediatric Biochemical Biochemical The condition can involve variable neurocognitive dysfunction, and individuals have been reported as benefiting from neurotrnsmitter precursors, especially if initiated in infancy 28132689; 28794131; 29174366; 30139987 DNAJC13 30343 23317 Parkinson disease 21 AD Adult Neurologic Neurologic Response to levodopa has been described 24218364; 25186792 DNAJC19 30528 131118 3-methylglutaconic aciduria, type V AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Genitourinary; Hematologic; Neurologic; Ophthalmologic Cardiovascular Individuals frequently demonstrate findings including cardiac manifestations such as dilated cardiomyopathy and dysrhythmias, and surveillance may allow early detection and management 16055927; 22981120 DNAJC21 27030 134218 Bone marrow failure syndrome 3 AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic Hematologic; Oncologic Individuals have been described with bone marrow failure, and awareness may allow prompt recognition and management related to hematologic (eg, anemia) and infectious sequelae; An individual has been described with AML, and awareness may allow prompt diagnosis and management; BMT has been described 27346687; 28062395; 29700810 DNAJC3 9439 5611 Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus AR N/A N/A Audiologic/Otolaryngologic; Endocrine; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25466870 DNAJC5 16235 80331 Ceroid lipofuscinosis, neuronal 4B, autosomal dominant AD N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5132971; 4414475; 62240; 932739; 11489285; 12112194; 21820099; 22073189; 22235333; 22978711 DNAJC6 15469 9829 Parkinson disease 19A, juvenile-onset AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22563501; 23211418 DNAL1 23247 83544 Ciliary dyskinesia, primary, 16 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations 20301301; 21496787 DNAL4 2955 10126 Mirror movements 3 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25098561 DNASE1L3 2959 1776 Systemic lupus erythematosus 16 AR N/A N/A Allergy/Immunology/Infectious General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22019780 DNM1 2972 1759 Developmental and epileptic encephalopathy 31 AD N/A N/A Neurologic General As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25262651; 25533962 DNM1L 2973 10059 Encephalopathy due to defective mitochondrial and peroxisomal fission 1; Optic atrophy 5 AD/AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15635063; 17460227; 28969390 DNM2 2974 1785 Charcot-Marie-Tooth disease, dominant intermediate B; Charcot-Marie-Tooth disease, axonal, type 2M; Myopathy, centronuclear, 1; Lethal congenital contracture syndrome 5 AD/AR N/A N/A Hematologic; Musculoskeletal; Neurologic; Ophthalmologic General Neutropenia has been described in several individuals Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11533912; 12481986; 12761657; 16227997; 15731758; 17932957; 18560793; 19122038; 20817456; 21221624; 22091729; 22396310; 22613877; 22924779; 23092955 DNMBP 30373 23268 Cataract 48 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30290152 DNMT1 2976 1786 Neuropathy, hereditary sensory, type IE; Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant AD N/A N/A Audiologic/Otolaryngologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7898717; 10210919; 21532572; 22328086; 22338191; 23365052 DNMT3A 2978 1788 Tatton-Brown-Rahman syndrome; Heyn-Sproul-Jackson syndrome AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24614070; 30478443 DNMT3B 2979 1789 Immunodeficiency-centromeric instability-facial anomalies syndrome 1 AR Pediatric Allergy/Immunology/Infectious; Neurologic Allergy/Immunology/Infectious Though the disorder may be clinically recognizable in many individuals, immunoglobulin supplementation can be beneficial, as can prophylaxis and early and aggressive treatment of infections 8076938; 10555141; 10647011; 11102980; 17893117 DOCK2 2988 1794 Immunodeficiency 40 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals are susceptible to frequent and severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been described 26083206 DOCK3 2989 1795 Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28195318; 29130632 DOCK6 19189 57572 Adams-Oliver syndrome 2 AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3354597; 21820096; 25132448; 25824905 DOCK7 19190 85440 Developmental and epileptic encephalopathy 23 AR N/A N/A Craniofacial; Neurologic General As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24814191 DOCK8 19191 81704 Hyper-IgE recurrent infection syndrome 2, autosomal recessive AR Pediatric Allelic with Mental retardation, autosomal dominant 2 (AD) Allergy/Immunology/Infectious; Neurologic; Oncologic Allergy/Immunology/Infectious; Oncologic Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; Individuals may also be at higher risk of oncologic complications, including lymphoma and squamous cell carcinomas, and awareness and surveillance may be beneficial in order to allow early detection and treatment; HSCT has been described 2338345; 14722525; 18060736; 18337720; 19776401; 23891736; 24104410; 24106060 DOK7 26594 285489 Myasthenic syndrome, congenital, 10 AR Pediatric Allelic with Fetal akinesia deformation sequence (AR), which likely represents an extreme phenotype of Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency Musculoskeletal; Neurologic Musculoskeletal; Neurologic; Pharmacogenomic Fetal akinesia deformation sequence 3 likely represents an extreme phenotype of Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency Unlike individuals with other types of genetic myasthenia, individuals with relevant DOK7 variants typically do not respond to chronic AChE inhibitor treatment, but other therapies (eg, albuterol, ephedrine, salbutamol) have been reported to result in marked clinical improvement; Agents that affect neuromuscular transmission and exacerbate myasthenic manifestations should be avoided; Additional neurologic monitoring in pregnancy may be beneficial 16917026; 18626973; 18707767; 19261599; 19837590; 20012313; 20301347; 20458068; 20554332; 20562457; 20610155; 22661499; 22884442; 22911480; 23108489; 23219351; 23657916; 23790237; 23831158 DOLK 23406 22845 Congenital disorder of glycosylation, type Im AR Pediatric Biochemical; Cardiovascular; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic Cardiovascular; Hematologic Hepatic-metabolized agents should be avoided In overall mildly affected individuals, cardiovascular manifestations such as dilated cardiomyopathy can result in severe sequelae, and early diagnosis may allow beneficial management; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 17273964; 22242004; 23890587 DONSON 2993 29980 Microcephaly, short stature, and limb abnormalities (MISSLA); Microcephaly-Micromelia syndrome AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28191891; 28630177 DPAGT1 2995 1798 Myasthenic syndrome, congenital, 13; Congenital disorder of glycosylation, type Ij AR Pediatric Biochemical; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Genitourinary Hematologic; Neurologic Hepatic-metabolized agents should be avoided Depending on the age of onset, individuals may present with findings such as hypotonia, gait problems, or falls, and medical treatment (eg, with anticholinesterases or agents that increase nerve terminal acetylcholine release) have been described as beneficial; In CDG, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 12872255; 16870884; 22742743; 23249953; 23278575 DPF2 9964 5977 Coffin-Siris syndrome 7 AD N/A N/A Craniofacial; Cardiovascular; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29429572 DPH1 3003 1801 Developmental delay with short stature, dysmorphic features, and sparse hair AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25558065; 26220823 DPM1 3005 8813 Congenital disorder of glycosylation, type Ie AR Pediatric Biochemical; Craniofacial; Neurologic; Ophthalmologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 642602; 10642597; 15669674; 16641202 DPM2 3006 8818 Congenital disorder of glycosylation, type Iu AR Pediatric Biochemical; Musculoskeletal; Neurologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 19901254; 23109149 DPM3 3007 54344 Muscular dystrophy-dystroglycanopathy, type C, 15 (Congenital disorder of glycosylation, type Io) AR Pediatric Allelic with Muscular dystrophy-dystroglycanopathy (congenital, with impaired intellectual development), type B, 15 (AR) Biochemical; Cardiovascular; Musculoskeletal; Neurologic Cardiovascular; Hematologic In a reported patient, dilated cardiomyopathy was the presenting complaint; Heart transplant has been described; Hepatic-metabolized agents should be avoided Dilated cardiomyopathy has been described, and awareness may allow early management; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 19576565; 28803818; 31266720; 31469168 DPP6 3010 1804 Ventricular fibrillation, paroxysmal familial, 2 AD Pediatric Allelic with Mental retardation, autosomal dominant 33 (AD) Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular Preventive measures and medical management may be helpful to help decrease morbidity; sudden cardiac death has been reported, including shortly following a normal cardiac examination 19285295; 23832105 DPY19L2 19414 283417 Spermatogenic failure 9 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15533374; 21397063; 21397064; 22627659; 22653751 DPYD 3012 1806 Dihydropyrimidine dehydrogenase deficiency AR Pediatric General Pharmacogenomic Homozygous/compound heterozygous variants can cause Dihydropyrimidine dehydrogenase deficiency; Severe toxicity can occur with certain medications (eg, 5-fluorouracil), and precautions may be beneficial 6488556; 2989687; 3335642; 8051923; 7832988; 9254861; 10027340; 10071185; 15303009; 19296131; 20544545; 20803296; 20920994; 21420945; 21553285; 21590448; 22410472; 22754590; 23042115 DPYS 3013 1807 Dihydropyriminidase deficiency AR Pediatric Biochemical; Neurologic Pharmacogenomic Affected individuals could theoretically have severe toxicity with 5-fluorouracil; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1770794; 9323563; 9266350; 9718352; 17383919; 20362666; 29054612 DRAM2 28769 128338 Cone-rod dystrophy 21 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25983245 DRC1 24245 92749 Ciliary dyskinesia, primary, 21 AR Pediatric Allergy/Immunology/Infectious; Pulmonary Allergy/Immunology/Infectious; Pulmonary Pulmonary surveillance may be beneficial to assess respiratory function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 23354437 DRD2 3023 1813 Myoclonic dystonia AD N/A N/A Musculoskeletal General Variants have been implicated in Myoclonic dystonia, though the data are mixed Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10220438; 10716258; 12402271; 20301587 DSC2 3036 1824 Arrhythmogenic right ventricular dysplasia, familial, 11 AD/AR Pediatric Cardiovascular; Dermatologic Cardiovascular Individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation 12392835; 17033975; 17186466; 18957847; 20197793; 20301310 DSC3 3037 1825 Hypotrichosis and recurrent skin vesicles AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19765682 DSE 21144 29940 Ehlers-Danlos syndrome, musculocontractural type 2 AR Pediatric Cardiovascular; Craniofacial; Dental; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular; Hematologic; Musculoskeletal Extrapolating from similar types of Ehlers-Danlos syndrome, clinical issues relate to connective tissue fragility may affect multiple organs related to bleeding diatheses (eg, after minor trauma), such that recognition may allow precautions and preventive measures, as well as rapid treatment 23704329 DSG1 3048 1828 Severe dermatitis, multiple allergies, and metabolic wasting syndrome (SAM syndrome) AR Pediatric Allelic with Keratosis palmoplantaris striata I (AD) Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Neurologic Allergy/Immunology/Infectious Among manifestations affecting multiple organ systems, the condition may include susceptibility to frequent and severe infections, and prophylactic measures and early and aggressive treatment of infections may be beneficial 7544663; 10332028; 11313759; 16484817; 17194569; 19018793; 19157795; 19558595; 20082890; 23974871 DSG2 3049 1829 Cardiomyopathy, dilated, 1BB; Arrhythmogenic right ventricular dysplasia, familial, 10 AD Pediatric Cardiovascular Cardiovascular In Arrhythmogenic right ventricular dysplasia, familial, 10, individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation; In Dilated cardiomyopathy; surveillance (eg, with echocardiography) may allow early detection of sequelae and medical management, which may decreased morbidity and mortality; Cardiac transplantation has been described 16773573; 16505173; 17105751; 18678517; 20301310 DSG3 3050 1830 Acantholytic blistering of the oral and laryngeal mucosa AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30528827 DSG4 21307 147409 Hypotrichosis 6 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12705872; 16543896; 16439973; 16575393; 17392831; 21495994 DSP 3052 1832 Arrhythmogenic right ventricular dysplasia, familial 8; Cardiomyopathy, dilated, with wooly hair and keratoderma; Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis AD/AR Pediatric Allelic with Keratosis palmoplantaris striata II (AD); Epidermolysis bullosa, lethal acantholytic (AR) Cardiovascular; Dermatologic Cardiovascular Homozygous/compound heterozygous variants reported as causing biventricular dilative cardiomyopathy with palmoplantar keratoderma and woolly hair (Skin fragility-woolly hair syndrome) Individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation 9738775; 9887343; 10902626; 11063735; 12373648; 11841538; 16175511; 16628197; 20940358; 21193976; 22527912; 22795705; 22949226 DSPP 3054 1834 Deafness, autosomal dominant, 39, with dentinogenesis imperfecta 1; Dentinogenesis imperfecta 1; Dentinogenesis imperfecta, Shields type III; Dentin dysplasia, type II AD N/A N/A Audiologic/Otolaryngologic; Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11175790; 11175779; 12354781; 15592686; 17686168; 18456718; 19026876; 19029076; 19103209; 19131317; 20121932; 20146806; 20618350; 20949630; 21029264; 21736673; 22125647; 22310900; 22521702 DST 1090 667 Epidermolysis bullosa simplex, autosomal recessive 2; Neuropathy, hereditary sensory and autonomic, type VI AR N/A N/A Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20164846; 22113475; 22522446 DSTYK 29043 25778 Congenital anomalies of the kidney and urinary tract, 1 AD Pediatric Neurologic; Renal Renal Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function 17273976; 23862974 DTNA 3057 1837 Left ventricular noncompaction 1 AD Pediatric Cardiovascular Cardiovascular The condition may affect cardiac function and may include arrhythmias, and surveillance (eg, with echocardiography and EKG), preventive measures, and medical management may be beneficial to decrease morbidity 11238270; 16427346 DTNBP1 17328 84062 Hermansky-Pudlak syndrome 7 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic Allergy/Immunology/Infectious; Dermatologic; Hematologic; Ophthalmologic Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Surveillance related to ophthalmologic and other manifestations has been recommended in all individuals with HPS 12923531; 20301464; 23364359 DUOX2 13273 50506 Thyroid dyshormonogenesis 6 AD/AR Pediatric Endocrine Endocrine Heterozygous variants have been reported as typically resulting in transient congenital hypothyroidism, while bi-allelic variants have been described as more frequently causing more severe and permanent forms of disease Individuals may manifest with congenital or subclinical hypothyroidism, and medical treatment (with thyroid hormone replacement) may be effective 12110737; 16134168; 21565790; 23239635; 23457309 DUOXA2 32698 405753 Thyroid dyshormonogenesis 5 AR Pediatric Endocrine Endocrine Medical treatment of hypothyroidism (eg, with T4) can be effective 18042646; 21367925; 23292166 DUSP6 3072 1848 Hypogonadotropic hypogonadism 19, with or without anosmia AD/Digenic Pediatric Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal; Neurologic Endocrine Relatively complex genetic models of disease have been described (eg, involving variants in other FGF8-network-associated genes) In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 23643382 DUX4 50800 100288687 Facioscapulohumeral muscular dystrophy, type 2 Digenic N/A N/A Musculoskeletal General Digenic inheritance has been described involving an SMCHD1 variant and a permissive D4Z4 haplotype Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23143600 DVL1 3084 1855 Robinow syndrome, autosomal dominant 2 AD N/A N/A Audiologic/Otolaryngologic; Craniofacial; Dental; Genitourinary; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10319206; 22431878; 25045061; 25817014; 25817016 DVL3 3087 1857 Robinow syndrome, autosomal dominant 3 AD N/A N/A Craniofacial; Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26924530 DYM 21317 54808 Dyggve-Melchior-Clausen disease; Smith-McCort dysplasia AR Pediatric Musculoskeletal; Neurologic Musculoskeletal Spinal cord compression due to atlantoaxial instability has been described, and awareness may allow screening and management to avoid potential sequelae 21032395; 1008064; 401564; 679519; 2213845; 1486701; 12491225; 12554689; 16470731; 19005420; 20865280; 22090722 DYNC1H1 2961 1778 Charcot-Marie-Tooth disease, axonal, type 2O; Mental retardation, autosomal dominant 13; Spinal muscular atrophy, lower extremity-predominant 1, autosomal dominant AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20697106; 21076407; 21820100; 22459677; 22368300; 25140959 DYNC2H1 2962 79659 Short-rib thoracic dysplasia 3 with or without polydactyly AR/Digenic N/A N/A Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal General Digenic variants in both NEK1 and DYNC2H1 can result in disease; The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19442771; 19361615; 21211617; 22499340; 22791528; 22499340 DYNC2I1 21862 55112 Short-rib thoracic dysplasia 8 with or without polydactyly AR N/A N/A Cardiovascular; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary; Renal General The condition may involve multiple malformations Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23910462 DYNC2I2 28296 89891 Short -rib thoracic dysplasia 11 with or without polydactyly AR N/A N/A Musculoskeletal; Ophthalmologic; Renal General Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24183449; 24183451 DYNC2LI1 24595 51626 Short-rib throacic dysplasia 15 with polydactyly AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26077881; 26130459 DYNLT2B 28482 255758 Short-rib thoracic dysplasia 17 with or without polydactyly AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27021811 DYRK1A 3091 1859 Mental retardation, autosomal dominant 7 AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18405873; 21294719; 23099646; 23160955 DYRK1B 3092 9149 Abdominal obesity-metabolic syndrome 3 AD Adult Cardiovascular; Endocrine Cardiovascular Individuals have been reported as being affected by coronary artery disease, as well as stroke/sudden death, at a relatively young age, and preventive measures and surveillance may allow early management, potentially reducing morbidity and mortality 24827035 DYSF 3097 8291 Miyoshi muscular dystrophy 1; Muscular dystrophy, limb-girdle, autosomal recessive, 2; Myopathy, distal, with anterior tibial onset AR Pediatric Cardiovascular; Musculoskeletal Cardiovascular Individuals may have mild cardiac anomalies, as well as more severe cardiac manifestations such as dilated cardiomyopathy, and surveillance (eg, with echocardiogram) may allow early detection and management of sequelae 3942856; 9009996; 8808603; 9731527; 9731526; 10196377; 10469840; 11134403; 10766988; 11198284; 16087766; 17287450; 17994539; 18306167; 19084402; 20535123; 21522182; 22297152; 22517428; 21816046 DZIP1 20908 22873 Mitral valve prolapse 3 AD Pediatric Allelic with Spermatogenic failure 47 (AR) Cardiovascular; Genitourinary Cardiovascular The condition can involve increased risk of mitral valve prolapse, and awareness may allow early diagnosis and management (eg, some individuals have required surgical management) 16172273; 31118289; 32051257 DZIP1L 26551 199221 Polycyctic kidney disease 5 AR Pediatric Renal Renal Individuals have been described with early-onset renal disease and failure, and awareness may allow early diagnosis and interventions; Renal transplant has been described 28530676 EARS2 29419 124454 Combined oxidative phosphorylation deficiency 12 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22492562; 23008233 EBF3 19087 253738 Hypotonia, ataxia, and delayed development syndrome (HADDS) AD N/A N/A Craniofacial; Genitourinary; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28017370; 28017372; 28017373 EBP 3133 10682 Chondrodysplasia punctata 2, X-linked dominant; Male EBP disorder with neurologic defects (MEND) XL N/A N/A Biochemical; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 830452; 535904; 10391219; 10391218; 11038443; 12503101; 12509714; 18573709; 21634086; 22121851; 22229330; 23307567; 24700572 ECE1 3146 1889 Hirschsprung disease, cardiac defects, and autonomic dysfunction AD N/A N/A Cardiovascular; Genitourinary; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9915973 ECEL1 3147 9427 Arthrogryposis, distal, type 5D AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23236030; 23261301; 25099528 ECHS1 3151 1892 Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25125611; 25393721; 26251176; 29575569 ECM1 3153 1893 Lipoid proteinosis AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Dermatologic; Neurologic; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5002423; 751090; 4087005; 11929856; 12603844; 19519837; 19734986; 21349189; 21791056; 21886756; 22182433 EDA 3157 1896 Ectodermal dysplasia, hypohidrotic, X-linked 1; Tooth agenesis, selective, X-linked, 1 XL N/A N/A Allergy/Immunology/Infectious; Craniofacial; Dental; Dermatologic General Frequent respiratory infections have been reported, possibly related to paucity/absence of mucus glands Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13913306; 5771499; 517571; 7446529; 2301459; 8434608; 8775234; 8696334; 9683615; 11388598; 17066260; 16583127; 17256800; 18657636; 18510547; 18231121; 18627052; 19533796; 22008666; 22350046 EDAR 2895 10913 Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant; Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive AD/AR N/A N/A Dental; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Hair morphology 1 is of unclear clinical significance 10431241; 15373768; 16029325; 18816645; 18231121; 20979233; 21771270; 21876339; 22032522 EDARADD 14341 128178 Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant; Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive AD/AR N/A N/A Dental; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9245989; 11780064; 17354266; 20979233; 21626677; 21876339 EDC3 26114 80153 Mental retardation, autosomal recessive 50 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25701870 EDN1 3176 1906 Question-mark ears, isolated; Auriculocondylar Syndrome 3 AD/AR N/A N/A Craniofacial General Conductive hearing loss has been described in one individual Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24268655 EDN3 3178 1908 Waardenburg syndrome, type 4B; Central hypoventilation syndrome, congenital; Hirschsprung disease, susceptibility to, 4 AD/AR Pediatric Audiologic/Otolaryngologic; Dermatologic; Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary Audiologic/Otolaryngologic; Gastrointestinal; Neurologic; Pulmonary Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In conditions that may involve Hirschsprung disease, recognition of potential GI anomalies (eg, aganglionosis) may allow prompt recognition and treatment; In Central hypoventilation syndrome, congenital, early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality 8696331; 8630502; 8630503; 9279758; 9359047; 10231870; 11303518; 19764030; 20009762 EDNRA 3179 1909 Mandibulofacial dysostosis with alopecia AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Ophthalmologic Audiologic/Otolaryngologic Among other features, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 16116593; 20583178; 25772936 EDNRB 3180 1910 Waardenburg syndrome type 4A; ABCD syndrome; Hirschsprung disease, susceptibility to, 2 AD/AR Pediatric Audiologic/Otolaryngologic; Dermatologic; Gastrointestinal; Ophthalmologic Audiologic/Otolaryngologic; Gastrointestinal Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Recognition of potential GI manifestations (eg, Hirschsprung disease) may allow prompt treatment 7264803; 8001158; 8634719; 7778600; 10528251; 11484199; 11891690; 19764031 EED 3188 8726 Cohen-Gibson syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25787343; 27193220; 27868325; 28229514 EEF1A2 3192 1917 Developmental and epileptic encephalopathy 33; Mental retardation, autosomal dominant 28 AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23033978; 23647072; 24697219 EEF2 3214 1938 Spinocerebellar ataxia 26 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15732118; 23001565 EFEMP1 3218 2202 Doyne honeycomb degeneration of retina AD N/A N/A Ophthalmologic General Photodynamic therapy may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10369267; 11384588; 11389162; 11825812; 12431256; 17666404; 22581936; 23036572 EFEMP2 3219 30008 Cutis laxa, autosomal recessive type IB AR Pediatric Cardiovascular; Dermatologic; Musculoskeletal; Pulmonary Cardiovascular Manifestations can include cardiovascular anomalies, including aortic dilatation and aortic aneurysms, and surveillance may allow early detection and management (eg, with beta-blockers and angiotensin-receptor inhibitors), which can decrease morbidity and mortality; Cigarette smoking should be avoided due to risk of exacerbation of pulmonary manifestations (including emphysema) 16685658; 17937443; 19664000; 20389311; 21563328; 22440127; 23212998 EFHC1 16406 114327 Myoclonic epilepsy, juvenile, susceptibility to, 1; Epilepsy, juvenile absence, susceptibility to, 1 AD N/A N/A Neurologic General As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7668263; 12439895; 15258581; 17159113; 18505993; 19147686; 22690745; 22727576; 22926142 EFL1 25789 79631 Shwachman-Diamond syndrome 2 AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Gastrointestinal; Hematologic Medical treatment (eg, pancreatic enzymes, fat-soluble vitamins) can be effective to treat pancreatic exocrine insufficiency; Blood/platelet transfusions may be necessary; Due to neutropenia and infectious risk, prophylactic measures (eg antibiotics), as well as early and aggressive treatment of infections, may be beneficial 28331068 EFNB1 3226 1947 Craniofrontonasal dysplasia XL N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15166289; 15124102; 15959873; 16639408; 17941886; 18627045; 20734337; 21385071; 23509643 EFTUD2 30858 9343 Mandibulofacial dysostosis, Guion-Almeida type AD Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic Audiologic/Otolaryngologic The condition may frequently be recognizable due to the presence of specific manifestations Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Recognition of potential GI manifestations (eg, Hirschsprung disease) may allow prompt treatment 16760738; 19334086; 22541558; 22305528; 23188108; 25790162 EGF 3229 1950 Hypomagnesemia 4, renal AR Pediatric Renal Renal Children may present with tetany and/or convulsions, and failure of early diagnosis (or treatment noncompliance) can be fatal or result in permanent neurological damage due to electrolyte abnormalities; Replacement therapy may be beneficial 3436090; 17671655 EGFR 3236 1956 Inflammatory skin and bowel disease, neonatal, 2 AR Pediatric Allergy/Immunology/Infectious; Cardiovascular Allergy/Immunology/Infectious; Cardiovascular In familial AML, one family has been reported, in which there was an inherited genomic ERBB rearrangement In Inflammatory skin and bowel disease, neonatal, 2, antiinfectious prophylaxis andearly and aggressive treatment of infections may be beneficial, and individuals may also have cardiovascular manifestations such that surveillance may allow beneficial interventions 10686940; 16258541; 24691054 EGLN1 1232 54583 Erythrocytosis, familial, 3 AD Pediatric Allelic with Hemoglobin, high altitude adapation (AR) Hematologic; Oncologic Hematologic; Oncologic In some described individuals, it has been suggested that manifestations involved increased risk of neoplasms as well as hematologic manifestations Phlebotomy can be used to maintain the hematocrit value in the desired range; Due to a reported increased risk of neoplasms, awareness may allow early detection and management, which may decrease associated morbidity and mortality 16407130; 17579185; 19092153; 20301715; 20466884; 20595611; 21275967; 21828119; 21904933; 25129147 EGR2 3239 1959 Charcot-Marie-Tooth disease, demyelinating, type 1D; Neuropathy, congenital hypomyelinating, 1, autosomal recessive; Dejerine-Sottas disease AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9537424; 10369870; 10371530; 11523566; 15947997; 21840889; 22271166; 22522483; 22546699; 22734907 EHHADH 3247 1962 Fanconi renotubular syndrome 3 AD Pediatric Renal Renal Manifestations in the described individuals can include severe rickets, and early knowledge may allow medical/dietary interventions (eg, with calcitriol, and phosphate supplementation) to prevent (and treat) this complication 1627757; 24401050 EHMT1 24650 79813 Kleefstra syndrome 1 AD N/A N/A Cardiovascular; Musculoskeletal; Neurologic General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16826528; 19264732; 21910222; 22670143; 23232695 EIF2AK1 24921 27102 Leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32197074 EIF2AK2 9437 5610 Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32197074 EIF2AK3 3255 9451 Epiphyseal dysplasia, multiple, with early-onset diabetes mellitus (Wolcott-Rallison syndrome) AR Pediatric Cardiovascular; Dental; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Renal Endocrine Individuals can have infantile-onset insulin-dependent diabetes mellitus (and may present with severe sequelae of diabetes, which may lead to death) prior to obvious manifestation of other, recognizable features, and prompt recognition and treatment could decrease morbidity and mortality, though treatment can be challenging 5008828; 7094931; 7551159; 9598721; 10932183; 12960215; 16813601; 21050479; 21648287; 21518408; 22672868; 23759358 EIF2AK4 19687 440275 Pulmonary venoocclusive disease 2 AR Pediatric Cardiovascular; Pulmonary Cardiovascular; Pulmonary Medical treatment (eg, with calcium antagonists, anticoagulants, prostanoids, endothelin receptor antagonists, etc.) may be beneficial, though lung transplantation may be required 24292273 EIF2B1 3257 1967 Leukoencephalopathy with vanishing white matter AR Pediatric Endocrine; Neurologic; Obstetric Obstetric The evidence is unclear, but it is possible that certain circumstances may aggravate the condition and accelerate neurological decline, including head trauma (children may benefit from wearing helmets), contact sports, and stressful situations (including high body temperature, and prophylactic measures and rapid treatment related to infections may be beneficial) Individuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired 11704758; 11835386; 18263758; 20301435 EIF2B2 3258 8892 Leukoencephalopathy with vanishing white matter AR Pediatric Endocrine; Neurologic; Obstetric Obstetric The evidence is unclear, but it is possible that certain circumstances may aggravate the condition and accelerate neurological decline, including head trauma (children may benefit from wearing helmets), contact sports, and stressful situations (including high body temperature, and prophylactic measures and rapid treatment related to infections may be beneficial) Individuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired 11704758; 11835386; 14566705; 15054402; 18263758; 19625339; 21484434; 22285377; 20301435; 22678813; 22729508 EIF2B3 3259 8891 Leukoencephalopathy with vanishing white matter AR Pediatric Endocrine; Neurologic; Obstetric Obstetric The evidence is unclear, but it is possible that certain circumstances may aggravate the condition and accelerate neurological decline, including head trauma (children may benefit from wearing helmets), contact sports, and stressful situations (including high body temperature, and prophylactic measures and rapid treatment related to infections may be beneficial) Individuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired 11704758; 11835386; 15136673; 18263758; 19158808; 20301435; 21484434; 22312164; 23115207 EIF2B4 3260 8890 Leukoencephalopathy with vanishing white matter AR Pediatric Endocrine; Neurologic; Obstetric Obstetric The evidence is unclear, but it is possible that certain circumstances may aggravate the condition and accelerate neurological decline, including head trauma (children may benefit from wearing helmets), contact sports, and stressful situations (including high body temperature, and prophylactic measures and rapid treatment related to infections may be beneficial) Individuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired 11704758; 11835386; 14566705; 15054402; 15776425; 18263758; 20301435 EIF2B5 3261 8893 Leukoencephalopathy with vanishing white matter AR Pediatric Endocrine; Neurologic; Obstetric Obstetric The evidence is unclear, but it is possible that certain circumstances may aggravate the condition and accelerate neurological decline, including head trauma (children may benefit from wearing helmets), contact sports, and stressful situations (including high body temperature, and prophylactic measures and rapid treatment related to infections may be beneficial) Individuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired 11704758; 12325082; 11835386; 14694060; 12707859; 14566705; 15054402; 15136673; 15136690; 15776425; 18263758; 19625339; 20301435; 20975056; 21676421; 22699478 EIF2S3 3267 1968 MEHMO syndrome XL Pediatric Craniofacial; Endocrine; Musculoskeletal; Neurologic Endocrine Awareness of endocrine manifestations, including growth hormone deficiency and hypogonadism, may allow early recognition and treatment 23063529; 27333055; 28055140 EIF3F 3275 8665 Intellectual developmental disorder 67 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30409806 EIF4A3 18683 9775 Richieri-Costa-Pereira Syndrome AR N/A N/A Craniofacial; Musculoskeletal General The genetic cause involves a noncoding expansion Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24360810 EIF4E 3287 1977 Autism, susceptibility to, 19 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19556253 EIF4G1 3296 1981 Parkinson disease 18 AD Adult Neurologic Neurologic Response to levodopa has been described, though the evidence for causation is mixed 21907011; 23408866; 25227500; 25368108 ELAC2 14198 60528 Combined oxidative phosphorylation deficiency 17 AR Pediatric Biochemical; Cardiovascular; Neurologic Biochemical; Cardiovascular The condition can include severe cardiac sequelae, such as hypertrophic cardiomyopathy, and though some individuals have been described as not responding to therapy, others have been reported as benefitting from cardiac surveillance and early insitution of cardioprotective therapy and and biochemical dietary and medical treatment (eg, high-fat diet, coenzyme Q10, riboflavin, thiamine, and carnitine) 23849775 ELANE 3309 1991 Neutropenia, severe congenital 1, autosomal dominant; Neutropenia, cyclic AD Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic Antiinfectious prophylaxis (including GCSF and related therapies) and early and aggressive treatment of infections may be beneficial; Surveillance and early treatment for malignancy may be beneficial; HSCT has been described for severe congenital neutropenia 13575153; 6050865; 4319697; 2471075; 2469956; 1282277; 8490166; 7529539; 8541539; 8989458; 8624368; 9116280; 9386665; 10581030; 11001877; 10887102; 17063141; 18028488; 17133096; 18611981; 19036076; 21072829; 22148006; 22080845; 22510773; 22624626; 22758217; 23454784; 23463630 ELMO2 17233 63916 Vascular malformation, primary intraosseus AR Pediatric Cardiovascular; Musculoskeletal Cardiovascular The condition involves vascular malformation often affecting the vertebral column and the skull, with life-threatening complications after tooth extraction as well as spontaneous severe bleeding episodes, and awareness may allow preventive measures and aggressive management, which may ameliorate morbidity and mortality 11932989; 27476657 ELMOD3 26158 84173 Deafness, autosomal recessive 88 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 24039609 ELN 3327 2006 Cutis laxa, autosomal dominant 1; Supravalvular aortic stenosis AD Pediatric Cardiovascular; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary Cardiovascular Individuals with Cutis Laxa may have a clinically recognizable phenotype, In Cutis laxa, cardiovascular anomalies (eg, aortic aneuryms and pulmonary artery stenosis) are frequent, and surveillance to allow efficient detection and treatment/precautionary measures may be beneficial; In supravalvular aortic stenosis, there is a wide range of severity, including sudden infant death, and early diagnosis and treatment (eg, with surgery in some individuals) may reduce morbidity and mortality 5046633; 8475063; 8362925; 8364568; 8091333; 8132745; 8541862; 9215670; 9215671; 9873040; 11175284; 15955094; 16085695; 18348261; 19844261 ELOVL1 14418 64834 Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies AD N/A N/A Craniofacial; Dermatologic; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29496980; 30487246 ELOVL4 14415 6785 Ichthyosis, spastic quadriplegia, and mental retardation; Spinocerebellar ataxia 34; Startgardt disease 3 AD/AR N/A N/A Biochemical; Dermatologic; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10634627; 11726641; 11138005; 15557430; 22100072; 24566826 ELOVL5 21308 60481 Spinocerebellar ataxia 39 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25065913 ELP1 5959 8518 Neuropathy, hereditary sensory and autonomic, type III AR N/A N/A Craniofacial; Neurologic; Renal General One report has described possible increased tumorigenesis in affected individuals; Individuals may be prone to injury due to pain insensitivity Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18118947; 14071043; 14245781; 4322121; 7374014; 7254974; 7097419; 3585611; 11179021; 11179008; 12406829; 12546638; 15088259; 19651702; 19914433; 20301359; 22129610; 22170819; 22229594; 22571291; 22727867; 22739220; 22850346 ELP2 18248 55250 Mental retardation, autosomal recessive 58 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21937992; 25847581 ELP4 1171 26610 Aniridia 2 AD Pediatric Ophthalmologic Ophthalmologic; Pharmacogenomic The condition has been reported as caused by an intronic variant in a PAX6 cis-regulatory element Individuals with PAX6 related eye anomalies (including due to cis-regulatory variants in ELP4) may be recognizable, but some may also be at high risk of developing glaucoma; Agents that may contribute to glaucoma should be avoided 24290376 EMC1 28957 23065 Cerebellar atrophy, visual impairment, and psychomotor retardation AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26942288 EMC10 27609 284361 Neurodevelopmental disorder with dysmorphic facies and variable seizures AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Renal anomalies have been described in some individuals, but it is unclear if these are related to EMC10 Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32869858; 33531666 EMD 3331 2010 Emery-Dreifuss muscular dystrophy 1, X-linked XL Pediatric Cardiovascular; Musculoskeletal Cardiovascular Individuals, including females, can have serious cardiac conduction defects Surveillance for and treatment of cardiac disease (eg, with EKG), including pacemaker implantation, may be beneficial 4567289; 3319295; 2685312; 7894480; 9195226; 10377322; 10323252; 10382910; 20301609; 21496632; 21697856 EMG1 16912 10436 Bowen-Conradi syndrome AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 974244; 484596; 12838567; 15578624; 19463982 EML1 3330 2009 Band heterotopia AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24859200 EMP2 3334 2013 Nephrotic syndrome, type 10 AR N/A N/A Renal General Management with cyclophosphamide has been described as beneficial (frequent relapses have been described with steroid treatment) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24814193 EMX2 3341 2018 Schizencephaly AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8528262; 9359037; 17506092; 18409201 EN1 3342 2019 ENDOVE syndrome, limb-brain type AR Pediatric Allelic with ENDOVE syndrome, limb-only type (AR) Musculoskeletal; Neurologic; Renal Renal The conditions are due to deletions and genomic rearrangements of a domain upstream of EN1 Among other findings, an individual has been described with bilateral hydronephrosis and recurrent urinary tract infections, and awareness may allow eaerly diagnosis, preventative measures, and management of infections 33568816 ENAM 3344 10117 Amelogenesis imperfecta, type IB; Amelogenesis imperfecta, type IC AD/AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11487571; 11978766; 14684688; 22243262 ENG 3349 2022 Hereditary hemorrhagic telangiectasia, type 1 AD Pediatric Cardiovascular; Gastrointestinal; Hematologic Hematologic Oncologic complications have been reported (in Juvenile polyposis syndrome), but the evidence appears overall unclear Individuals may have a variety of vascular complications, such as arteriovenous malformations (eg, pulmonary arteriovenous malformations, which can lead to a number of complications, including cerebral abscesses) and bleeding diatheses, and surveillance and early intervention related to manifestations (eg, related to thromboembolism or hepatic disease) may decrease morbidity and mortality 5656734; 4834927; 4050544; 3186989; 2658618; 2729347; 2036743; 1518020; 7894484; 7666879; 9354504; 9541302; 9753031; 10636073; 11006369; 12920067; 15024723; 16287957; 16470787; 16752392; 16155196; 16542389; 17204053; 18831062; 18312453; 19439755; 20301525; 23380110; 23440993; 23722869; 23919827; 23962120; 24001356 ENO3 3354 2027 Glycogen storage disease XIII AR N/A N/A Biochemical; Musculoskeletal General The reported individual had exercise intolerance and increased CK without myoglobinuria Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11506403 ENPP1 3356 5167 Hypophosphatemic rickets, autosomal recessive 2; Arterial calcification, generalized, of infancy, 1 AR Pediatric Allelic with Cole disease (AD) Cardiovascular; Dermatologic; Musculoskeletal; Renal Renal For hypophosphatemic rickets, treatment (eg, with phosphates, vitamin D supplements) may be effective; In Arterial calcification, generalized, of infancy, 1, bisphosphonates have been described as beneficial in some 11159191; 12881724; 15940697; 19380683; 20016754; 19206175; 20137772; 20137773; 21745613; 21932012; 22629037; 22229486; 22209248; 24075184 ENTPD1 3363 953 Spastic paraplegia 64 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24482476 EOGT 28526 285203 Adams-Oliver syndrome 4 AR N/A N/A Cardiovascular; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23522784 EP300 3373 2033 Rubinstein-Taybi syndrome 2; Menke-Hennekam syndrome 2 AD Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Audiologic/Otolaryngologic The condition may include a risk of malignancy and frequent infections, as well as arrhythmia Rubinstein-Taybi syndrome can include a risk of frequent infections (especially respiratory infections), and prophylaxis and early and aggressive treatment of infections may be beneficial; Menke-Hennekam syndrome can include frequent infections, and prophylaxis and early and aggressive treatment of infections may be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 15706485; 17299436; 17220215; 19353645; 20014264; 20301699; 20717166; 21376300; 24352918; 25712426; 27465822; 29460469 EPAS1 3374 2034 Erthyrocytosis, familial 4 AD Pediatric Hematologic; Oncologic Hematologic; Oncologic While presentation is typically described in adulthood, surveillance and treatment may be indicated in the pediatric time period Individuals can present with manifestations secondary to erythrocytosis (eg, a DVT has been described in one individual), and interventions related to erythrocytosis (eg, venesection) have been described as beneficial; Due to a reported increased risk of neoplasms (eg, pheochromocytoma/paraganglioma), awareness may allow early detection and management, which may decrease associated morbidity and mortality 7747773; 18184961; 18456918; 18378852; 23090011 EPB41 3377 2035 Ellipsocytosis 1 AR Pediatric Hematologic Hematologic The recessive form is more severe, and due to anemia, individuals may require transfusions, and/or splenectomy 5731934; 7255153; 6894932; 7082842; 3965051; 3995181; 3755799; 3748797; 3674005; 1430200; 16730867; 14692233; 21839655 EPB41L1 3378 2036 Mental retardation, autosomal dominant 11 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21376300 EPB42 3381 2038 Spherocytosis, type 5 AR Pediatric Hematologic Hematologic Due to anemia, individuals may require transfusions and/or splenectomy 4830746; 4413274; 2963832; 2386772; 2139792; 1558976; 7803799; 7772513; 9734643; 10406914; 12176912; 14636652; 19269200; 21275958 EPCAM 11529 4072 Colorectal cancer, hereditary nonpolyposis, type 8; Diarrhea 5, with tufting enteropathy, congenital AD/AR Pediatric Gastrointestinal; Musculoskeletal; Oncologic Gastrointestinal; Oncologic Specific deletions result in MSH2 inactivation; Although Colorectal cancer, hereditary nonpolyposis, type 8 typically manifests in adulthood, individuals have been reported such that familial screening would be recommended to commence during the pediatric period; Diarrhea 5, with tufting enteropathy, congenital may include additional features, such as dysmorphism In HNPCC, for surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types, awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; In Diarrhea 5, with tufting enteropathy, congenital, most affected individuals require parenteral nutrition for normal growth and development, and awareness can allow prompt medical/nutritional support 100367; 8057225; 16951683; 18572020; 19820410; 19098912; 20388775; 20301390; 21309036; 21227399 EPG5 29331 57724 Vici syndrome AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Surveillance for cardiomyopathy (eg, including echocardiogram) may allow early management; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 20186778; 23222957; 27343256; 28168853 EPHA2 3386 1969 Cataract 6, multiple types AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19005574; 19649315; 20361013 EPHB2 3393 2048 Bleeding disorder, platelet-type, 22 AR Pediatric Hematologic Hematologic Individuals have been described with spontaneous subcutaneous bleeding as well as excessive bleeding after minor injuries, and awareness may allow preventative measures to avoid sequelae, as well as other management options (e.g., iron treatment has been described in one patient) 30213874 EPHB4 3395 2050 Capillary malformation-arteriovenous malformation 2 AD Pediatric Allelic with Lymphatic malformation 7 (AD) Cardiovascular Cardiovascular Life-threatening complications of arteriovenous malformations and arteriovenous fistulas can include bleeding, congestive heart failure, and/or neurologic consequences, and surveillance may allow early detection and medical/surgical management, which may decrease morbidity/mortality 27400125; 28687708; 28730721; 29444212 EPHX1 3401 2052 Hypercholanemia, familial AR Pediatric Gastrointestinal Gastrointestinal As in other forms of familial hypercholanemia, individuals may respond to medical treatment (eg, with ursodeoxycholic acid) 12878321; 15768832 EPM2A 3413 7957 Epilepsy, progressive myoclonic 2A (Lafora) AR N/A N/A Neurologic General Some antiepileptic drugs may be effective, but certain medications (eg, phenytoin, and possibly carbamazepine, oxcarbazepine, and lamotrigine) can exacerbate myoclonus Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9771710; 10513696; 14663053; 15277643; 16157917; 16356781; 20301563 EPO 3415 2056 Erythrocytosis, familial, 5; Diamond-Blackfan anemia-like AD/AR Pediatric Hematologic Hematologic For Erythrocytosis, phlebotomy can be used to maintain the hematocrit value in the desired range; Individuals with Diamond-Blackfan anemia-like may benefit from medical management (recombinant EPO has been described), and HSCT has been reported 27651169; 28283061; 29514032 EPOR 3416 2057 Erythrocytosis, familial, 1 AD Pediatric Hematologic Hematologic Phlebotomy can be used to maintain the hematocrit value in the desired range 4052634; 1954391; 093406; 9292543; 9649565; 20700488; 21437635 EPRS1 3418 2058 Leukodystrophy, hypomyelinating, 15 AR N/A N/A Audiologic/Otolaryngologic; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29576217 EPS8 3420 2059 Deafness, autosomal recessive 102 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 24741995 EPS8L2 21296 64787 Deafness, autosomal recessive 106 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Prelingual hearing loss has been described in some (but not all) individuals Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 26282398 EPX 3423 8288 Eosinophil peroxidase deficiency AR N/A N/A General General The clinical relevance is unclear 7809065 ERAL1 3424 26284 Perrault syndrome 6 AR Pediatric Audiologic/Otolaryngologic; Obstetric Audiologic/Otolaryngologic; Obstetric Hearing loss has been described in early childhood, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Genetic knowledge may allow fertility preservation such as by storing eggs in woman with premature ovarian failure 28449065 ERBB3 3431 2065 Erythroleukemia, familial, susceptibility to AD N/A Allelic with Lethal congenital contracture syndrome 2 (AR) Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Oncologic; Renal Hematologic; Oncologic Individuals with Lethal congenital contracture syndrome 2 can have manifestations including cardiovascular anomalies (eg,cardiomyopathy and ventricular septal defects have been described) and hydronephrosis without urinary bladder abnormality The condition can involve hematologic anomalies and predisposition to certain forms of cancer, and awareness may allow prompt diagnosis and management 3471269; 6948132; 12548738; 17701904; 27416908 ERBB4 3432 2066 Amyotrophic lateral sclerosis 19 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24119685 ERCC1 3433 2067 Cerebrooculofacioskeletal syndrome 4 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17273966; 23623389 ERCC2 3434 2068 Trichothiodystrophy 1, photosensitive; Xeroderma pigmentosum, group D AR Pediatric Allelic with Cerebrooculofacioskeletal syndrome 2 (AR) Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic Allergy/Immunology/Infectious; Dermatologic; Oncologic In Trichothiodystrophy, individuals may be at high risk for skin cancer, and preventive measures may be beneficial; Frequent infections have been reported, and prophylaxis and early and aggressive treatment of infections may be beneficial; In XP, skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance can be beneficial 2189905; 1372108; 7802014; 8783572; 11709541; 11443545; 21959366; 20301571 ERCC3 3435 2071 Xeroderma pigmentosum, complementation group B; Trichothiodystrophy 2, photosensitive AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic Allergy/Immunology/Infectious; Dermatologic; Oncologic In Trichothiodystrophy, individuals may be at high risk for skin cancer, and preventive measures may be beneficial; Frequent infections have been reported, and prophylaxis and early and aggressive treatment of infections may be beneficial; In XP, skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance (primarily related to skin manifestations, as well as other sequelae) can be beneficial 4811796; 6185841; 2189905; 2167179; 8783572; 9012405; 16947863; 20301571 ERCC4 3436 2072 Fanconi anemia, complementation group Q; Xeroderma pigmentosum, complementation group F AR Pediatric Allelic with XFE progeroid syndrome (AR) Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Dermatologic; Hematologic; Oncologic Fanconi anemia can involve multiple congenital anomalies In XP, skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance (primarily related to skin manifestations, as well as other sequelae) can be beneficial; In Fanconi anemia, specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 3834095; 3372781; 2696553; 8427828; 10447254; 17183314; 20301571; 23623386 ERCC5 3437 2073 Xeroderma pigmentosum, complementation group G; Xeroderma pigmentosum, complementation group G/Cockayne syndrome AR Pediatric Allelic with Cerebrooculofacioskeletal syndrome 3 (AR) Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic Dermatologic; Oncologic Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance for dermatologic manifestations can be beneficial 492197; 11219864; 3620347; 8317483; 8818951; 9096355; 11228268; 11841555; 20301571; 24700531 ERCC6 3438 2074 Premature ovarian failure 11; Xeroderma Pigmentosum-Cockayne Syndrome; De Sanctis-Cacchione syndrome AD/AR Pediatric Allelic with Cerebrooculofacioskeletal syndrome 1 (AR); Cockayne syndrome B (AR); UV-sensitive syndrome (AR), in which individuals have sun senstivity, but are not reported to have skin cancer Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Obstetric; Oncologic; Ophthalmologic Audiologic/Otolaryngologic; Dermatologic; Gastrointestinal; Obstetric; Oncologic Individuals with Cockayne syndrome without skin sensitivity have been described In Cockayne syndrome, periodic surveillance for manifestations affecting the audiologic, ophthalmologic, hepatic, and other systems can be beneficial; Metronidazole should be avoided due to concerns of hepatic failure; Some individuals with Xeroderma Pigmentosum-Cockayne Syndromecan have predisposition to skin cancer; Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance for dermatologic manifestations can be beneficial; For Premature ovarian failure, genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency 14246158; 5560051; 4211825; 4431498; 7264357; 3545087; 1372469; 9443879; 9777763; 10196384; 10767341; 10739753; 15486090; 18446857; 18628313;20456449; 20301571; 22466610; 26204423; 26218421 ERCC6L2 26922 375748 Bone marrow failure syndrome 2 AR Pediatric Hematologic; Neurologic Hematologic Individuals have been described with tri-lineage bone marrow failure, and awareness may allow prompt recognition and management related to hematologic (eg, anemia) and infectious sequelae 24507776 ERCC8 3439 1161 Cockayne syndrome A AR Pediatric Allelic with UV-sensitive syndrome 2 (AR) Dermatologic; Musculoskeletal; Neurologic Neurologic UV-sensitive syndrome 2 has not been described as associated with increased risk of skin cancer In Cockayne syndrome, some neurological manifestations have been reported as responding to treatment with carbidopa-levodopa 14783428; 1308368; 7664335; 9443879; 11185579; 14661080; 15744458; 16865293; 18695064;19329487; 19894250; 21108394; 26218421 ERF 3444 2077 Chitayat syndrome AD Pediatric Allelic with Craniosynostosis 4 (AD) Craniofacial; Musculoskeletal; Neurologic; Pulmonary Pulmonary Among other features, Chitayat syndrome can include neonatal respiratory distress requiring ventilatory support, and awareness may allow early recognition and management 8418638; 23354439; 26097063; 27738187 ERGIC1 29205 57222 Arthrogryposis multiplex congenita 2, neurogenic type AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5491443; 28317099 ERLIN1 16947 10613 Spastic paraplegia 62, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24482476 ERLIN2 1356 11160 Spastic paraplegia 18, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21330303; 23109145 ERMAP 15743 114625 Blood group, Scianna system; Blood group, Radin BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 7998072; 12393480; 15954808 ERMARD 21056 55780 Periventricular nodular heterotopia 6 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24056535 ESAM 17474 90952 Schizophrenia AD N/A N/A Neurologic General Evidence or clinical applicability is unclear 21822266 ESCO2 27230 157570 Roberts-SC phocomelia syndrome; Juberg-Hayward syndrome AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Individuals with Roberts-SC phocomelia syndrome have been described developing complications such as cardiovascular complications Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7067161; 3740099; 1642282; 16380922; 15821733; 18411254; 19574259; 32255174; 32977150 ESPN 13281 83715 Deafness, autosomal dominant, without vestibular involvement; Deafness, autosomal recessive 36, with or without vestibular involvement; Usher syndrome, type 1M AD/AR Pediatric Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 15286153; 15930085; 18973245; 29572253 ESR1 3467 2099 Estrogen resistance AR N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8090165; 8961262; 9396482; 18505767; 23841731 ESR2 3468 2100 Ovarian dysgenesis 8 AR Pediatric Endocrine; Obstetric Endocrine Individuals can present with features such as primary amenorrhea, and osteoporosis, and medical management (eg, with estrogen therapy) has been described as beneficial 30113650 ESRP1 25966 54845 Deafness, autosomal recessive 109 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 29107558 ESRRB 3473 2103 Deafness, autosomal recessive 35 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12529709; 18179891; 26805784 ETFA 3481 2108 Multiple acyl-CoA dehydrogenase deficiency (Glutaric aciduria IIA) AR Pediatric Biochemical; Gastrointestinal; Musculoskeletal; Neurologic; Renal Biochemical Dietary measures (fasting avoidance and low-fat diet, as well as supplementation, such as with riboflavin and carnitine) may be beneficial 7145508; 8771170; 1882842; 1430199; 12815589; 18289905; 20736750; 22231380 ETFB 3482 2109 Multiple acyl-CoA dehydrogenase deficiency (Glutaric aciduria IIB) AR Pediatric Biochemical; Gastrointestinal; Musculoskeletal; Neurologic; Renal Biochemical Dietary measures (fasting avoidance and low-fat diet, as well as supplementation, such as with riboflavin and carnitine) may be beneficial 7145508; 8771170; 7912128; 12706375; 12815589; 18289905; 22231380 ETFDH 3483 2110 Multiple acyl-CoA dehydrogenase deficiency (Glutaric aciduria IIC) AR Pediatric Biochemical; Gastrointestinal; Musculoskeletal; Neurologic; Renal Biochemical Dietary measures (fasting avoidance and low-fat diet, as well as supplementation, such as with riboflavin and carnitine) may be beneficial 7145508; 8771170; 12815589; 16527485; 17412732; 17584774; 18289905; 19208393; 19249206; 19758981; 19783111; 20138856; 20370797; 20837308; 21088898; 21616504; 21907580; 22041377; 22231380; 22664151; 23106979; 23893693 ETHE1 23287 23474 Ethylmalonic encephalopathy AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Neurologic Biochemical The condition can manifest with features including neurological impairment and chronic diarrhea, and dietary (eg, with restriction of branched amino acids, fatty acids, and methionine) and medical treatment (eg, with metronidazole and N-acetylcysteine) has been reported as having clinical benefit 14732903; 18593870; 20528888; 20657580; 20978941; 21472225; 22584649; 22805253 ETV6 3495 2120 Thrombocytopenia 5 AD Pediatric Hematologic; Oncologic Hematologic; Oncologic Individuals have bleeding tendency, and awareness may allow preventive measures and early management of bleeding episodes; Individuals are at risk of hematologic malignancy (other other cancer types have also been reported), and awareness may allow early diagnosis and management; HSCT has been described 25581430; 25807284 EVC 3497 2121 Ellis-van Creveld syndrome; Weyers acrofacial dysostosis AD/AR N/A N/A Cardiovascular; Craniofacial; Dental; Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7628126; 10700184; 17024374; 18454448; 18947413; 19744229; 20184732; 23220543 EVC2 19747 132884 Ellis-van Creveld syndrome; Weyers acrodental dysostosis AD/AR N/A N/A Cardiovascular; Craniofacial; Dental; Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12468274; 12571802; 16404586; 17024374; 20184732; 21815252; 22406498; 23026208; 23220543; 23276573 EXOC2 24968 55770 Neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32639540 EXOC6B 17085 23233 Spondyloepimetaphyseal dysplasia with joint laxity 3 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26669664; 30284759 EXOSC1 17286 51013 Pontocerebellar hypoplasia, type 1F AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33463720 EXOSC2 17097 23404 Short stature, hearing loss, retinitis pigmentosa, and distinctive facies AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 26843489 EXOSC3 17944 51010 Pontocerebellar hypoplasia type 1B AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11020648; 12731647; 22544365; 24524299; 25149867 EXOSC8 17035 11340 Pontocerebellar hypoplasia, type 1C AR N/A N/A Audiologic/Otolaryngologic; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24989451 EXOSC9 9137 5393 Pontocerebellar hypoplasia, type 1D AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29727687; 30690203 EXPH5 30578 23086 Epidermolysis bullosa, nonspecific, autosomal recessive AR N/A N/A Dermatologic General Though appropriate skin care may be beneficial, it is unclear if early (genetic) diagnosis would be additionally advantageous Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23176819 EXT1 3512 2131 Exostoses, multiple, type 1; Chondrosarcoma AD Pediatric Musculoskeletal; Oncologic Oncologic Though onset of malignancy is typically described in adulthood, some individuals have been affected at an earlier age; Germline variants have also been implicated in chondrosarcoma In Exostoses, multiple, type 1, though data regarding the efficacy of surveillance are lacking, individuals are at risk for the (relatively infrequent) development of malignant change of exostoses, and awareness may allow early detection and management; In Chondrosarcoma, individuals may be at risk of chondrosarcoma, and awareness may allow early diagnosis and management 7550340; 8981950; 9326317; 9521425; 9463333; 10679937; 11432960; 11170095; 15253765; 16879194; 19344451; 20301413; 22258776; 23629877; 23770606 EXT2 3513 2132 Exostoses, multiple, type 2 AD Pediatric Allelic with Seizures, scoliosis, and macrocephaly syndrome (AR) Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Oncologic Oncologic Though onset of malignancy is typically described in adulthood, some individuals have been affected at an earlier age; Germline variants have also been implicated in chondrosarcoma Though data regarding the efficacy of surveillance are lacking, individuals are at risk for the (relatively infrequent) development of malignant change of exostoses, and awareness may allow early detection and management 7726168; 8782816; 8894688; 9326317; 9463333; 10679937; 11432960; 16879194; 19344451; 20301413; 22258776; 23629877; 23770606; 26246518 EXTL3 3518 2137 Immunoskeletal dysplasia with neurodevelopmental abnormalities AR Pediatric Allergy/Immunology/Infectious; Musculoskeletal; Neurologic Allergy/Immunology/Infectious The condition can include severe combined immunodeficiency, and awareness may allow preventive measures and early and aggressive treatment of infections 28148688; 28132690 EYA1 3519 2138 Branchiootic syndrome 1; Branchiootorenal syndrome 1, with or without cataracts; Otofaciocervical syndrome 1 AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic; Renal Audiologic/Otolaryngologic; Renal Individuals can have characteristic aural anomalies, but these may not be readily ascertained; In BOR, surveillance and treatment/prophylaxis related to renal manifestations can be beneficial Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In BOR, surveillance and treatment/prophylaxis related to vesicoureteral reflux can be beneficial 9020840; 9359046; 10991693; 11409867; 12404110; 15146463; 16441263; 16691597; 18177466; 18220287; 20301554; 19206155 EYA4 3522 2070 Cardiomyopathy, dilated, 1J AD Adult Allelic with Deafness, autosomal dominant 10 (AD) Audiologic/Otolaryngologic; Cardiovascular Cardiovascular The condition may also include childhood-onset sensorineural hearing loss Related to cardiomyopathy, preventive measures and medical management may be helpful to help decrease morbidity 10769282; 10982027; 11159937; 15735644; 17568404; 17567890 EYS 21555 346007 Retitinis pigmentosa 25 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18836446; 18976725; 21069908; 21179430; 21519034; 22277662; 22302105; 22363543 EZH2 3527 2146 Weaver syndrome AD N/A N/A Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4366187; 22177091 F10 3528 2159 Factor X deficiency AR Pediatric Hematologic Hematologic; Pharmacogenomic Individuals can suffer from bleeding diatheses of varying severity, and preventive measures related to bleeding episodes can be beneficial, including in special circumstances such as pregnancy; Precautions should be taken related to certain agents that may provoke/worsen bleeding risk 5450692; 4989292; 4995085; 3732313; 8192155; 3408671; 2567188; 2790181; 1985698; 1997381; 9695984; 10746568; 12028042; 22151249; 22460599; 22506295 F11 3529 2160 Factor XI deficiency AD/AR Pediatric Hematologic Hematologic; Pharmacogenomic Heterozygotes may have manifestations that warrant interventions Individuals may be at risk of bleeding (eg, following surgery or with injury, and during delivery), and prophylaxis and preventive measures (eg, including avoidance of aspirin) and prompt treatment (eg, with fresh frozen plasma) may be beneficial, including considerations prior to/during pregnancy; Antifibrinolytic therapy may be beneficial in females with menorrhagia 3871646; 2439152; 3553944; 2813350; 8800510; 18434707; 18160615; 19598070; 19367158; 19049995; 21577094; 21699628; 22624777; 22726099 F12 3530 2161 Angioedema, hereditary, type III AD/AR Pediatric Allelic with Factor XII deficiency (AD) (in which, though the evidence is mixed, individuals do not appear to have a predisposition to severe bleeding diatheses or thromboembolic complications) Allergy/Immunology/Infectious; Hematologic Allergy/Immunology/Infectious; Pharmacogenomic Attacks, which can include potentially life-threatening upper airway obstruction, can be precipitated by high estrogen levels (eg, pregnancy, OCPs) 14490552; 4968868; 5432188; 6348471; 2882793; 2110579; 1905067; 8419231; 7947293; 11069485; 15306750; 15013868; 15678272; 19477491; 20729721; 20667118; 20695852; 21849258; 20729721; 21297451; 22043782; 22801442; 22197449; 22729959 F13A1 3531 2162 Factor XIIIA deficiency AR Pediatric Hematologic Hematologic; Pharmacogenomic Individuals have increased bleeding and poor wound healing; awareness and management of bleeding risk in certain situations (eg, obstetric event or surgery) may decrease morbidity; Precautions should be taken related to certain agents that may provoke/worsen bleeding risk 1644910; 8025280; 7727776; 8547636; 9459313; 10365735; 12072871; 12456499; 17393027; 19438481; 20108427; 21512576 F13B 3534 2165 Factor XIIIB deficiency AR Pediatric Hematologic Hematologic; Pharmacogenomic Individuals have increased bleeding and poor wound healing; awareness and management of bleeding risk in certain situations (eg, obstetric event or surgery) may decrease morbidity; Precautions should be taken related to certain agents that may provoke/worsen bleeding risk 2334637; 8324218; 11313256; 20331752; 21640452 F2 3535 2147 Prothrombin deficiency, congenital; Thrombophilia due to thrombin defect AD/AR Pediatric Hematologic Hematologic; Pharmacogenomic Variants in F2 may interact with variants in other genes, such as F5, to result in susceptibility to hematologic manifestations; Heterozygous variants associated with Prothrombin deficiency have been described as demonstrating increased bleeding tendency, such as post-dental or surgical bleeding In individuals with Thrombophilia due to thrombin defect , as relates to the specific 20210G-A variant, variant carriers may benefit from preventive measures and/or other interventions when other risk factors are present or in symptomatic disease; In AR forms of disease (Prothrombin deficiency), surveillance and prompt treatment of bleeding diatheses may reduce morbidity; Precautions should be taken related to certain agents that may provoke/worsen bleeding risk 4489469; 7740448; 8916933; 9869612; 10233438; 10477778; 11734673; 10666427; 11167765; 11506076; 15534175; 19598065; 22716977 F5 3542 2153 Thrombophilia due to activated protein C resistance; Factor V deficiency AD/AR Pediatric Hematologic Hematologic; Pharmacogenomic Variants in F5 may interact with variants in other genes, such as F2 and MTHFR, to result in susceptibility to hematologic manifestations In Thrombophilia due to activated protein C resistance, surveillance and treatment (including preventive measures in some individuals) may reduce morbidity; The condition may result in recurrent pregnancy loss, and awareness may help management of pregnancy; Precautions should be taken regarding the avoidance of certain medications (eg, estrogen-containing OCPs); Individuals with Factor V deficiency can suffer from bleeding diatheses of varying severity, and preventive measures, as well as prompt treatment (eg, with fresh frozen plasma or platelet transfusion in instances of severe bleeding) related to bleeding episodes can be beneficial 20293060; 13194849; 13575936; 1239529; 694421; 6348091; 6479988; 8430067; 7803250; 8108421; 8164741; 7910348; 7969326; 8049422; 7911872; 7911873; 7989612; 7586244; 7877648; 8616100; 8627449; 8639453; 8815565; 9207293; 9245936; 9010145; 9372726; 9518910; 9577282; 9877047; 9576178; 9846775; 9734642; 9459326; 9462312; 9488630; 9454742; 10233438; 10477778; 10066036; 10328130; 9878639; 10507841; 10666427; 11001884; 11018168; 11167765; 10943572; 11532625; 11435304; 11781258; 11859850; 12138364; 12393490; 12393635; 14617013; 15534175; 15293282; 14673478; 14996674; 16113779; 16551553; 16707754; 16606808; 19531787; 21292261; 21320286; 21730834; 21777354; 22251029; 22758216; 22888854; 22990475; 23034579 F7 3544 2155 Factor VII deficiency AR Pediatric Hematologic Hematologic; Pharmacogenomic Individuals can suffer from bleeding diatheses of varying severity, and preventive measures and prompt treatment (including with factor replacement therapy) related to bleeding episodes can be beneficial; Precautions should be taken related to certain agents that may provoke/worsen bleeding risk 7919338; 7981691; 8652821; 8883260; 9680360; 11091194; 10984565; 11129332; 10862079; 11225604; 11139238; 11260055; 12181036; 11529858; 22188821; 22327818; 22356641; 22628013; 22684392; 22845882; 22873696; 22974900 F8 3546 2157 Hemophilia A XL Pediatric Hematologic Hematologic; Pharmacogenomic Plasma-derived factor VIII concentrate and/or desmopressin can be used to treat/prevent bleeding, and gene therapy has been described as beneficial; Other considerations may be beneficial in specific circumstances, such as in postpartum females; Certain circumstances should be avoided or need to be specifically managed, such as circumcision, high-risk activities, and medications such as aspirin 13739554; 2987704; 3012775; 3035554; 3097553; 3338800; 3131627; 2833855; 2835904; 3139545; 1688823; 2123300; 1357455; 8275087; 8281136; 8259143; 7662970; 3893256; 8644728; 8968748; 9042915; 11023529; 11396445; 11857744; 12907007; 16786531; 16551972; 18691168; 18217193; 20301578; 21056901; 22507546; 22621702; 22639879; 22866674; 23005041; 23025325; 23047359; 23067060; 29224506 F9 3551 2158 Hemophilia B; Thrombophilia, X-linked, due to factor IX defect; Warfarin sensitivity, X-linked XL Pediatric Hematologic Hematologic; Pharmacogenomic In Hemophilia B, recombinant or plasma-derived factor IX concentrate can be effective for prevention/treatment of bleeding episodes, and gene therapy has been described as beneficial; Other considerations may be beneficial in specific circumstances, such as in postpartum females; Certain circumstances should be avoided or need to be specifically managed, such as circumcision, high-risk activities, and medications such as aspirin; In X-linked thrombophilia, preventive measures related to thrombophilia, as well as early recognition and treatment of manifestations such as deep venous thromboses, may reduce morbidity 14920537; 12997790; 4163943; 4972271; 5781711; 5450691; 734633; 7062952; 6142993; 3001143; 2907054; 3219291; 2841226; 2570235; 1768766; 1873221; 1601420; 8392713; 8352232; 8096443; 8304338; 8594556; 8833911; 9016521; 9233593; 10845896; 11122385; 11328285; 18349091; 18624978; 19251637; 19815722; 19846852; 20301668; 21056901; 29211678 FA2H 21197 79152 Spastic paraplegia 35, autosomal recessive AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18463364; 19068277; 20104589; 20853438; 22146942; 22925154; 23745665; 24359114 FAAHP1 50679 729041 Pain sensitivity quantitative trait locus 1 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30929760 FADD 3573 8772 Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovascular malformations AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Neurologic Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Patients suffer from stereotypical episodes of fever, liver dyfunction, and encephalopathy, which may be severe and precipitated by viral infections; Other findings, such as cardiovascular malformations, and fucntional hyposplenism, have been described 21109225 FAH 3579 2184 Tyrosinemia, type I AR Pediatric Biochemical; Gastrointestinal; Musculoskeletal; Oncologic; Renal Biochemical; Oncologic Dietary (controlled intake of phenylalanine and tyrosine) and medical (eg, nitsinone) treatment can be beneficial, and may reduce risks related to manifestations (eg, hepatocellular carcinoma) that are part of the natural history in untreated individuals; Some individuals require liver transplantation 14085846; 14271358; 6016174; 2536631; 2153931; 2378357; 1383656; 1440864; 8028615; 7977370; 7603784; 8829657; 9101289; 9728331; 10603099; 11575602; 12203990; 15759101; 20301688; 22554029 FAM111A 24725 63901 Kenny-Caffey syndrome, type 2 AD Pediatric Craniofacial; Endocrine; Musculoskeletal; Ophthalmologic Endocrine Among other findings, individuals may manifest with primary hypoparathyroidism with hypocalcemia (which can be life-threatening), and awareness may allow early management 23684011 FAM111B 24200 374393 Poikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonary fibrosis AD N/A N/A Dermatologic; Musculoskeletal; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24268661 FAM126A 24587 84668 Leukodystrophy, hypomyelinating, 5 AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16951682 FAM149B1 29162 317662 Joubert syndrome 36 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30905400 FAM161A 25808 84140 Retitinis pigmentosa 28 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10507729; 20705279; 20705278 FAM20A 23015 54757 Amelogenesis imperfecta, type IG (Enamel-renal syndrome) AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18597613; 21549343; 21990045; 23434854; 24196488 FAM20C 22140 56975 Hypophosphatemia, hyperphosphaturia, dental anomalies, intracerebral calcifications and osteosclerosis (Raine syndrome) AR Pediatric Craniofacial; Dental; Musculoskeletal; Neurologic; Renal Renal The condition includes hypophosphatemia an urinary phosphate wasting, and medical management (with oral phosphate supplements) has been described, and may be beneficial 2614802; 2020859; 12868469; 14564151; 17924334; 19250384; 20825432; 23325605 FAM50A 18786 9130 Intellectual disability disorder, X-linked, syndrome, Armfield type XL N/A N/A Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10398235; 32703943 FAM83H 24797 286077 Amelogenesis imperfecta, type IIIA AD N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18252228; 18484629; 19220331; 19407157; 21702852; 23355523 FAN1 29170 22909 Interstitial nephritis, karyomegalic AR N/A N/A Gastrointestinal; Renal General Individuals may suffer renal failure, and renal transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7847351; 8546134; 16678356; 17304531; 22772369 FANCA 3582 2175 Fanconi anemia, complementation group A AR Pediatric Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 13826667; 6338978; 2571931; 1536187; 1521091; 8502512; 8081006; 8781414; 9371798; 10094191; 11389461; 14504102; 14605744; 17105750; 20301575; 20507306; 21273304; 22480464; 22950077; 23067021; 23898106; 23973728 FANCB 3583 2187 Fanconi anemia,complementation group B XL Pediatric Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 15502827; 16679491; 20301575; 21910217; 22052692 FANCC 3584 2176 Fanconi anemia, complementation group C AR Pediatric Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 1574115; 9272737; 10431244; 20301575; 22160080; 22701786; 23028338 FANCD2 3585 2177 Fanconi anemia, complementation group D2 AR Pediatric Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 17436244; 20301575; 22720145; 23285130 FANCE 3586 2178 Fanconi anemia, complementation group E AR Pediatric Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 11001585; 17924555; 20301575; 22778927 FANCF 3587 2188 Fanconia anemia, complementation group F AR Pediatric Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 10615118; 20301575 FANCG 3588 2189 Fanconi anemia, complementation group G AR Pediatric Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 9806548; 20301575 FANCI 25568 55215 Fanconi anemia, complementation group I AR Pediatric Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 14630800; 17452773; 17460694; 17412408; 20301575; 21568838 FANCL 20748 55120 Fanconi anemia, complementation group L AR Pediatric Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 12973351; 20301575; 22720145; 25754594 FANCM 23168 57697 Premature ovarian failure 15 AR Pediatric Allelic with Spermatogenic failure 28 (AR) Endocrine; Genitourinary; Obstetric Obstetric Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management In Premature ovarian failure, genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency 16116422; 20301575; 28837162 FAR1 26222 84188 Cataracts, spastic paraparesis, and speech delay; Peroxisomal fatty acyl-CoA reductase 1 disorder AD/AR N/A N/A Biochemical; Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26220973; 33239752 FARS2 21062 10667 Combined oxidative phosphorylation deficiency 14; Spastic paraplegia 77, autosomal recessive AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22499341; 22833457; 26553276 FARSA 3592 2193 Rajab interstitial lung disease with brain calcifications 2 AR Pediatric Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary Endocrine; Pulmonary An individual has been described with endocrine manifestations, including panhypopituitarism and hypothyroidism, and awareness may allow early diagnosis and medical management (eg, with hormone replacement therapy); The condition can include severe lung disease, and awareness may allow prompt diagnosis and management; 31355908 FARSB 17800 10056 Rajab interstitial lung disease with brain calcifications AR Pediatric Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary; Renal Cardiovascular; Pulmonary The condition can include vascular aneurysms as well as severe lung disease, and awareness may allow prompt diagnosis and management; lung transplant has been described 29573043 FAS 11920 355 Autoimmune lymphoproliferative syndrome, type IA AD/AR Pediatric Allergy/Immunology/Infectious; Hematologic; Oncologic; Renal Allergy/Immunology/Infectious; Oncologic Lymphoproliferation can be suppressed with medications such as corticosteroids, cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil; BMT/HSCT the only curative treatment for ALPS, has to date mostly been reported in patients with severe clinical findings; Surveillance for manifestations of lymphoproliferation and autoimmunity, and specialized imaging studies to detect malignant transformation may be beneficial 4165068; 1386609; 7540117; 8929361; 10709732; 15459302; 20301287 FASLG 11936 356 Autoimmune lymphoproliferative syndrome, type IB AD Pediatric Allergy/Immunology/Infectious; Hematologic; Oncologic; Renal Allergy/Immunology/Infectious; Oncologic Biallelic variants have been described as resulting in more severe presentations, including as relates to autoimmunity and lymphoproliferation Lymphoproliferation can be suppressed with medications such as corticosteroids, cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil; BMT/HSCT the only curative treatment for ALPS, has to date mostly been reported in patients with severe clinical findings; Surveillance for manifestations of lymphoproliferation and autoimmunity, and specialized imaging studies to detect malignant transformation may be beneficial 8787672; 15004557; 16627752; 17605793; 20301287 FASTKD2 29160 22868 Mitochondrial complex IV deficiency AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18771761; 28499982; 31944455 FAT2 3596 2196 Spinocerebellar ataxia 45 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29053796 FAT4 23109 79633 Hennekam lymphangiectasia-lymphedema syndrome 2 AR Pediatric Allelic with Van Maldergem syndrome 2 (AR) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Dental; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Pulmonary; Renal Allergy/Immunology/Infectious; Gastrointestinal The condition can include manifestations such as protein-losing enteropathy (which may be refractory), as well as features for which treatment can be beneficial, such as infectious sequelae, for which early and aggressive treatment may be beneficial 2624276; 22469822; 22473091; 24056717; 24913602 FBLN1 3600 2192 Synpolydactyly 2 AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; In Cutis laxa, individuals can have cardiac manifestations such as supravalvular aortic stenosis, but the condition should be recognizable 8831136; 11836357 FBLN5 3602 10516 Neuropathy, hereditary, with or witout age-related macular degeneration; Macular degeneration, age-related, 3; Cutis laxa, autosomal dominant 2; Cutis laxa, autosomal recessive, type IA AD/AR N/A N/A Dermatologic; Cardiovascular; Gastrointestinal; Genitourinary; Neurologic; Ophthalmologic; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12189163; 12618961; 15269314; 20301756; 22829427 FBN1 3603 2200 Marfan syndrome; MASS syndrome; Shprintzen-Goldberg syndrome; Marfanoid-progeroid-lipodystrophy syndrome; Ectopia lentis 1, familial; Geleophysic dysplasia 2; Weill-Marchesani syndrome 2 AD Pediatric Allelic with Acromicric dysplasia (AD); Stiff skin syndrome (AD) Cardiovascular; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary Cardiovascular; Musculoskeletal; Ophthalmologic; Pharmacogenomic; Pulmonary Medications that reduce aortic wall hemodynamic stress (eg, beta blockers) have been shown to be effective; Afterload-reducing agents can improve cardiovascular function in CHF; Surgical aortic repair is indicated depending on parameters such as size and rate of change of aorta; Other issues also require attention and may benefit from regular surveillance, such as those involving ophthalomologic, pulmonary, and skeletal complications; Certain agents and circumstances should be avoided, including activities that impose cardiovascular or musculoskeletal risk, as well as agents such as decongestants, caffeine; LASIK is typically contraindicated; Geleophysic dysplasia may frequently be clinically recognizable, but individuals can have cardiovascular manifestations such as progressive cardiac valve thickening necessitating surgical interventions very early in childhood, and early diagnosis may be beneficial to allow early treatment; In Weill-Marchesani syndrome, awareness of the risk of certain ophthalmological complications (including glaucoma) can allow prompt awareness and treatment 1157278; 370588; 6182156; 2938007; 3189335; 2322060; 1852208; 2337033; 1864149; 1301946; 1569206; 1736263; 1542340; 8406497; 7802039; 7573130; 8152445; 8863159; 8733052; 8790089; 8563763; 9150726; 9761390; 10489951; 10219065; 11256662; 11700157; 12446365; 11845856; 11826022; 12525539; 14598350; 15054843; 15731757; 15517394; 16596670; 16202954; 17366579; 18579813; 19996017; 19353630; 20375004; 20301510; 20301776; 20886638; 20979188; 21063442; 21594992; 21594993; 21683322; 21883168; 21932315; 22034023; 22461464; 22736615; 22876116; 22950452; 24613577 FBN2 3604 2201 Congenital contractural arachnodactyly (Beals syndrome) AD Pediatric Allelic with Macular degeneration, early onset (AD) Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Ophthalmologic Cardiovascular The condition may be clinically recognizable in most individuals, but individuals may have cardiovascular manifestations including aortic root dilatation, and surveillance and early interventions may reduce morbidity and mortality 7493032; 7633409; 8900230; 9106527; 9714438; 10797416; 11754102; 16531736; 20301560; 24899048 FBP1 3606 2203 Fructose-1,6-bisphosphatase deficiency AR Pediatric Biochemical Biochemical The condition may be lethal in the perinatal period, but prompt recognition and treatment of lactic acidosis and hypoglycemia (eg, with IV/oral glucose, sodium bicarbonate) can be effective 4193749; 4335192; 4341454; 4341015; 175754; 2347355; 1995492; 9382095; 12126934; 17705024; 19259699; 20096900; 22158280 FBXL3 13599 26224 Intellectual developmental disorder with short stature, facial anomalies, and speech defects AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11477608; 30481285 FBXL4 13601 26235 Mitochondrial DNA depletion syndrome 13 AR N/A N/A Biochemical; Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23993193; 23993194 FBXO11 13590 80204 Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27620904; 29796876; 30057029 FBXO31 16510 79791 Mental retardation 45, autosomal recessive AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24623383 FBXO38 28844 81545 Neuronopathy, distal hereditary motor, type IID AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7723953; 24207122 FBXO7 13586 25793 Parkinson disease 15, autosomal recessive AR Pediatric Neurologic Neurologic Individuals have been described with levodopa response 18513678; 19038853; 23318512 FBXW11 13607 23291 Neurodevelopmental, jaw, eye, and digital syndrome AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31402090 FCGR3A 3619 2214 Immunodeficiency 20 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described as affected by early-onset severe herpes viral infections (eg, EBV, HPV), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 8608639; 8874200; 23006327 FCHO1 29002 23149 Immunodeficiency 76" AR Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic Individuals have been described as affected by early-onset and severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Oncologic complications have been described, and awareness may alow early diagnosis and management; HSCT has been described 30822429; 32098969 FCMTE2 37159 554188 Epilepsy, myoclonic, adult familial, 2 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11701600; 24114805 FCN3 3625 8547 Immunodeficiency due to Ficolin 3 deficiency AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Sequelae have been described as including frequent and severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 19535802 FCSK 29500 197258 Congenital disorder of glycosylation with defective fucosylation 2 AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30503518 FDFT1 3629 2222 Squalene synthase deficiency AR N/A N/A Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29909962 FDPS 3631 2224 Porokeratosis 9, multiple types AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26202976 FDX2 30546 112812 Mitochondrial myopathy, episodic, with or without optic atrophy and reversible leukoencephalopathy AR Pediatric Biochemical; Musculoskeletal; Neurologic; Renal Musculoskeletal; Renal Among other features, the condition can include rhabdomyolysis, and awareness may allow medical management 24281368;30010796 FDXR 3642 2232 Auditory neuropathy and optic atrophy AR N/A N/A Audiologic/Otolaryngologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28965846 FECH 3647 2235 Protoporphyria, erythropoietic 1 AD/AR Pediatric Dermatologic; Gastrointestinal; Hematologic Dermatologic; Gastrointestinal The inheritance pattern can be complex, and can involve a deleterious variant in trans with a "low-normal" polymorphism (sometimes termed "pseudodominant" inheritance), as well as homozygosity/compound heterozygosity for deleterious variants; Agents associated with hepatic dysfunction should be avoided While the only manifestation in many individuals is photosensitivity (for which light avoidance and possible medical treatment, such as with alpha-melanocyte-stimulating hormone analog, can be beneficial), some individuals can have severe liver sequelae, and surveillance and medical treatment (eg, with cholestyramine) can be beneficial; BMT and liver transplantation may be necessary 14072370; 5835322; 14338805; 6019665; 5536249; 1138541; 1251847; 911406; 3805002; 6742776; 2384686; 1755842; 8571955; 8601739; 9649563; 9585598; 11039124; 11753383; 12601550; 16385445; 17875872; 19144952; 18787536; 19744342; 20857522; 21659066; 22971305; 23016163; 23323258; 23600449 FERMT1 15889 55612 Kindler syndrome AR Adult Dermatologic; Oncologic Dermatologic; Oncologic Individuals have an increased risk of squamous cell carcinoma and surveillance for premalignant keratoses/early malignancy may allow early diagnosis and treatment 13149722; 8910840; 9301588; 10809978; 12472544; 12668616; 12789646; 17460733; 17854379; 17916195; 17989907; 18410424; 18835760; 19292718; 19945624; 21336475; 21936020 FERMT3 23151 83706 Leukocyte adhesion deficiency, type III AR Pediatric Allergy/Immunology/Infectious; Hematologic Allergy/Immunology/Infectious; Hematologic Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals may have hematologic anomalies, and treatment (which may include RBC and platelet transfusions) may be indicated; BMT has been described 9312170; 12595312; 17185466; 19234460; 19064721; 20357244; 21441448 FEZF1 22788 389549 Hypogonadotropic hypogonadism 22 with or without anosmia AR Pediatric Endocrine; Neurologic Endocrine In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 25192046 FGA 3661 2243 Afibrinogenemia, congenital; Dysfibrinogenemia, congenital; Familial visceral amyloidosis AD/AR Pediatric Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Renal Cardiovascular; Gastrointestinal; Hematologic; Pharmacogenomic Individuals with afibrinogenemia/dysfibrinogenemia are at risk of a variety of bleeding diatheses; Preventive or treatment-based (eg, with fibrinogen in the case of congenital afibrinogenemia) measures may be beneficial; Individuals with Familial amyloidosis may be at risk of cardiovascular complications, including arrhythmia, and surveillance may allow prompt detection and management; The treatment of amyloidosis differs depending on the genetic cause (genetic diagnosis may additionally help avoid relatively high-risk treatment regimens), and in fibrinogen-related amyloidosis, liver transplantation may be beneficial 5645286; 7298640; 6191801; 4052020; 3726812; 3618591; 3590111; 3345340; 2133234; 1675636; 2070049; 1391954; 1634621; 8097946; 8140431; 8473507; 8113408; 8675656; 8639778; 9389696; 9916133; 10891444; 10910940; 11739173; 11159525; 12050338; 12358944; 14615374; 15489905; 16362348; 18500534; 20806111; 21245743; 22732251; 22795623 FGB 3662 2244 Afibrinogenemia, congenital; Dysfibrinogenemia, congenital; Hypodysfibrinogenemia, congenital AD/AR Pediatric Hematologic Hematologic Individuals with afibrinogenemia/dysfibrinogenemia are at risk of a variety of bleeding diatheses; Preventive or treatment-based (eg, with fibrinogen in the case of congenital afibrinogenemia) may be beneficial 3156856; 2885451; 3388290; 2018836; 1565641; 1634610; 9185528; 10666208; 11468164; 11425767; 12393540; 15070683; 18853456; 21301788; 22955321 FGD1 3663 2245 Aarskog-Scott syndrome (Mental retardation, X-linked syndromic 16) XL N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5504078; 5173168; 7954831; 10930571; 11093277; 15809997; 17152066; 17847065; 19110080; 20082460; 21654724; 21739585; 22876573 FGD4 19125 121512 Charcot-Marie-Tooth disease, type 4H AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15744041; 17564959; 17564972; 19221294; 19332693; 20301641; 21840889; 22734899 FGF10 3666 2255 Lacrimoauriculodentodigital syndrome AD Pediatric Allelic with Aplasia of lacrimal and salivary glands (AD) Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 15654336; 16501574; 16630169; 17213838 FGF12 3668 2257 Developmental and epileptic encephalopathy 47 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27164707 FGF13 3670 2258 Developmental and epileptic encephalopathy 90 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33245860 FGF14 3671 2259 Spinocerebellar ataxia 27 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12489043; 15470364; 21600715 FGF16 3672 8823 Metacarpal 4-5 fusion XL N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23709756; 24878828 FGF17 3673 8822 Hypogonadotropic hypogonadism 20, with or without anosmia AD/Multigenic Pediatric Craniofacial; Endocrine; Musculoskeletal; Neurologic Endocrine Relatively complex genetic models of disease have been described (eg, involving variants in other FGF8-network-associated genes) In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 6881209; 23643382 FGF20 3677 26281 Renal hypodysplasia/aplasia 2 AR N/A N/A Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22698282 FGF23 3680 8074 Hypophosphatemic rickets, autosomal dominant; Tumoral calcinosis, hyperphosphatemic, familial, 2 AD/AR Pediatric Dental; Renal; Musculoskeletal Renal In Hypophosphatemic rickets, autosomal dominant, treatment with both phosphate and high-dose vitamin D can be effective; In Tumoral calcinosis, hyperphosphatemic, phosphate reduction (eg, with dietary means and phosphate-binding agents) can be beneficial 5925614; 5173181; 4538804; 4353218; 3659264; 2777854; 1353055; 9024275; 11062477; 12541190; 15590700 FGF3 3681 2248 Deafness, congenital with inner ear agenesis, microtia, and microdontia AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Dental Audiologic/Otolaryngologic The condition may typically be recognizable from physical examination Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 17236138; 18435799; 18701883; 21480479 FGF5 3683 2250 Trichomegaly AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24989505 FGF8 3686 2253 Hypogonadotropic hypogonadism 6, with or without anosmia AD/Digenic Pediatric Allelic with Holoprosencephaly (AD) Craniofacial; Dental; Endocrine; Musculoskeletal; Neurologic Endocrine Relatively complex patterns of inheritance (eg, involving variants in FGFR1) have been described In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 18596921; 21045958; 21832120; 20301509; 21976454; 22319038 FGF9 3687 2254 Multiple synostoses syndrome 3 AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19589401 FGFR1 3688 2260 Hypogonadotropic hypogonadism 2 with or without anosmia; Trigonocephaly 1; Jackson-Weiss syndrome; Pfeiffer syndrome AD Pediatric Allelic with Hartsfield syndrome (AD/AR); Osteoglophonic dysplasia (AD) Audiologic/Otolaryngologic; Craniofacial; Dental; Endocrine; Genitourinary; Musculoskeletal; Neurologic Audiologic/Otolaryngologic; Endocrine Complex inheritance models, such as inolving digenic inheritance/synergistic effects (eg, with GNRHR, NELF, as well as other FGF8-network associated genes) has been reported In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required; Some individuals with FGFR1 variants may have hearing loss, and appropriate interventions may be beneficial as relates to language and speech development 14316612; 7422392; 6881209; 7874169; 8939381; 9475589; 11173846; 10861678; 11420131; 11297579; 2627230; 14564217; 16418210; 15625620; 16470795; 16606836; 17959774; 17360555; 20301509; 17235395; 22035731; 21700882; 23643382; 23812909; 25394172 FGFR2 3689 2263 Lacrimoauriculodentodigital syndrome; Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis; Craniofacial-skeletal-dermatological dysplasia; Crouzon syndrome; Jackson-Weiss syndrome; Pfeiffer syndrome; Apert syndrome; Beare-Stevenson cutis gyrata syndrome AD Pediatric Allelic with Bent bone dysplasia syndrome (AD); Scaphocephaly, maxillary retrusion, and mental retardation (AD) Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic Audiologic/Otolaryngologic FGFR2-related craniosynostosis can include deafness, and may be clinically recognizable, including by outer ear malformations Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 13801313; 5781468; 1271196; 660365; 1519658; 7874170; 7987400; 7674004; 7719333; 8528214; 7719345; 7795583; 7719344; 8644708; 8673103; 8696350; 8683284; 8651276; 9002682; 9150725; 9605588; 9714439; 9664610; 9585583; 9475590; 9475591; 10076886; 10076887; 10067911; 9973282; 10712195; 10951518; 10945669; 10633130; 10735635; 11343323; 12400058; 12900791; 15996217; 15793702; 16440883; 16061565; 16969861; 16876521; 16691624; 16501574; 17529973; 18247426; 19610084; 22387015 FGFR3 3690 2261 Camptodactyly, tall stature, and hearing loss (CATSHL) syndrome; Crouzon syndrome with acanthosis nigricans; Lacrimoauriculodentodigital syndrome; Muenke syndrome AD/AR Pediatric Allelic with Thanatophoric dysplasia, type I (AD), Thanatophoric dysplasia, type II (AD); Severe achondroplasia with developmental delay and acanthosis nigricans (AD); Hypochondroplasia (AD); Achondroplasia (AD) Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Musculoskeletal; Neurologic Audiologic/Otolaryngologic Certain variants in FGFR3 (such as result in CATSHL or Muenke syndrome) can result in congenital hearing loss, and thecondition may not be recognized early Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 5783850; 4697848; 474637; 3631079; 2650599; 7968151; 8078586; 7913883; 7847369; 7670477; 7493034; 7758520; 7773297; 8589699; 7647778 ; 8585566; 8841188; 8845844; 8923856; 8834055; 8880573; 9279764; 9042914; 9842995; 9600744; 9580776; 3631079; 9279753; 3228140; 9525367; 9733026; 9585583; 9450868; 9797588; 9677066; 10360402; 10360393; 10360392; 10053006; 11055896; 11186939; 10777366; 12116251; 15517832; 16912704; 15241680; 16353253; 16501574; 16411219; 17033969 18000976; 17935505; 17764078; 18000903; 17360555; 17879967; 17895900; 18266238; 18000903; 19449410; 20301540; 20624921; 9842995; 20301588; 19215249; 21204234; 20301331; 20301628; 21403557; 21403567; 22038757; 21971908; 22085076; 22446440; 22565872; 23044018; 23378035; 24168007; 24864036 FGG 3694 2266 Afibrinogenemia, congenital; Dysfibrinogenemia, congenital AD/AR Pediatric Hematologic Hematologic Individuals with afibrinogenemia/dysfibrinogenemia are at risk of a variety of bleeding diatheses; preventive or treatment-based (eg, with fibrinogen in the case of congenital afibrinogenemia) may be beneficial 4956920; 4427684; 6886002; 4002201; 3563970; 3708159; 3742050; 3337908; 2617471; 2496144; 2257302; 2328317; 7635941; 9746756; 2971042; 2971046; 2738036; 2819242; 2071611; 1471077; 1733971; 8470043; 7740487; 8822581; 9368024; 11001902; 11071644; 11001903; 11435303; 11986213; 17854317; 18832913; 19551918; 20135062; 20580695; 20589319; 20978265 FH 3700 2271 Hereditary leiomyomatosis and renal cell cancer AD Pediatric Allelic with Fumarase deficiency (AR) Biochemical; Dermatologic; Neurologic; Obstetric; Oncologic Obstetric; Oncologic Regular surveillance for dermatologic and uterine neoplasms can be beneficial in order to allow early detection and treatment (which can include medical management and/or surgical excision); Surveillance for renal neoplasms can allow early detection and treatment, which may include total nephrectomy 13520698; 6616883; 3736629; 3807970; 8200987; 11248088; 11865300; 16757530; 15937070; 20301430; 20618355; 21398687; 21404119; 22069215; 23320739; 23254734; 23612258; 23652956; 24346898; 32413184 FHL1 3702 2273 Reducing body myopathy, X-linked 1A, with infantile or early childhood onset; Reducing body myopathy, X-linked 1B, with late childhood or adult onset; Emery-Dreifuss muscular dystrophy 6, X-linked; Myopathy, X-linked, with postural muscle atrophy; Uruguay faciocardiomusculoskeletal syndrome XL Pediatric Allelic with Scapuloperoneal myopathy, X-linked dominant (XL) Cardiovascular; Musculoskeletal Cardiovascular In reducing body myopathy, dilated cardiomyopathy has been described, but well after clinical onset; In Myopathy with postural muscle atrophy and Emery-Dreifuss muscular dystrophy 6, heart failure can be deadly, perhaps related to hypertrophic cardiomyopathy; In Emery-Dreifuss muscular dystrophy 6, arrhythmias have been desribed, as well as sudden cardiac death; In all situations, survelliance and early medical management could be beneficial, but the condition may not be easily clinically recognizable Surveillance for cardiovascular disease (eg, cardiomyopathy, arrhythmias) and early medical treatment may reduce morbidity 4250729; 7722535; 8619529; 11102932; 16919903; 18179901; 18952429; 18274675; 18179888; 19716112; 19181672; 19687455; 19171836; 20186852; 26933038 FIBP 3705 9158 Thauvin-Robinet-Faivre syndrome AR Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal Oncologic The condition may include increased risk of Wilms tumor, and awareness may allow surveillance, early diagnosis, and management 26660953; 27183861 FIG4 16873 9896 Amyotrophic lateral sclerosis 11; Charcot-Marie Tooth disease, autosomal recessive, type 4J; Polymicrogyria, bilateral temporooccipital; Yunis-Varon syndrome AD/AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17572665; 18758830; 19118816; 21705420; 23623387; 24598713; 24878229 FIGLA 24669 344018 Premature ovarian failure 6 AD Pediatric Endocrine; Obstetric Obstetric Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency 18499083 FITM2 16135 128486 Siddiqi syndrome AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Musculoskeletal; Neurologic Audiologic/Otolaryngologic Among other findings, individuals may have prelingual hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 28067622; 30214770; 30288795 FKBP10 18169 60681 Osteogenesis imperfecta, type XI; Bruck syndrome 1 AR N/A N/A Dental; Musculoskeletal General Bisphosphonates may reduce fracture frequency, but it is unclear if early (genomic) diagnosis would be additionally beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20362275; 20696291; 20839288; 21567934 FKBP14 18625 55033 Ehlers-Danlos syndrome, kyphoscoliotic type, 2 AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Genitourinary; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular Cardiovascular complications, including aortic rupture, have been described, and awareness and surveillance may allow rapid diagnosis and treatment, which may ameliorate morbidity and mortality 22265013; 24773188 FKRP 17997 79147 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5; Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5 AR Pediatric Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular Individuals have been described with cardiovascular complications (eg, left-ventricular dysfunction), and recognition may allow surveillance (eg, with echocardiogram) and early medical management aimed at optimizing cardiac function; Cardiac transplantation has been described 9577386; 10838249; 11592034; 11320179; 11741828; 12707425; 14647208; 15121789; 14523375; 15580560; 16634037; 16476814; 17336067; 18060779; 18639457; 18671187; 19705481; 19917824; 20301582; 20627570 FKTN 3622 2218 Cardiomyopathy, dilated, 1X; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4; Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 AR Pediatric Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular; Musculoskeletal Surveillance for cardiovascular complications may allow early diagnosis and treatment, which may ameliorate morbidity and mortality; Cardiomyopathy, dilated, 1X has been reported as being treated with transplant; Individuals with Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 has been reported as benefiting from treatment with steroids 7258547; 8124873; 9690476; 10545611; 10817652; 12601708; 17036286; 17044012; 17878207; 18177472; 19015585; 19342235; 19299310; 19179078; 19842201; 20627570; 20961758 FLAD1 24671 80308 Lipid storage myopathy due to FLAD1 deficiency AR Pediatric Biochemical; Cardiovascular; Neurologic Biochemical; Cardiovascular Individuals have shown clinical improvement with dietary management (riboflavin); The condition has been described with cardiomyopathy, and awareness may allow prompt diagnosis and management (eg, with medical management and ICD) 25058219; 27259049 FLCN 27310 201163 Birt-Hogg-Dube syndrome; Pneumothorax, primary spontaneous AD Adult Dermatologic; Oncologic; Pulmonary Oncologic; Pulmonary Individuals are at risk for a number of types of neoplasms, and surveillance and early diagnosis/treatment may be beneficial; Some individuals may demonstrate isolated pneumothorax, but may be at elevated risk for malignancies; Affected individuals commonly have recurrent pneumothoraces, and early pleurodesis may beneficial) 596896; 10522666; 11533913; 12471204; 12204536; 15657874; 15852235; 17496196; 18505456; 18234728; 19320655; 20413710; 20618353; 22146830; 23264078; 23414156; 23542717; 23715758; 23846428; 23995526 FLG 3748 2312 Icthyosis vulgaris AD/AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12473059; 12838398; 17030239; 16550169; 16444271; 16815158; 17291859; 21692775; 21712002; 21790526; 22299762; 22951058; 22962861; 22989708 FLG2 33276 388698 Peeling skin syndrome 6 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28884927; 29505760; 29758285 FLI1 3749 2313 Thrombocytopenia, Paris-Trousseau type; Bleeding disorder, platelet type 21 AD/AR Pediatric Hematologic Hematologic Individuals may have bleeding tendency, and precautions (eg, in surgical situations) may be beneficial 14597985; 22887642; 24100448; 26316623; 28255014 FLNA 3754 2316 Cardiac valvular dysplasia, X-linked; Heterotopia, periventricular, 1; Intestinal pseudoobstruction, neuronal, X-linked/Congenital short bowel syndrome XL Pediatric Allelic with Dysmorphic facies with multi-organ anomalies (XL); FG syndrome 2 (XL); Frontometaphyseal dysplasia 1 (XL); Melnick-Needles syndrome (XL); Otopalatodigital syndrome, type I (XL); Otopalatodigital syndrome, type II (XL); Periventricular nodular heterotopia 1 (XL); Terminal osseus dysplasia (XL) Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Pulmonary; Renal Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal In Cardiac valvular dysplasia, X-linked, surveillance for and correction of valvular anomalies can be beneficial; Individuals with Heterotopia, periventricular may have cardiac and vascular anomalies, which may warrant surveillance and medical/surgical management; For hearing loss, early recognition may allow beneficial interventions that can help with speech and language development; In Intestinal pseudoobstruction, neuronal, X-linked/Congenital short bowel syndrome, individuals have been described as benefiting from early introduction of enteral feeds, with later weaning from parenteral nutrition, and awareness of the risk of other GI-related complications may allow prompt recognition and management 5938049; 5807657; 8230166; 8290091; 8644737; 9883725; 9800904; 9497244; 10982965; 11857561; 11914408; 12612583; 15249610; 14988809; 15864382; 15940695; 15654694; 15523633; 15917206; 15654694; 15668422; 16299064; 16538226; 16596676; 16926860; 17152064; 17190868; 17264970; 17357080; 17431908; 17632775; 18209785; 18427995; 18854860; 19917821; 20301567; 20014127; 20598277; 20730588; 20888935; 21031081; 21194575; 21412975; 21484998; 21815255; 21960593; 22238415; 22366253; 22740120; 23037936; 23873601 FLNB 3755 2317 Larsen syndrome; Spondylocarpotarsal synostosis syndrome AD/AR Pediatric Allelic with Boomerang dysplasia (AD); Atelosteogenesis, type I (AD); Atelosteogenesis, type III (AD) Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal Audiologic/Otolaryngologic; Musculoskeletal Surveillance and early intervention related to cervical spine stability can allow early detection and treatment of manifestations; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 8609132; 12955767; 14991055; 15994868; 17202879; 16801345; 18257094; 18377309; 18386804; 20301736; 22190451; 22354125 FLNC 3756 2318 Cardiomyopathy, familial hypertrophic 26 (Cardiomyopthy, familial restrictive 5); Myopathy, distal, 4; Myopathy, myofibrillar, 5 AD Adult Cardiovascular; Musculoskeletal Cardiovascular Individuals (including with Distal myopathy or Myofibrillar myopathy) have been described with cardiomyopathy, and surveillance (eg, including echocardiography an electrocardiography) may allow early diagnosis and management 15929027; 15824355; 19050726; 21620354; 22131542; 22806379; 23109048; 25351925; 26666891 FLRT3 3762 23767 Hypogonadotropic hypogonadism 21, with or without anosmia AD/Digenic/Multigenic Pediatric Audiologic/Otolaryngologic; Endocrine; Musculoskeletal; Neurologic Endocrine Relatively complex genetic models of disease have been described (eg, involving variants in other FGF8-network-associated genes) In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 6881209; 23643382 FLT4 3767 2324 Lymphatic malformation 1 AD/AR Pediatric Allelic with Congenital heart defects, multiple types, 7 (AD) Allergy/Immunology/Infectious; Cardiovascular Allergy/Immunology/Infectious Biallelic inheritance has been described Treatment includes early and aggressive treatment of infections, as well as prophylactic antibiotics in some instances 14295660; 9817924; 10835628; 12960217; 15689446; 16965327; 16924388; 19002718; 19289394; 20301417; 22768468; 28991257; 30232381 FLVCR1 24682 28982 Ataxia, posterior column, with retinitis pigmentosa AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9409377; 9855554; 21070897; 21267618; 22279524; 22483575 FLVCR2 20105 55640 Proliferative vasculopathy and hydraencephaly-hydrocephaly syndrome AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Treatment may involve dietary modification (eg, to restrict trimethylamine precursors), and medical/dietary treatment (eg, with agents such as metronidazole, neomycin, lactulose, copper chlorphyllin, activated charcoal, (E, E)-2, 4-undecadienal) as well as riboflavin supplementation (the use of specific pH soaps may be beneficial as well) 7474897; 9398858; 9846928; 10646019; 10485731; 12653714; 12893987; 12938085; 15565078; 16601883; 20301282; 22126753; 23430514 FMN2 14074 56776 Mental retardation, autosomal recessive, 47 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25480035 FMO3 3771 2328 Trimethylaminuria AR Pediatric Biochemical Biochemical Treatment may involve dietary modification (eg, to restrict trimethylamine precursors), and medical/dietary treatment (eg, with agents such as metronidazole, neomycin, lactulose, copper chlorphyllin, or activated charcoal) as well as riboflavin supplementation (the use of specific pH soaps may be beneficial as well) 7474897; 9398858; 9846928; 10646019; 10485731; 12653714; 12893987; 12938085; 15565078; 16601883; 22126753 FMR1 3775 2332 Premature ovarian failure 1 XL Pediatric Allelic with Fragile X syndrome (XL); Fragile X tremor/ataxia syndrome (XL) Craniofacial; Endocrine; Neurologic; Obstetric Obstetric Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency 5794013; 7333582; 6958915; 6711591; 3398009; 2195034; 1944467; 9719368; 10208170; 10325264; 11445641; 12730995; 12638084; 12533098; 14747503; 15065016; 15052536; 16043804; 16493202; 17166801; 18348275; 19724010; 19411303; 20228389; 19542082; 21518720; 21188402; 21300345; 21912443; 23703681 FN1 3778 2335 Glomerulopathy with fibronectin deposits 2; Spondylometaphyseal dysplasia, corner fracture type AD N/A N/A Biochemical; Musculoskeletal; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2869211; 1544672; 7747733; 7564073; 12042895; 18268355; 29100092 FOLR1 3791 2348 Neurodegeneration due to cerebral folate deficiency AR Pediatric Biochemical; Neurologic Biochemical Diagnosis is critical, as the natural history includes severe neurodegeneration and neurologic impairment, and treatment with folinic acid (it is important to note that response to such treatment is better when initiated in early childhood) can reverse symptoms and improve brain abnormalities and function 19732866; 20857335; 21752681; 22586289; 22734130 FOXC1 3800 2296 Axenfeld-Rieger syndrome, type 3; Anterior segment dysgenesis 3, multiple types AD Adult Audiologic/Otolaryngologic; Cardiovascular; Musculoskeletal; Ophthalmologic Cardiovascular; Ophthalmologic; Pharmacogenomic Individuals with Axenfeld-Rieger anomaly have a high risk of developing glaucoma, but treatment may not be effective in the majority of cases; Awareness of cardiac anomalies (eg, valvular anomalies leading to congestive heart failure have been described) may allow early detection and treatment; Agents that may contribute to glaucoma should be avoided 9445211; 9792859; 9620769; 11004268; 11007653; 10713890; 12036988; 11170889; 12036988; 12614756; 12614756; 17197537; 18498376; 19668217; 19793056; 23239455 FOXC2 3801 2303 Lymphedema-distichiasis syndrome AD N/A N/A Cardiovascular; Dermatologic; Musculoskeletal; Ophthalmologic General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14269895; 3573000; 10086462; 11078474; 11499682; 11694548; 12485195; 12114478; 15523639; 17372167; 19760751; 20186799; 20301630; 20450314; 20552815; 21918810; 22349027; 22768468 FOXE1 3806 2304 Thyroid cancer, nonmedullary 4; Hypothyroidism, thyroidal, with spiky hair and cleft palate (Bamforth-Lazarus syndrome) AD/AR Pediatric (Hypothyroidism, thyroidal, with spiky hair and cleft palate)/Adult (Thyroid cancer, nonmedullary 4) Craniofacial; Dermatologic; Endocrine; Musculoskeletal; Oncologic Endocrine; Oncologic For Thyroid cancer, nonmedullary 4, individuals have been described as being susceptible to nonmedullary thyroid cancer, and awareness may allow early surveillance, diagnosis, and management; For Hypothyroidism, thyroidal, with spiky hair and cleft palate (Bamforth-Lazarus syndrome), the condition may be clinically recognizable, but recognition and prompt treatment of hypothyroidism can be beneficial 2918525; 8320710; 9697705; 12165566; 16882747; 17717707; 17318017; 19779022; 20484477; 20453517; 20094846; 21981779; 21311165; 25381600 FOXE3 3808 2301 Aortic aneurysm, familial thoracic 11, susceptibility to; Anterior segment dysgenesis 2 AD/AR Pediatric Allelic with Cataract 34 (AD) Cardiovascular; Ophthalmologic Cardiovascular; Ophthalmologic Individuals with Anterior segment dysgenesis have been described with glaucoma, and surveillance and early treatment may be beneficial, and agents that may contribute to glaucoma should be avoided; Individuals with Aortic aneurysm, familial thoracic 11 have been described as presenting with acute ascending aortic dissection and dilatation, and awareness may allow surveillance and early medical and surgical management 3550563; 11159941; 16826526; 21150893; 26854927; 27218149 FOXF1 3809 2294 Alveolar capillary dysplasia with misalignment of pulmonary veins AD N/A N/A Cardiovascular; Genitourinary; Gastrointestinal; Musculoskeletal; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15520767; 19500772; 20425831; 22990143; 23407133; 23444129; 23505205; 24842713 FOXG1 3811 2290 Rett syndrome, congenital variant AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18571142; 19578037; 19564653; 20736978; 21441262; 21536641; 21910242; 21953941; 22091895; 22129046; 22258524; 22415763; 22670136 FOXH1 3814 8928 Holoprosencephaly; Congenital heart malformations AD N/A N/A Cardiovascular; Craniofacial; Endocrine; Neurologic General Individuals with holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18538293 FOXI1 3815 2299 Deafness, autosomal recessive 4, with enlarged vestibular aqueduct AR Pediatric Audiologic/Otolaryngologic; Endocrine Audiologic/Otolaryngologic; Endocrine Digenic inheritance (with SLC26A4) has been reported Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Pendred syndrome, awareness of the potential for thyroid abnormalities may be beneficial to allow early detection and appropriate management 17503324 FOXJ1 3816 2302 Ciliary dyskinesia, primary, 43 AD Pediatric Allergy/Immunology/Infectious; Cardiovascular; Genitourinary; Neurologic; Pulmonary Allergy/Immunology/Infectious; Pulmonary Pulmonary surveillance may be beneficial to assess respiratory function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial; Individuals have been described requiring shunting due to obstructive hydrocephalus, and awareness may allow early interventions 31630787 FOXL2 1092 668 Blepharophimosis, epicanthus inversus, and ptosis; Premature ovarian failure 3 AD Pediatric Craniofacial; Endocrine; Genitourinary; Obstetric; Ophthalmologic Obstetric Awareness may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency (which is also reported in women with BPES) 11175783; 12149404; 15962237; 16283882; 17089161; 19429596; 21325395 FOXN1 12765 8456 T-cell lymphopenia with or without nail dystrophy, autosomal dominant; T-cell immunodeficiency, congenital alopecia, and nail dystrophy; T-cell immunodeficiency with thymic aplasia AD/AR Pediatric Allergy/Immunology/Infectious; Dermatologic Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported in cell immunodeficiency, congenital alopecia, and nail dystrophy, but has not been described as curative in T-cell lymphopenia with or without nail dystrophy, autosomal dominant; In T-cell immunodeficiency with thymic aplasia, thymus transplantation has been reported as curative 8911612; 10206641; 15180707; 18339010; 20429426; 20864124; 21507891; 31447097; 31566583 FOXP1 3823 27086 Mental retardation with language impairment and autistic features AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20571508; 20950788; 21572417; 22521361 FOXP2 13875 93986 Speech-language disorder 1 AD N/A N/A Musculoskeletal; Neurologic General Paternal deletions are associated with Russell-Silver syndrome, and may be related to speech-language involvement in the condition Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3265313; 11586359; 15326624; 15877281; 17033973; 16470794; 20301499; 22106036; 22105961; 22144704 FOXP3 6106 50943 Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked (IPEX) XL Pediatric Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Renal Allergy/Immunology/Infectious The condition may involve infectious and autoimmune manifestations For neutropenia, G-CSF can be effective; Bone marrow transplantation has been reported as effective if performed early; Prophylactic antibiotics can be beneficial; Immunosuppressive agents may be helpful 7040622; 2246696; 8482279; 8777684; 11120765; 11396442; 11137993; 11295725; 11137992; 20301297; 20842625; 21979562; 21741320; 21865090; 22132891; 23534934 FOXRED1 26927 55572 Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, uniquinol) may be beneficial, and surveillance for cardiac involvement may be beneficial in order to allow early management Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 20818383; 20858599 FRAS1 19185 80144 Fraser syndrome 1 AR N/A N/A Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12766769; 16894541; 17163535; 18671281; 22029163 FREM1 23399 158326 Bifid nose with or without anorectal and renal anomalies; Trigonocephaly 2; Manitoba oculotrichoanal syndrome AD/AR N/A N/A Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1554017; 11332973; 11822703; 17352387; 19732862; 21507892; 21931569; 23112756; 23221805 FREM2 25396 341640 Fraser syndrome 2; Cryptophthalmos, unilateral or bilateral, isolated AR N/A N/A Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15838507; 18203166; 18000968; 18671281; 30802441 FRMD4A 25491 55691 Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia (Fine-Flusser syndrome) AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25388005 FRMD7 8079 90167 Nystagmus, infantile periodic alternating, X-linked XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16020310; 16240070; 17013395; 18087240; 17768376; 19072571; 17962394; 21746984; 21303855; 21386928; 21746984; 22065930; 22262942; 22490987 FRMPD4 29007 9758 Mental retardation, X-linked 104 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25644381 FRRS1L 1362 23732 Developmental and epileptic encephalopathy 37 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27236917; 27239025 FSCN2 3960 25794 Retinitis pigmentosa 30 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11527955 FSHB 3964 2488 Hypogonadotropic hypogonadism 24 without anosmia AR Pediatric Endocrine; Obstetric Endocrine; Obstetric In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 4344039; 758600; 8220432; 9280841; 17961559 FSHMD1A 3966 2489 Facioscapulohumeral muscular dystrophy 1A AD/AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Musculoskeletal; Ophthalmologic Cardiovascular; Ophthalmologic Awareness and surveillance of cardiac manifestations, including arrhythmias (eg, with EKG), may allow early treatment, which may ameliorate morbidity and mortality; Individuals may present with ophthalmologic anomalies (including retinal telangiectasia, which may rarely progress to Coats disease), and recognition may allow surveillance and prompt management 15411118; 6704043; 6745940; 3580827; 1927871; 1363881; 7987304; 9506542; 10631134; 14557558; 15154112; 16178028; 17229919; 17563001; 20301616; 21984394; 22217918; 22482803 FSHR 3969 2492 Ovarian hyperstimulation syndrome; Ovarian dysgenesis 1 AD/AR Pediatric Endocrine; Genitourinary; Obstetric Obstetric In Ovarian hyperstimulation syndrome, diagnosis may be beneficial for preconception/reproductive planning (eg, in order to avoid precipitating factors related to ovarian hyperstimulation); In Ovarian dysgenesis 1, genetic knowledge may be beneficial to allow Interventions such as preserving eggs in women with premature ovarian insufficiency 7553856; 9769327; 12498425; 11889179; 12930928; 12930927; 12930924; 17721928; 20087398 FSIP2 21675 401024 Spermatogenic failure 34 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30137358 FTCD 3974 10841 Glutamate formiminotransferase deficiency AR N/A N/A Biochemical General Early descriptions included benefits of folic acid treatment, but later descriptions call this into question, and the clinical consequences of the deficiency are unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5897668; 5956503; 4413489; 235753; 1272625; 12815595; 22108709; 29178637 FTH1 3976 2495 Hemochromatosis, type 5 AD Pediatric Hematologic Hematologic Preventive measures to ameliorate iron overload may be beneficial 11389486 FTL 3999 2512 L-ferritin deficiency; Neurodegeneration with brain iron accumulation 3; Hyperferritinemia with or without cataract AD/AR N/A N/A Hematologic; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7493028; 8558554; 7669675; 11438811; 11703332; 12200611; 12199804; 12746423; 15173247; 15280904; 15099026; 17142829; 18413574; 18854324; 20301320; 22020773; 22278127 ; 22515742; 23940258 FTO 24678 79068 Growth retardation, developmental delay, and facial dysmorphism AR N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19559399; 26378117 FTSJ1 13254 24140 Mental retardation, X-linked 9 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8288232; 10398246; 12239714; 15162322; 15342698; 18081026 FUCA1 4006 2517 Fucosidosis AR N/A N/A Biochemical; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4172303; 4241464; 4247654; 5026163; 1214294; 4128078; 7460371; 6538300; 2903667; 3409541; 2642067; 2012122; 8719750; 9039984; 9762612; 10094192; 12408193; 17427030; 18504684 FUS 4010 2521 Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia; Tremor, hereditary essential, 4 AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12840784; 12858291; 19741216; 19251627; 19741215; 19251628; 19861302; 20385912; 20577002; 20660363; 20668259; 22863194; 22980027; 22999566; 23046859 FUT1 4012 2523 Bombay phenotype BG Pediatric Hematologic Hematologic Digenic inheritance (with FUT2) has been described Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 14918471; 13269394; 13767673; 5763629; 7246545; 7180848; 6177241; 6859043; 2118655; 7912436; 9299444 FUT2 4013 2524 Bombay phenotype BG Pediatric Hematologic Hematologic Digenic inheritance (with FUT1) has been described Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 14918471; 13269394; 13767673; 5763629; 7246545; 7180848; 6177241; 6859043; 2118655; 7912436; 9299444 FUT3 4014 2525 Blood group, Lewis system AD Pediatric Hematologic Hematologic Variants may be associated with a blood group may be important in specific situations (eg, related to transfusion) 2922027; 7961897; 8943285; 9703429; 11668626; 15383031 FUT6 4017 2528 Fucosyltransferase 6 deficiency AR N/A N/A Biochemical General The clinical relevance of the condition is unclear 8175676 FUT8 4019 2530 Congenital disorder of glycosylation with defective fucosylation 1 AR N/A N/A Biochemical; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29304374 FUZ 26219 80199 Neural tube defects, susceptibility to AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21840926 FXN 3951 2395 Friedreich ataxia 1 AR Pediatric Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular Though frequently clinically recognizable, the majority of individuals have cardiomyopathy, and medications (eg, antiarrhythmics, medications for cardiac-failure, anticoagulants, and pacemaker insertion) may be beneficial; Heart transplantation has been described 13872187; 5673214; 5533984; 4206197; 7272714; 6231891; 8057123; 7695235; 8596916; 8623752; 8815938; 8751856; 9150176; 9142000; 9245990; 9259271; 9539351; 10399865; 10543403; 10533031; 10500204; 11425956; 11843702; 11857753; 15539131; 19347027; 20301458; 21700145; 21570254; 22409940; 22522441; 22691228; 22752483; 22752493; 22764179; 23196337; 23242090 FXR1 4023 8087 Myopathy, congenital, with respiratory insufficiency and bone fractures; Myopathy, congenital proximal, with minicore lesions AR N/A N/A Musculoskeletal; Neurologic; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30770808 FXYD2 4026 486 Hypomagnesemia 2, renal AD Pediatric Renal Renal Surveillance for and treatment of electrolyte abnormalities can be beneficial (eg, to avoid sequelae such as pseudogout, as has been described in affected individuals) 3298795; 11062458 FYB1 4036 2533 Thrombocytopenia 3 AR Pediatric Hematologic Hematologic Individuals have been described with bleeding tendency, and awareness may allow early diagnosis, preventive measures, and early and aggressive treatment of bleeding episodes 23650215; 25516138; 25876182 FYCO1 14673 79443 Cataract, autosomal recessive congenital 2 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11519376; 21636066 FZD2 4040 2535 Omodysplasia 2 AD N/A N/A Craniofacial; Genitourinary; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25759469 FZD4 4042 8322 Exudative vitreoretinopathy 1 AD/Digenic N/A N/A Ophthalmologic General Digenic inheritance (with LRP5 has been reported) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12172548; 14507768; 15488808; 15981244; 21097938 FZD6 4044 8323 Nail disorder, nonsyndromic noncongenital 10 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21665003 G6PC1 4056 2538 Glycogen storage disease Ia AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Oncologic; Renal Biochemical; Gastrointestinal; Oncologic; Renal Dietary measures (eg, with Glycosade or cornstarch) can be beneficial to allow optimal glucose levels and promote growth and development (additionally, specific carbohydrate sources should be limited); Allopurinol to prevent gout and lipid-lowering medications to prevent hyperlipidemia may be necessary when dietary therapy is ineffective; Citrate supplementation and ACE inhibitors may help prevent development of decrease renal complications, though renal transplant may ultimately be necessary; Surveillance for and treatment of hepatic neoplasms (including liver transplant in some) can be beneficial 5240134; 4302545; 204806; 204758; 6928317; 6581385; 2883397; 3030527; 3422104; 2199830; 2109144; 1743219; 8391447; 8211187; 8448918; 8319728; 8441093; 8319729; 8319726 ; 8203427; 8273986; 7668282; 7573034; 8733042; 8758135; 9427147; 9332655; 10472532; 10070617; 10748407; 11241046; 11757580; 15151508; 19762333; 20301489; 20720360; 21058447; 21481415; 21620082; 29223626 G6PC3 24861 92579 Neutropenia, severe congenital, 4, autosomal recessive AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Hematologic; Neurologic; Renal Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Genitourinary; Hematologic Antiinfectious prophylaxis (including with G-CSF) and early and aggressive treatment of infections may be beneficial; Awareness of other manifestations, including affecting the cardiac, endocrine, and urogenital systems may allow early diagnosis and treatment 19696212; 19118303; 20799326; 20616219; 20717171; 21285905; 22050868 G6PD 4057 2539 Glucose-6-phosphate dehydrogenase deficiency XL Pediatric Allergy/Immunology/Infectious; Hematologic Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic The condition involves predisposition to anemia, which can be precipitated by, among other things, certain medications; Complete G6PD deficiency can result in chronic granulamotous disease secondary to neutrophil deficiency Hemolytic reactions can result from a variety of triggers, such as infections, dietary items, and medications, and avoidance of precipitating agents (or redosing in order to decreased the chance of certain medication reactions, as well as prompt removal in the case of a reaction) can be beneficial; Individuals are also susceptible to neonatal jaundice; Complete G6PD deficiency can result in immunodeficiency, and prophylactic measures, as well as prompt and aggressive treatment of infections, can be beneficial 13360274; 13500095; 14014720; 14158057; 4388132; 5369703; 5305539; 4401271; 4125296; 5448; 3681550; 3446582; 2836867; 2912069; 2910917; 2602358; 2248331; 2263506; 2157298; 2321910; 1999409; 2005960; 1303182; 1611091; 1551674; 1536798; 1562739; 8471773; 8490627; 8364584; 7949118; 8533762; 7617034; 8627445; 8807322; 8826878; 8579052; 8956035; 9427729; 9674740; 10666231; 11048840; 11433050; 11803413; 11857737; 12028056; 15349799; 16204390; 15724035; 16155737; 16493607; 16607506; 16528451; 17444323; 18177777; 19112496; 18379570; 19177059; 20007901; 20701405; 21641489; 22573495; 22795224; 23237606; 23384623; 23573906; 23714236; 23815264; 23834949; 23860572; 23874116; 23874768 GAA 4065 2548 Glycogen storage disease II AR Pediatric Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Pulmonary Biochemical; Cardiovascular; Pharmacogenomic Enzyme therapy is available; Disease-specific care of cardiomyopathy may be beneficial (eg, some standard drugs are contraindicated, and there is high risk for arrhythmias and sudden cardiac death) 5217754; 4288232; 5229488; 5247277; 5240358; 6810200; 6401355; 3084996; 3093639; 3090917; 3322184; 3135192; 3282727; 3288378; 2403755; 2243227; 2203258; 1895140; 11071489; 10931430; 11286229; 12601120; 12897283; 15668445; 15985590; 16433701; 17190962; 16917947; 19047571; 19047572; 20301438; 21543987; 21518733; 21637107; 22253258; 22334186; 22353292; 22365055; 22492103; 22538254; 22539577; 22581536; 22616199; 23884227; 24008937; 24011652; 24044919 GAB1 4066 2549 Deafness, autosomal recessive 26 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Individuals with heterozygous variants in METTL13 may not develop deafness Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 29408807 GABBR2 4507 9568 Epileptic encephalopathy, early infantile, 59; Neurodevelopmental disorder with poor language and loss of hand skills AD N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25262651; 26740508; 28856709; 29100083; 29369404 GABRA1 4075 2554 Epilepsy, idiopathic, generalized, susceptibility to, 13; Epilepsy, childhood absence, susceptibility to, 4; Developmental and epileptic encephalopathy 19 AD N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11992121; 16718694; 20551311; 24623842 GABRA2 4076 2555 Developmental and epileptic encephalopathy 78 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29422393; 29961870; 31032849 GABRA5 4079 2558 Developmental and epileptic encephalopathy 79 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29961870; 31056671 GABRB1 4081 2560 Developmental and epileptic encephalopathy 45 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23934111; 26950270; 27273810 GABRB2 4082 2561 Developmental and epileptic encephalopathy 92 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25124326; 27789573; 29100083 GABRB3 4083 2562 Epilepsy, childhood absence, susceptibility to, 5; Developmental and epileptic encephalopathy 43 AD N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12189488; 11920158; 11810291; 16835263; 17957331; 18514161; 22303015; 23934111; 27476654 GABRG2 4087 2566 Generalized epilepsy with febrile seizures plus, type 3; Familial febrile seizures 8; Developmental and epileptic encephalopathy 74 AD N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Many variants may involve a susceptibility locus and/or evidence or clinical applicability is unclear 11326274; 11326275; 1748509; 12117362; 17190949; 19261880; 20308251; 23069679; 27864268 GAD1 4092 2571 Cerebral palsy, spastic quadriplegic, 1; Developmental and epileptic encephalopathy 89 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9084927; 15571623; 32282878 GAL 4114 51083 Epilepsy, familial temporal lobe, 8 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25691535 GALC 4115 2581 Krabbe disease AR Pediatric Biochemical; Neurologic Biochemical BMT/HSCT have been described, and in presymptomatic infants as well as older mildly-affected individuals, this treatment may improve and preserve cognitive function (ie, presymptomatic transplant has much better neurological outcomes) 14024503; 3123790; 4773865; 1817026; 1817027; 2056315; 1891085; 8297359; 7581365; 9449482; 8940268; 9338580; 9545360; 10833326; 15901860; 16607461; 17579360; 19332366; 21070211; 20301416; 20886637; 22115770; 22704718; 23462331; 23276707 GALE 4116 2582 Galactosemia III AR Pediatric Biochemical; Gastrointestinal; Neurologic; Ophthalmologic; Renal Biochemical; Neurologic The generalized form, which typically manifests clinically in infancy upon exposure to lactose-containing diet, can result in lethal sequelae, and can be treated or prevented through dietary means (galactose/lactose restriction); Though data are unclear, individuals with intermediate forms of disease may also benefit from galactose restriction as well 4644860; 4785150; 404274; 7305435; 7227386; 6408303; 3948246; 9700591; 3141714; 8295413; 9326324; 9700591; 9538513; 9973283; 10086948; 11117433; 14970742; 15639193; 16301867; 16302980; 16385452; 18188677; 19250319; 19904445; 20725869; 21290786; 23430501 GALK1 4118 2584 Galactosemia II AR Pediatric Biochemical; Neurologic; Ophthalmologic Biochemical Individuals may manifest with early-onset cataracts, and dietary measures (galactose/lactose restricted diet) can be effective; The presence of pseudotumor cerebri has been described, and awareness may allow prompt recognition and management 3043741; 5109408; 5034870; 74495; 490246; 7670469; 8908517; 10570908; 10521295; 10790206; 11139256; 11978884; 12705493; 15024738; 17517531; 20405025; 21290184; 22154682; 22632133 GALM 24063 130589 Galactosemia IV AR Pediatric Biochemical; Ophthalmologic Biochemical Dietary management (with a galactose-free diet) has been reported as resulting in normal galactose levels; some have been reported as resuming a normal diet in childhood and maintaining normal galactose levels 30451973; 30910422 GALNS 4122 2588 Mucopolysaccharidosis IVA (Morquio syndrome A) AR Pediatric Biochemical; Dental; Musculoskeletal; Ophthalmologic; Pulmonary Biochemical; Cardiovascular; Musculoskeletal; Ophthalmologic; Pulmonary Enzyme replacement therapy has been shown to be beneficial related to certain clinical (as well as biochemical) parameters; The condition may involve cardiac manifestations including cardiac valve abnormalities, and awareness may allow surveillance and prompt recognition and treatment (eg, through surgical interventions); As individuals are at risk of injury due to spinal stenosis, awareness may allow appropriate precautions (eg, during surgeries or medical procedures); Awareness of the risk of certain ophthalmological complications (including glaucoma) can allow prompt awareness and treatment; Measures to optimize pulmonary function can be beneficial 770035; 5704829; 17569489; 3129221; 7607677; 8651279; 9298823; 10814710; 16287098; 20574428; 22078177; 22178352; 22231379; 22358740; 22521955; 22976768; 23313879; 23371450; 23385297; 23452954; 23665161; 23844448; 23860310; 23876334; 24810369; 25496828; 25545067; 25582974; 28595941 GALNT12 19877 79695 Colorectal cancer, susceptibility to, 1 AD Adult Oncologic Oncologic Surveillance for colorectal neoplasms may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality 19617566; 22461326 GALNT2 4124 2590 Congenital disorder of glycosylation, type IIt AR N/A N/A Craniofacial; Endocrine; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27508872; 32293671 GALNT3 4125 2591 Tumoral calcinosis, hyperphosphatemic, familial, 1 AR Pediatric Dermatologic; Musculoskeletal; Renal Renal Individuals may manifest with sequelae (ie, increased calcium phosphate deposition) of hyperphosphatemia due to increased renal phosphate absorption, and phosphate reduction (eg, with dietary means and phosphate-binding agents) can be beneficial, though families for whom treatment was not effective have been reported 3774168; 4538804; 3998061; 3839626; 3659264; 338191; 2777854; 12541190; 15133511; 15599692; 15687324; 16528452; 16528452; 16567474; 16940445; 17129170; 17311862; 17351710; 17853462; 18322299; 18618993; 18982401; 19255228; 20358599; 21347749; 22142751 GALT 4135 2592 Galactosemia I AR Pediatric Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Obstetric; Ophthalmologic; Renal Biochemical Although there is some controversy related to treatment of individuals with various enzymatic activities, dietary measures (eg,lactose-free and galactose-restricted diet, with vitamin supplementation aimed to prevent decreased bone mineralization) can be effective 1610789; 1766867; 7927329; 8040766; 8051928; 8112740; 8499924; 8522334; 8956044; 1897530; 1373122; 2011574; 5337683; 4926707; 4136146; 90818; 6290834; 2512439; 1706789; 8444204; 8198125; 7887416; 8692963; 8943248; 8969739; 9012409; 11261429; 10472536; 10424825; 10604151; 12595586; 16838075; 19224951; 19793842; 20075179; 20222886; 20301691; 20978943; 21059483; 21321007; 21735606; 21779791; 22461411; 22483615; 22944367; 23022339 GAMT 4136 2593 Cerebral creatine deficiency syndrome 2 (Guanidinoacetate methyltransferase deficiency) AR Pediatric Biochemical; Neurologic Biochemical Medical (eg, with creatine-monohydrate, L-ornithine, and/or sodium benzoate) as well as dietary (eg, with ornithine supplementation and protein/arginine restriction) has been reported to increase cerebral creatine, resulting in improvement or stabilization of clinical manifestations in all symptomatic individuals 7808840; 8651275; 9386672; 11196109; 15651030; 17171576; 17336114; 19027335; 20301745; 23031365; 24268530 GAN 4137 8139 Giant axonal neuropathy 1, autosomal recessive AR N/A N/A Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11062483; 11053687; 18595793; 19231187; 20301315; 20949505; 21356581 GANAB 4138 23193 Polycystic kidney disease 3 with or without polycystic liver disease AD Pediatric Cardiovascular; Gastrointestinal; Renal Cardiovascular; Gastrointestinal; Renal A number of manifestations can benefit from surveillance and early treatment, including surveillance for cardiovascular findings such as intracranial aneurysms and aortic dilation can allow early detection and treatment; Treatment for hypertension is frequently required (eg, with ACE inhibitors/angiotensin II receptor blockers); A number of agents should be avoided, including nephrotoxic agents, estrogens, smoking and agents that increase renal cysts; Additional considerations related to hepatic and other cyst-related manifestations may be beneficial 27259053 GARS1 4162 2617 Charcot-Marie-Tooth disease, type 2D; Neuropathy, distal hereditary motor, type VA AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8541851; 8872480; 10732809; 9879677; 12690580; 16769947; 19329989; 20169446; 20301420; 20301462; 22462675; 23279345 GAS1 4165 2619 Holoprosencephaly 4 AD N/A N/A Craniofacial; Endocrine; Neurologic General Individuals with holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20583177; 21842183 GAS8 4166 2622 Ciliary dyskinesia, primary, 33 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 26387594 GATA1 4170 2623 Thrombocytopenia with beta-thalessemia, X-linked; Anemia, X-linked, with or without thrombocytopenia and platelet abnormalities; Dyserythropoietic anemia with thrombocytopenia XL Pediatric Hematologic Hematologic; Pharmacogenomic Individuals, especially males (though females have been reported with bleeding complications, such as in the postpartum period), may require preventive measures and treatment (eg, with platelet and/or RBC transfusions) related to bleeding diathesis; Certain activities and agents (eg, contact sports and medications such as NSAIDS) should be avoided in some individuals; BMT has been reported 871527; 10700180; 11418466; 11675338; 11809723; 12200364; 17209061; 20301538; 22102271 GATA2 4171 2624 Immunodeficiency 21; Emberger syndrome; Leukemia, acute myeloid, susceptibility to; Myelodysplastic syndrome, susceptibility to AD Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Hematologic; Oncologic; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Oncologic Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Surveillance for myelodysplastic syndrome and related oncologic processes (eg, acute myeloid leukemia) may allow early diagnosis and treatment, which may reduce morbidity and mortality; In Emberger syndrome, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; HSCT has been described 295075; 21765025; 21892162; 21892158; 22147895; 22271902; 23223431; 24227816 GATA3 4172 2625 Hypoparathyroidism, sensorineural deafness, and renal dysplasia AD Pediatric Audiologic/Otolaryngologic; Endocrine; Renal Audiologic/Otolaryngologic; Endocrine; Renal Early recognition of electrolyte abnormalitities (eg, hypocalcemia) can allow prompt treatment in order to avoid severe sequelae; Individuals may also have deafness of varying ages of onset, and may benefit from early recognition and treatment of hearing impairment 10935639; 11389161; 17309062; 19248180; 9253381; 21399899; 21242646; 21834031; 21157112; 21120445 GATA4 4173 2626 Atrioventricular septal defect 4; Ventricular septal defect 1; Atrial septal defect 2 AD Pediatric Allelic with Testicular anomalies with or without congenital heart disease (AD); Tetralogy of Fallot (AD) Cardiovascular; Genitourinary Cardiovascular Individuals may present with frank, obvious congenital cardiac malformations, but more subtle presentations in individuals with variants in this gene have also been described, including valvular anomalies and arrhythmias, and surveillance (eg, with electrocardiogram and echocardiogram) may allow early detection and treatment of manifestations 12845333; 15810002; 17643447; 18055909; 18672102; 20347099; 20659440; 21110066; 21220346; 21637914; 22101736; 22552926; 22648249 GATA5 15802 140628 Congenital heart defects, multiple types, 5 AD Pediatric Cardiovascular Cardiovascular Bi-allelic variants have also been described Individuals have been described with findins including arrhythmias (atrial fibrillation), and awareness may allow prompt diagnosis and management 22483626; 22961344; 23031282; 23175127; 23295592; 25543888; 27066509; 28180938 GATA6 4174 2627 Heart defects, congenital, and other congenital anomalies; Atrial septal defect 9 AD Pediatric Allelic with Atrioventricular septal defect 5 (AD); Persistent truncus arteriosus (AD); Tetralogy of Fallot (AD) Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic Gastrointestinal In Heart defects, congenital, and other congenital anomalies, the condition may include pancreatic a/hypogenesis, and individuals may manifest neonatally with severe sequelae of endocrine and exocrine pancreatic insufficiency, and prompt detection can allow potentially beneficial management (eg, with insulin treatment and replacement of exocrine pancreatic enzymes); In Atrial septal defect 9, individuals may present with frank, obvious congenital cardiac malformations, but more subtle presentations in individuals with variants in this gene have also been described, including valvular anomalies, and surveillance (eg, with electrocardiogram and echocardiogram) may allow early detection and treatment of manifestations 19666519; 20631719; 20581743; 22158542; 22750565; 22824924; 22962692; 23020118; 23158662; 23223019; 23635550; 23639568; 24385578 GATAD1 29941 57798 Cardiomyopathy, dilated, 2B AR Adult Cardiovascular Cardiovascular Surveillance (eg, echocardiography/electocardiography), preventive measures and medical management (including ICD placement) may be helpful to decrease morbidity and mortality 21965549 GATAD2B 30778 57459 GAND syndrome (Mental retardation, autosomal dominant, 18) AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23033978; 31205050; 28077840; 30346093; 31205050; 31949314; 32688057 GATB 8849 5188 Combined oxidative phosphorylation deficiency 41 AR N/A N/A Biochemical; Cardiovascular; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30283131 GATC 25068 283459 Combined oxidative phosphorylation deficiency 42 AR N/A N/A Biochemical; Cardiovascular; Hematologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30283131 GATM 4175 2628 Fanconi renotubular syndrome 1; Cerebral creatine deficiency syndrome 3 AD/AR Pediatric Biochemical; Neurologic; Renal Biochemical; Renal In Fanconi renotubular syndrome 1, individuals manifest with renal disease, and awareness may allow prompt management to help manage sequelae, and there is some evidence that creatine supplementation may be beneficial; In Cerebral creatine deficiency syndrome 3, treatment with oral creatine has been reported to possibly increase cerebral creatine, resulting in improved cognitive development 10762163; 11555793; 12468279; 16769397; 20301745; 20682460; 22386973; 23660394; 29654216 GBA 4177 2629 Gaucher disease (types I, II, III, IIIC) AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Biochemical; Cardiovascular Variants may also contribute to neurologic conditions such as Parkinson disease Enzyme replacement (ERT) and substrate reduction therapy (SRT) is available, and can be effective in terms of hematologic, visceral, and skeletal manifestations; In addition to supportive care (which can include, for example, the need for RBC transfusions), splenectomy may be beneficial related to splenomegaly and thrombocytopenia in individuals for whom ERT/SRT is not available; BMT/HSCT has been reported in certain severe forms of disease (eg, type 3, which include neurological involvement); D409H homozygosity results in a phenotype involving specific cardiovascular manifestations, and early diagnosis and care of these manifestations may reduce morbidity and mortality 13906837; 4713569; 870871; 7363908; 7138174; 7160406; 6507325; 3732318; 3950849; 2880291; 3385740; 3342593; 3353383; 2464926; 2308952; 2378352; 2023606; 1817041; 1897529; 1333717; 8434610; 8437594; 7475546; 7500785; 8118463; 8544197; 8544959; 7701581; 7942798; 8737974; 9011805; 9040001; 10636167; 10796875; 10649495; 10682310; 10685993; 11359469; 11241475; 11486896; 12133749; 12359135; 12970647; 12752568; 12595585; 14677062; 15525722; 15669682; 15690354; 16199246; 16630170; 15813845; 15734007; 15937077; 16601874; 16790605; 17464953; 17850633; 17878420; 18338393; 18332251; 19067373; 19286695; 19858467; 19846850; 20837857; 20301446; 21502868; 22375149; 22713811; 22916340; 23363328; 23536258; 23570288; 23683771; 23647506; 31130326; 33485799 GBA2 18986 57704 Spastic paraplegia 46, autosomal recessive AR N/A N/A Genitourinary; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18332254; 23332916; 23332917 GBE1 4180 2632 Glycogen storage disease IV AR Pediatric Allelic with Polyglucosan body neuropathy, adult form (AR); Lethal pterygium syndrome, autosomal recessive (AR) Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic Biochemical; Cardiovascular In some forms of Glycogen storage disease IV, management to decrease morbidity and mortality related to cardiac sequalae may be beneficial; Liver transplant may be beneficial in some individuals 13279125; 5229990; 4502299; 284761; 6579239; 3464425; 3474393; 3162725; 1984162; 1375445; 7683169; 8437594; 8059607; 8494336; 8613547; 8830177; 9851430; 10384399; 10545044; 10449659; 10603098; 10762170; 12913206; 15452297; 15520786; 14755501; 15019703; 16007674; 16528737; 17662246; 17915577; 17994551; 18661138; 18230843; 20301758; 19813197; 20058079; 20833045; 20531024; 21917543; 22305237; 23218673 GCDH 4189 2639 Glutaric aciduria, type I AR Pediatric Biochemical; Cardiovascular; Neurologic Biochemical Early detection to allow treatment to decrease morbidity/mortality related to acute metabolic compensation, as well as dietary measures to reduce lysine oxidation and influx (eg, with low lysine diet and arginine supplementation) and increase glutaryl-CoA detoxification (eg, with carnitine supplementation) can be beneficial 1137568; 624191; 3658174; 2027453; 1951469; 8139602; 8541831; 7564239; 8552212; 8900227; 11060535; 10699052; 12473778; 12888985; 15505396; 15954035; 15985591; 16641220; 17188916; 17203377; 17478444; 17622945; 17957492; 18775269; 19260933; 20084589; 20301313; 20732827; 21031586; 21912879; 22520952; 23225040; 23395213; 23884036 GCGR 4192 2642 Mahvash disease AR Pediatric Endocrine; Oncologic Endocrine; Oncologic The condition can involve alpha-cell hyperplasia with glucagonemia, and can lead to glucagonomas and/or primitive neuroectodermal tumors, and awareness may allow early diagnosis and management of medical manifestations and neoplasms 19657311; 29702528; 30032256; 30294546; 32677665 GCH1 4193 2643 Hyperphenylalaninemia, BH4-deficient, B; Dystonia, dopa-responsive AD/AR Pediatric Biochemical; Neurologic Biochemical In Hyperphenylalaninemia, BH4-deficient, B, medical therapy (eg, BH-4, 5-HT, L-dopa) may be beneficial; In Dopa-responsive dystonia, which may not be easily clinically recognizable early, L-dopa can be effective 942621; 945938; 6734669; 3762960; 3822637; 3400489; 3041760; 2296384; 1899474; 8163996; 7874165; 7869202; 7730309; 9667588; 10208576; 10987649; 11113234; 11346370; 12084887; 12552057; 15753436; 16908750; 17111153; 20301681 GCK 4195 2645 Diabetes mellitus, permanent neonatal 1; Maturity-onset diabetes of the young, type 2; Hyperinsulinemic hypoglycemia, familial 3 AD/AR Pediatric Endocrine Endocrine Individuals with Diabetes mellitus, permanent neonatal have been described with early-onset diabetes mellitus, and recognition may allow prompt early care (eg, with rehydration and insulin), as well as decisions regarding longer-term care (eg, some patients with variants in certain genes may respond to specific medications); In Hyperinsulinemic hypoglycemia, familial, recognition may allow prompt treatment of hypoglycemia; At initial diagnosis, hypoglycemia can be corrected with IV glucose in order to prevent brain damage; Long-term management includes diazoxide, somatostatin analogs, nifedipine, glucagon, recombinant IGF-I, glucocorticoids, human growth hormone, and dietary intervention; If aggressive medical management fails or is not possible (for example, in the case of some individuals with severe AR disease), pancreatic resection may be considered; In MODY, recognition of the underlying cause of MODY may help direct specific management strategies (eg, choice of medications) 1360036; 1303265; 1545870; 1570017; 8376578; 8446612; 9435328; 9662401; 9469993; 11372010; 11916951; 14517946; 12941786; 15277402; 16965331; 17204055; 18399931; 18571549; 20301549; 20375417; 20301620 GCLC 4311 2729 Gamma-glutamylcysteine synthetase deficiency AR Pediatric Hematologic Hematologic; Pharmacogenomic Individuals have required exchange transfusion for infantile hyperbilirubinemia; Hemolysis-causing medications should be avoided; Supplementation (eg, with vitamins C or E) may be beneficial 5058793; 4852017; 2294991; 8634459; 10515893; 10733484; 12663448; 21657237 GCM2 4198 9247 Hypoparathyroidism, familial isolated, 2; Hyperparathyroidism 4 AD/AR Pediatric Endocrine; Oncologic Endocrine; Oncologic In Hypoparathyroidism, familial isolated, early recognition of electrolyte abnormalitities (eg, hypocalcemia) can allow prompt treatment in order to avoid severe sequelae; In Hyperparathyroidism 4, individuals have been described with multiple parathyroid tumors (as well as other neoplasms), and awareness may allow early diagnosis and management of these tumors and sequelae 15863676; 18583467; 19940031; 20190276; 20463099; 22066718; 23155703; 27745835 GCNT2 4204 2651 Blood group, Ii; Adult i phenotype without cataract BG/AR Pediatric Hematologic; Ophthalmologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 6858080; 3799539; 11739194; 12424189; 21912254 GCSH 4208 2653 Glycine encephalopathy AR Pediatric Biochemical; Neurologic; Ophthalmologic Biochemical There is no current effective treatment for severe disease, but children with variants associated with residual GCS enzyme activity treated aggressively early with sodium benzoate and N-methyl D-aspartate receptor site antagonists may have improved outcomes (no individuals with biallelic variants have been described to date, but there is biochemical evidence of such individuals) 6790577; 12402263; 20301531; 21470805 GDAP1 15968 54332 Charcot-Marie-Tooth disease, recessive intermediate, A; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis; Charcot-Marie-Tooth disease, axonal, type 2K; Charcot-Marie-Tooth disease, type 4A AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743579; 11743580; 12499475; 12707075; 12566285; 15805163; 17039978; 18492089; 20685671; 21753178; 22200116; 22971097 GDAP2 18010 54834 Spinocerebellar ataxia, autosomal recessive 27 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30084953 GDF1 4214 2657 Congenital heart defects, multiple types, 6; Right atrial isomerism AD/AR N/A N/A Cardiovascular; Gastrointestinal; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17924340; 20413652; 28991257 GDF11 4216 10220 Vertebral hypersegmentation and orofacial anomalies AD N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31215115 GDF2 4217 2658 Hereditary hemorrhagic telangiectasia, type 5 AD Pediatric Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Pulmonary Cardiovascular; Gastrointestinal; Hematologic; Obstetric; Pharmacogenomic; Pulmonary There are a number of surveillance/preventive/treatment based measures; These include: epistaxis treatment with humidification, lubricants, hormone therapy, anti-fibrinolytic agents, ablation, surgery, etc.; GI bleeding: iron replacement, hormonal or anti-fibrinolytic medication, surgery, etc.; Pulmonary AVM: catheter occlusion, and preventive measures such as antibiotic prophylaxis; symptomatic cerebral AVMs: surgery/embolotherapy, etc; Severe hepatic AVMs: liver transplantation if medical management fails; Specific pregnancy-related screening may be indicated; Anemia: Iron replacement or transfusion; Avoidance of certain activities and use of anticoagulant and anti-inflammatory agents (including aspirin) in the case of significant bleeding; For PAH, medical therapy (eg, prostanoids, endothelin receptor antagonists, etc.) may be beneficial, but lung transplantation may be indicated 23972370 GDF3 4218 9573 Microphthalmia, isolated 7; Microphthalmia with coloboma 6; Klippel-Feil syndrome 3, autosomal dominant AD/Digenic N/A N/A Musculoskeletal; Ophthalmologic General Microphthalmia, isolated 4; Microphthalmia with coloboma 6, digenic; Multiple synostoses syndrome 4; Klippel-Feil syndrome 1, autosomal dominant; Leber congenital amaurosis 17 Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15241163; 19864492 GDF5 4220 8200 Acromesomelic dysplasia, Hunter-Thompson type; Du Pan syndrome (Fibular hypoplasia and complex brachydactyly); Multiple synostoses syndrome 2; Chondrodysplasia, Grebe type; Symphalangism, proximal 1B; Brachydactyly, type A1, C; Brachydactyly, type A2; Brachydactyly, type C AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13953230; 14159881; 4850715; 964999; 2624264; 2703235; 2363425; 8954778; 8589725; 9288098; 9489798; 12357473; 12121354; 12567410; 14735582; 16127465; 16222676; 16532400; 16014698; 16957682; 16892395; 17384641; 18629880; 18283415; 19956691; 20683927 GDF6 4221 392255 Microphthalmia, isolated 4; Microphthalmia, isolated, with coloboma 6; Multiple synostoses syndrome 4; Coloboma, ocular; Klippel-Feil syndrome 1, autosomal dominant; Leber congenital amaurosis 17 AD/AR/Digenic N/A N/A Audiologic/Otolaryngologic; Musculoskeletal; Ophthalmologic General Digenic inheritance (with GDF3) has been reported Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8533765; 17236135; 18425797; 19129173; 19864492; 21070663; 23307924; 26643732; 29130651 GDF9 4224 2661 Premature ovarian failure 14 AR Pediatric Endocrine Endocrine Heterozygous variants have also been described as potentially contributing to the phenotype The condition has been described as manifesting with primary amenorrhea, and medical management (treatment with conjugated estrogens followed by progesterone replacement in the first 12 days of the month) has been reported as resulting in complete breast development and normal menstrual cycles 27603904 GDI1 4226 2664 Mental retardation, X-linked 41 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8826463; 9106537; 9668174; 9620768; 22002931 GDNF 4232 2668 Central hypoventilation syndrome; Hirschsprung disease, susceptibility to, 3 AD Pediatric Gastrointestinal; Neurologic Gastrointestinal; Neurologic In Central hypoventilation syndrome, early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality; In conditions that may involve Hirschsprung disease, recognition of potential GI anomalies (eg, aganglionosis) may allow prompt recognition and treatment 8896568; 8968758; 8896569; 9497256; 11973622; 11823451; 22729463 GEMIN4 15717 50628 Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities AR Pediatric Neurologic; Ophthalmologic; Renal Renal The condition can include renal manifestations, including hydronephrosis, renal stones, nephrocalcinosis, and secondary hypertension, and awareness may allow early management of renal-related manifestations 25558065; 27878435; 30237576 GEMIN5 20043 25929 Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33963192 GFAP 4235 2670 Alexander disease AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15409268; 13665382; 11138011; 11567214; 12034785; 12447932; 12034796; 14557587; 12975300; 15732097; 15732098; 16505300; 17894839; 17438228; 20301351; 21822933; 21917775; 21987397; 22118268; 22198646; 22488673; 22619055; 23254569; 23364391; 23634874 GFER 4236 2671 Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay AR N/A N/A Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19409522 GFI1 4237 2672 Neutropenia, severe congenital, 2 autosomal dominant; Neutropenia, nonimmune chronic idiopathic, of adults AD Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; The condition may predispose to leukemia, and thus surveillance for hematologic anomalies may allow early diagnosis and treatment 1810106; 12778173; 12963840; 20560965 GFI1B 4238 8328 Bleeding disorder, platelet-type, 17 AD Pediatric Hematologic Hematologic Individuals have increased bleeding tendency (of variable severity), and awareness may allow preventive measures and early management of bleeding complications 5681484; 1065298; 23927492; 24325358 GFM1 13780 85476 Combined oxidative phosphorylation deficiency 1 AR N/A N/A Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15537906; 17160893; 21119709 GFM2 29682 84340 Combined oxidative phosphorylation deficiency 39 AR N/A N/A Biochemical; Neurologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22700954; 26016410; 29075935 GFPT1 4241 2673 Myasthenic syndrome, congenital 12 AR Pediatric Musculoskeletal; Neurologic Musculoskeletal; Pharmacogenomic Acetylcholinesterase inhibitors have been shown to result in a favorable treatment response; Avoidance of certain agents involved in neuromuscular transmission is indicated (eg, ciprofloxacin, chloroquine, lithium, phenytoin, beta-blockers, procainamide); Additional neurologic monitoring in pregnancy may be beneficial 8664562; 12467753; 21310273; 23108489 GGCX 4247 2677 Vitamin K-dependent clotting factors, combined deficiency of, 1; Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency AD/AR/Digenic Pediatric Cardiovascular; Dermatologic; Hematologic; Musculoskeletal Cardiovascular; Hematologic Digenic inheritance (with ABCC6) has been reported in Pseudoxanthoma elasticum In Vitamin K-dependent clotting factors, combined deficiency of, 1, vitamin K administration can be effective; In Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency, surveillance and prompt treatment of bleeding diatheses, as well as vascular malformations, may reduce morbidity and mortality 5936414; 426915; 7085873; 9845520; 17110937; 18800149; 19116367 GGT1 4250 2678 Glutathionuria AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29483667 GH1 4261 2688 Isolated growth hormone deficiency, type IA; Isolated growth hormone deficiency, type 1B; Isolated growth hormone deficiency, type II; Kowarski syndrome AD/AR Pediatric Endocrine Endocrine Some individuals respond well to exogenous GH treatment, and benefits may be increased with early diagnosis and treatment 7714096; 8530604; 9076339; 9024229; 9024235; 8552145; 9276733; 9435425; 10678654; 11443201; 12915652; 12655557; 15713716; 16060904; 15671105; 17785701; 18554279; 17925337; 20852587 GHR 4263 2690 Growth hormone insensitivity syndrome (Laron syndrome) AD/AR Pediatric Endocrine Endocrine Medical treatment (eg, with recombinant human IGF1) can be beneficial 5707789; 4470894; 1349669; 8488849; 7565946; 8784089; 9140387; 9024266; 9360502; 9851797; 11297575; 11468686; 12679461; 15001620; 17148568; 18404972; 18073295; 19789204; 20583548; 19812236; 20606392; 20962506; 21325617; 21396571; 21900382; 22117696; 22423513; 22587301; 23006617 GHRHR 4266 2692 Isolated growth hormone deficiency, type IV AR Pediatric Endocrine Endocrine Combined treatment of GH and GNRHa can be effective in increasing final height, even in the case of advanced bone age and pubertal stage, though consideration related to cardiovascular-related treatment effects may be beneficial 8528260; 11443201; 17925337; 19733620; 21274317; 21044116; 22423511; 21816782; 21292919; 22416078 GHSR 4267 2693 Short stature AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16511605; 19789204; 21646290 GIGYF2 11960 26058 Parkinson disease, autosomal dominant, 11 AD Adult Neurologic Neurologic The association with disease is controversial Response to levodopa has been documented 18358451; 18923002; 19250854; 19279319; 19449032; 19482505; 19845746; 19906271; 20004041; 20044296; 20060621; 20178831; 20641165; 20816920; 22115759 GINS1 28980 9837 Immunodeficiency 55 AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Dermatologic Allergy/Immunology/Infectious The condition can include early-onset, severe, and recurrent infections, as well as other immunologic sequelae, and awareness may allow antiinfectious prophylaxis and early and aggressive treatment of infections 14702466; 28414293 GIPC1 1226 10755 Oculopharyngodistal myopathy 2 AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32413282 GIPC3 18183 126326 Deafness, autosomal recessive 15 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 9286457; 9106521; 17690910; 21326233; 21660509; 23226338; 23510777 GJA1 4274 2697 Oculodentodigital dysplasia AD Pediatric Allelic with Hypoplastic left heart syndrome 1 (AD); Syndactyly, type III (AD); Oculodentodigital dysplasia, autosomal recessive (AR); Atrioventricular septal defect 3 (AR); Erythrokeratodermia variabilis et progressiva 3 (AD); Palmoplantar keratoderma with congenital alopecia (AD); Craniometaphyseal dysplasia, autosomal recessive (AR) Cardiovascular; Craniofacial; Dental; Dermatologic; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular The conditions can involve multiple congenital anomalies Individuals with cardiac arrhythmias have been reported, and surveillance (eg, with EKG) may allow early detection and treatment 2157843; 7815444; 11470490; 12457340; 15108203; 14974090; 14729836; 14981729; 15551259; 15637728; 16709485; 16816024; 17256797; 18412120; 19338053; 21670345; 22179534; 22214631; 23951358; 25168385; 25398053 GJA3 4277 2700 Cataract 14, multiple types AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10205266; 10746562; 15286166; 22312188; 22550389; 22876138; 23592915; 23734083 GJA5 4279 2702 Atrial fibrillation, familial 11; Atrial standstill, digenic AD/Digenic Adult Cardiovascular Cardiovascular Digenic inheritance (with SCN5A) has been described Surveillance (eg, with echocardiography/electrocardiography) and medical/surgical intervention related to arrhythmias and associated sequelae may be beneficial 12522116; 16790700; 21076161; 22247482 GJA8 4281 2703 Cataract 1, multiple types AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14059288; 9497259; 10480374; 11846744; 14627691; 16604058; 18006672; 19756179; 21720542; 20019893; 20597646; 20806042; 21921990 GJB1 4283 2705 Charcot-Marie-Tooth neuropathy, X-linked dominant, 1 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8266101; 10487913; 17100997; 17353473; 21254193; 21504505; 21692908; 21922480; 21692908; 22483671; 22577229 GJB2 4284 2706 Deafness, autosomal recessive 1A; Deafness, digenic; Hystrix-like ichthyosis with deafness; Deafness, autosomal dominant 3A; Bart-Pumphrey syndrome; Keratoderma, palmoplantar, with deafness; Vohwinkel syndrome; Keratitis-icthyosis-deafness syndrome AD/AR/Digenic Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Oncologic; Ophthalmologic Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Oncologic In nonsyndromic deafness, onset of AD disease can be pre or postlingual; In syndromic disease, although skin and other findings may be obvious in some individuals, the syndromic combination of features may not be as readily appreciated as being related to hearing impairment; Digenic inheritance (with GJB3, GJB6) has been described Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In certain conditions (eg, KID syndrome), infectious and malignant complications may benefit from surveillance leading to microbial prophylaxis and early and aggressive treatment of infections and early detection and treatment of malignancy 6015974; 1532426; 8010352; 7748756; 9139825; 9529365; 9620796; 10218527; 10369869; 10633135; 10807696; 11298683; 11807148; 12047643; 11960582; 11912510; 11889383; 12372058; 12072059; 11918723; 12560944; 14694360; 15150777; 15482471; 14700667; 16222667; 16380907; 15994881; 15633193; 15691545; 15996214; 16840571; 17041943; 17330861; 993581; 17041943; 19050930; 18843290; 20815033; 20412116 GJB3 4285 2707 Deafness, autosomal recessive; Deafness, autosomal dominant, with peripheral neuropathy; Deafness digenic AD/Digenic Pediatric Allelic with Erythrokeratodermia variabilis et progressiva 1 (AD/AR); Deafness, autosomal dominant 2B (AD) Audiologic/Otolaryngologic; Dermatologic; Neurologic Audiologic/Otolaryngologic Digenic inheritance (with GJB2) has been described Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 1828175; 9843209; 9843210; 10594760; 10798362; 11175305; 12019212; 12452892; 19050930 GJB4 4286 127534 Erythrokeratodermia variabilis et progressiva 2 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 148984; 11017804; 12648223; 19291775; 21564177; 22266302; 23037955 GJB6 4288 10804 Deafness, autosomal recessive 1B; Deafness, digenic AR/Digenic Pediatric Allelic with Deafness, autosomal dominant 3B (AD); Ectodermal dysplasia, hidrotic (Clouston syndrome) (AD) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dental; Dermatologic Audiologic/Otolaryngologic Digenic inheritance (eg, with GJB2) has been described Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 10471490; 11017065; 11807148; 11896458; 15150777; 15994881; 17041943; 18324688; 21465647 GJC2 17494 57165 Lymphedema malformation 3; Spastic paraplegia 44, autosomal recessive; Leukodystrophy, hypomyelinating, 2 AD/AR N/A N/A Cardiovascular; Dermatologic; Neurologic General Individuals with Lymphedema have been described with recurrent skin infections Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15192806; 16969684; 18094336; 19056803; 20513814; 20537300; 21266381; 21959080; 22610664; 22669416; 23143715; 24374284 GK 4289 2710 Glycerol kinase deficiency XL Pediatric Biochemical; Neurologic Biochemical Specific dietary measures (eg, fat/glycerol-restricted diet) can be beneficial 6325658; 8651297; 9719371; 10736265; 11032329; 18607276; 21542762; 23009783 GLA 4296 2717 Fabry disease; Fabry disease, cardiac variant XL Pediatric Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Dermatologic; Neurologic; Ophthalmologic; Renal Biochemical; Cardiovascular; Renal In individuals with Fabry disease, enzyme therapy is available; Both males and females with variants can suffer from significant multisystemic disease manifestations (including cardiovascular, cerebrovascular, and renal disease) and require monitoring and treatment, which can reduce morbidity; Individuals with Cardiac variant Fabry disease can have adult-onset left ventricular hypertrophy with or without renal failure, and early diagnosis and medical management may be beneficial 5411915; 4914726; 5466114; 6294821; 6283080; 3107860; 2539398; 2120125; 1645238; 1846223; 8395937; 7879606; 7817917; 7596372; 8807334; 8738659; 11105184; 10618424; 11694547; 11179018; 11732485; 11530143; 11386930; 11804208; 11889412; 12911529; 12519371; 15253767; 15162124; 15154115; 16298216; 16533976; 16926253; 16980809; 17371887; 17256799; 17362993; 17224688; 18023222; 19473999; 19318041; 19843486; 19853240; 19959221; 19965549; 19745746; 20301469; 21502868; 22431073; 22450713; 22498845; 22704481; 22731890; 22878429; 22880956; 22881192; 22880956; 22898981; 22963910; 22998007; 23040658; 23089251; 23094092; 23703683; 31860127 GLB1 4298 2720 Mucopolysaccharidosis type IVB (Morquio syndrome B); GM1-gangliosidosis, type I; GM1-gangliosidosis, type II; GM1-gangliosidosis, type III AR N/A N/A Biochemical; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14209687; 14261015; 4227214; 4173446; 4231206; 4243740; 5541675; 4650864; 5031983; 4143049; 4420522; 4139552; 131309; 62026; 404231; 416929; 99363; 121869; 6777095; 6791574; 6791575; 7173264; 3926630; 3917501; 1909089; 1928092; 1907800; 1336295; 1353343; 8198123; 7586649; 10841810; 10737981; 11511921; 12644936; 15986423; 16466959; 16941474; 17309651; 18524657; 19472408; 20175788; 21204790; 21497194; 22234367; 23046582 GLDC 4313 2731 Glycine encephalopathy AR Pediatric Biochemical; Neurologic; Ophthalmologic Biochemical Treatment may be less effective for individuals with severe disease; however, aggressive early treatment with sodium benzoate and N-methyl D-aspartate receptor site antagonists in individuals with variants associated with residual GCS enzyme activity have been reported to result in improved outcomes 10873393; 12402263; 15077252; 15236413; 15851735; 16151895; 16404748; 16450403; 17361008; 20301531; 20933183; 21411353; 23349517 GLDN 29514 342035 Lethal congenital contracture syndrome 11 AR N/A N/A Neurologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27616481 GLE1 4315 2733 Congenital arthrogryposis with anterior horn cell disease; Lethal congenital contracture syndrome 1 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7966188; 7897624; 18204449; 30239721 GLI1 4317 2735 Polydactyly, postaxial, type A8; Polydactyly, preaxial I AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28973407; 30620395 GLI2 4318 2736 Culler-Jones syndrome AD Pediatric Allelic with Holoprosencephaly 9 (AD) Craniofacial; Endocrine; Musculoskeletal; Neurologic Endocrine While initially reported (and named) as associated with holoprosencephaly the more classic presentation involves (sometimes subclinical) endocrinological manifestations, including treatable deficiency, such as of thyroid hormone and growth hormone, and awareness may allow endocrine-based testing and management to help amelioriate these manifestations 14581620; 15994174; 17096318; 20685856; 22967285; 23112757; 23304807; 23408573; 24744436; 30629636 GLI3 4319 2737 Pallister-Hall syndrome AD Pediatric Allelic with Acrocallosal syndrome (AD); Grieg cephalopolysndactyly syndrome (AD); Polydactyly, postaxial, type A1 (AD); Polydactyly, preaxial, type IV (AD); Polydactyly, postaxial, types A1 and B (AD) Craniofacial; Endocrine; Musculoskeletal; Neurologic Endocrine Urgent treatment for endocrine abnormalities may be required; Surgical interventions related to hypothalamic hamartoma may be indicated 4317883; 7211952; 6295159; 6641002; 2596511; 1650914; 9054938; 9042919; 9302279; 10441570; 10945658; 10678662; 12794692; 14608643; 15811011; 15739154; 18000979; 18435847; 20301619; 20301638; 20503312; 20583172; 20672375; 21108399; 21320477; 21326280; 22428873; 23633388; 24736735 GLIS2 29450 84662 Nephronophthisis 7 AR N/A N/A Renal General Renal transplantation has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17618285; 23559409 GLIS3 28510 169792 Diabetes mellitus, neonatal, with congenital hypothyroidism AR Pediatric Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal Endocrine Prompt treatment (eg, of ketoacidosis and dehydration) can avoid morbidity; Treatment of congenital hypothyroidism can improve outcome 12966531; 16715098 GLMN 14373 11146 Glomuvenous malformations AD N/A N/A Cardiovascular; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11845407; 23375657 GLRA1 4326 2741 Hyperekplexia 1 AD/AR Pediatric Neurologic Neurologic Neonates are at risk of sudden death from apnea/aspiration, and surveillance, as well as primary prevention with medical treatments (eg, clonazepam) may be beneficial 1334371; 8298642; 7881416; 11104232; 8571969; 16832093; 20301437 GLRB 4329 2743 Hyperekplexia 2 AR Pediatric Neurologic Neurologic Neonates are at risk of sudden death from apnea/aspiration, and surveillance, as well as primary prevention with medical treatments (eg, clonazepam) may be beneficial 11929858; 21391991; 20301437 GLRX5 20134 51218 Anemia, sideroblastic 3, pyridoxine-refractory AR Pediatric Allelic with Spasticity, childhood-onset, with hyperglycinemia (AR) Biochemical; Hematologic; Neurologic Hematologic Individuals with Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive have been reported who required RBC transfusions, as well as management with folate and iron chelation 17485548; 24334290; 30660387 GLS 4331 2744 Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development; Epileptic encephalopathy, early infantile, 71; Global developmental delay, progressive ataxia, and elevated glutamine AD/AR N/A N/A Biochemical; Dermatologic; Neurologic; Ophthalmologic General Global developmental delay, progressive ataxia, and elevated glutamine is caused by triplet repeat expansion upstream of the GLS gene Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30239721; 30575854; 30970188 GLUD1 4335 2746 Hyperinsulinemic hypoglycemia, familial 6; Hyperammonemia-hyperinsulinism AD Pediatric Biochemical; Endocrine Biochemical; Endocrine At initial diagnosis, hypoglycemia can be corrected with IV glucose in order to prevent brain damage; Long-term management includes diazoxide, somatostatin analogs, nifedipine, glucagon, recombinant IGF-I, glucocorticoids, human growth hormone, and dietary intervention (including with leucine restrictions in some recessive forms of disease); If aggressive medical management fails or is not possible, pancreatic resection may be considered 9843361; 9571255; 9469993; 10636977; 10871207; 11518822; 11241047; 11297618; 11214910; 19046187; 20857847; 20301549; 22106762; 21932603; 22759688 GLUL 4341 2752 Glutamine deficiency, congenital AR Pediatric Biochemical; Neurologic Biochemical Supplementation with glutamine has been reported as resulting in clinical (measured by alertness) and electroencephalogram-documented improvements 16267323; 21353613; 22830360 GLYCTK 24247 132158 D-glyceric aciduria AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4599249; 2537226; 20949620 GM2A 4367 2760 GM2-gangliosidosis, AB variant AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5135907; 10364519; 11339652 GMNN 17493 51053 Meier-Gorlin syndrome 6 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26637980 GMPPA 22923 29926 Alacrima, achalasia, and mental retardation syndrome AR N/A N/A Audiologic/Otolaryngologic; Dermatologic; Gastrointestinal; Neurologic; Ophthalmologic General Onset and severity of hearing impairment is unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24035193 GMPPB 22932 29925 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14; Limb-girdle muscular dystrophy-dystroglycanopathy, type B, 14; Limb-girdle muscular dystrophy-dystroglycanopathy, type C, 14 AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular Cardiovascular complications, including long QT syndrome and cardiomyopathy, have been described, and awareness may allow surveillance and prompt management 23768512 GNA11 4379 2767 Hypocalcemia, autosomal dominant 2; Hypocalciuric hypercalcemia, familial, type II AD Pediatric Endocrine Endocrine In Hypocalcemia, early recognition of electrolyte abnormalitities (eg, hypocalcemia) can allow prompt appropriate management in order to avoid and/or promptly treat severe sequelae, which can include hypocalcemic seizures; In Hypocalciuric hypercalcemia, accurate diagnosis may be important in order to decrease the use of unhelpful therapies 6278146; 23782177; 23802516; 23802536; 24823460 GNAI3 4387 2773 Auriculocondylar syndrome 1 AD N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22560091; 23315542 GNAL 4388 2774 Dystonia 25 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23222958 GNAO1 4389 2775 Developmental and epileptic encephalopathy 17; Neurodevelopmental disorder with involuntary movements AD Pediatric Allelic with Developmental and epileptic encephalopathy 17 (AD) Neurologic Neurologic In Neurodevelopmental disorder with involuntary movements (NEDIM), specific medications (eg, topiramate) have been reported in some individuals as beneficial for treatment of the movement disorder 23993195; 25966631; 26060304; 27068059; 27625011; 27916449; 28357411 GNAS 4392 2778 Pseudohypoparathyroidism, type IA; Pseudohypoparathyroidism, type IB; Pseudohypoparathyroidism, type IC; Progressive osseous heteroplasia; McCune-Albright syndrome AD Pediatric Dermatologic; Endocrine; Musculoskeletal; Oncologic; Renal Endocrine; Oncologic; Renal Mosaic variants have been described; PPHP occurs with paternal inheritance In Pseudohypoparathyroidism, medical treatment (eg, with calcium and vitamin D therapy) of electrolyte abnormalities and related complications such as osteitis fibrosa cystica can be effective, and complications; Surveillance and early treatment of endocrinological manifestations (eg, hypothyroidism, hypogonadism) can be beneficial; In McCune-Albright syndrome, medical (eg, related to estrogen production, hyperthyroidism, growth hormone production) and surgical (eg, to treat adrenal pathology, hyperthyroidism) treatment of endocrinopathies may be beneficial, and surveillance and early and specific treatment for manifestations such as a number of types of neoplasms, including GH-producing tumors (eg, with long-acting octreotide, GHR antagonists) can be beneficial, as well as surveillance for and treatment of Cushing syndrome (some patients require adrenalectomy) 13005676; 5906056; 1083395; 198661; 219790; 431133; 6265935; 3126297; 2829196; 2273209; 2109828; 3093862; 2122458; 1955519; 1944469; 1400888; 1621772; 1424186; 1594625; 1346061; 8421479; 7980957; 8126048; 8126161; 7739708; 7671486; 9226216; 9506752; 0614538; 10356155; 10190480; 11073544; 10646121; 11067869; 11095461; 10998448; 11600516; 11406605; 11297617; 11583302; 11397863; 11029463; 12414879; 12024004; 12407707; 11788646; 11784876; 14561710; 12605446; 12727968; 12858292; 14557424; 12624854; 15001590; 15126527; 15711092; 16060910; 15537666; 16984995; 17405850; 17651445; 18553568; 18416659; 18397987; 20480732; 19858129; 21816789; 21488135; 21357941; 22640971 GNAT1 4393 2779 Night blindness, congenital stationary, autosomal dominant 3; Night blindness, congenital stationary, autosomal recessive, 1G AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8673138; 22190596 GNAT2 4394 2780 Achromatopsia 4 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12205108; 12077706; 15557429; 21107338 GNB1 4396 2782 Mental retardation, autosomal dominant 42 AD N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27108799 GNB3 4400 2784 Night blindness, congenital stationary, type 1H AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27063057 GNB4 20731 59345 Charcot-Marie-Tooth disease, dominant intermediate F AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20627571; 23434117 GNB5 4401 10681 Intellectual developmental disorder with cardiac arrhythmia (IDDCA); Language delay and attention deficit-hyperactivity disorder/cognitive impairment with or without cardiac arrhythmia (LADCI) AR Pediatric Cardiovascular; Neurologic Cardiovascular Among other findings, individuals have been described with cardiac abnormalities, including sick sinus syndrome with bradycardia, escape beats, and other arrhythmias, and awareness may allow early diagnosis and management such as via pacemaker placement 27523599; 27677260 GNE 23657 10020 Sialuria, French type ; Nonaka myopathy; Inclusion body myopathy, autosomal recessive AD/AR N/A N/A Biochemical; Gastrointestinal; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7252518; 2443758; 2808337; 1779656; 8439453; 10330343; 11528398; 11486897; 11326336; 12473780; 11916006; 12473753; 12177386; 12473769; 16372135; 17718674; 20059379; 20175955; 20300792; 20301343; 20301439; 20346669; 21131200; 21708040; 22196754; 22507750; 22883483; 23127962; 24685570; 24796702 GNMT 4415 27232 Glycine N-methyltransferase deficiency AR N/A N/A Biochemical; Gastrointestinal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11596649; 11810299 GNPAT 4416 8443 Rhizomelic chondrodysplasia punctata, rhizomelic, type 2 AR N/A N/A Biochemical; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1405476; 8466247; 7530787; 7541833; 9536089; 20583171; 21990100 GNPTAB 29670 79158 Mucolipidosis III alpha/beta (Pseudo-Hurler polydstrophy); Mucolipidosis II alpha/beta (I-cell disease) AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic General Bisphosphonate therapy may be beneficial for bone pain; The conditions may include severe cardiac manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4958870; 4247489; 4327936; 6461005; 6309902; 3003148; 3001079; 7628121; 12705498; 16116615; 15633164; 16094673; 16630736; 19197337; 19659762; 20301728; 21416587; 22162509; 22495880 GNPTG 23026 84572 Mucolipidosis III gamma AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal General The condition may include severe cardiac manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10712439; 15532026; 19370764; 19659762; 20034096; 20951619; 21792934 GNRH1 4419 2796 Hypogonadotropic hypogonadism 12 with or without anosmia AR/Digenic Pediatric Endocrine; Genitourinary; Neurologic Endocrine Digenic inheritance (with NR0B1) has been reported; In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 19535795; 19567835; 20301509; 20389089; 20887715; 21722705 GNRHR 4421 2798 Hypogonadotropic hypogonadism 7 with or without anosmia; Hypogonadotropic hypogonadism 23 with or without anosmia AD/AR/Digenic Pediatric Endocrine; Genitourinary Endocrine Digenic inheritance (with FGFR1) has been reported In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 13061573; 9371856; 10690855; 11397842; 17235395; 20301455; 20301509; 22035731; 22724017 GNS 4422 2799 Mucopolysaccharidosis IIID (Sanfilippo syndrome D) AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6450420; 12624138; 12573255; 17998446; 19650410; 20232353 GORAB 25676 92344 Geroderma osteodysplasticum AR N/A N/A Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 631850; 474638; 3236370; 8213917; 8723088; 9018419; 18997784; 18348262; 19681135; 21204221 GOSR2 4431 9570 Epilepsy, progessive myoclonic 6 AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21549339; 23449775; 24458321 GOT2 4433 2806 Developmental and epileptic encephalopathy 82 AR Pediatric Biochemical; Neurologic Neurologic The condition can involve early-onset metabolic encephalopathy, and treatment with combined pyridoxine and serine has been described asresulting in improvement in seizures and mild developmental progress 31422819 GP1BA 4439 2811 Bernard-Soulier syndrome, type A2; Bernard-Soulier syndrome, type A1; Pseudo-von Willebrand disease AD/AR Pediatric Hematologic Hematologic; Pharmacogenomic Preventive measures (eg, in the case of surgery) and treatment of bleeding episodes can be beneficial; Specific medications (eg, certain anesthetics) that interfere with platelet function should be avoided 18116504; 14081293; 6019024; 6286015; 6798442; 6333901; 2308962; 2052556; 1901273; 1730088; 8384898; 9616133; 11222377; 14711733; 21173099; 22102188; 23014764 GP1BB 4440 2812 Bernard-Soulier syndrome; Giant platelet disorder, isolated AR Pediatric Hematologic Hematologic; Pharmacogenomic Preventive measures (eg, in the case of surgery) and treatment of bleeding episodes can be beneficial; Specific medications (eg, certain anesthetics) that interfere with platelet function should be avoided 18116504; 14081293; 6019024; 1901273; 8703016; 9116284; 9616133; 21173099; 21800012; 22102188 GP6 14388 51206 Bleeding disorder, platelet-type, 11 AR Pediatric Hematologic Hematologic Individuals may demonstrate a bleeding diathesis (including postraumatic/postsurgical), and surveillance and prompt treatment of bleeding episodes may reduce morbidity 19549989; 19552682 GP9 4444 2815 Bernard-Soulier syndrome, type C AR Pediatric Hematologic Hematologic Preventive measures (eg, in the case of surgery) and treatment of bleeding episodes can be beneficial; Specific medications (eg, certain anesthetics) that interfere with platelet function should be avoided 18116504; 14081293; 6019024; 1901273; 8481514; 9616133; 16268478; 17109744; 21173099; 21699652 GPAA1 4446 8733 Glycosylphosphatidylinositol biosynthesis defect 15 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29100095 GPC3 4451 2719 Simpson-Golabi-Behmel syndrome, type 1 XL Pediatric Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Cardiovascular; Oncologic The condition may involve multiple congenital anomalies The disorder, which can include certain types of tumors, should be clinically recognizable, but surveillance for neoplasms may allow early diagnosis and treatment, which may ameliorate morbidity and mortality; Awareness of the risk of cardiac sequelae, which can include anatomic anomalies and dysrhythmias, may allow prompt detection and management 1227524; 6490008; 6538755; 3177455; 1479609; 7909248; 8589713; 9950367; 10232747; 11477610; 16158429; 17850639; 17603795; 18203194; 2018065; 20301398; 20950395; 21434539; 21362501; 22807161; 23463737; 23606591 GPC4 4452 2239 Keipert syndrome (Nasodigitoacoustic syndrome) XL Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic Audiologic/Otolaryngologic; Cardiovascular In affected individuals, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with pulmonic stenosis (among other features), and awareness may allow prompt diagnosis and management 30982611 GPC6 4454 10082 Omodysplasia 1 AR N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19481194 GPD1 4455 2819 Hypertriglyceridemia, transient infantile AR Pediatric Gastrointestinal Gastrointestinal Individuals may present with failure to thrive and other sequelae of disease, and dietary management (with high-calorie, low-fat diet) has been described as beneficial 22226083; 24549054 GPD1L 28956 23171 Brugada syndrome 2 AD Pediatric Cardiovascular Cardiovascular; Pharmacogenomic Surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever 11839626; 17967977; 17967976 GPHN 15465 10243 Hyperekplexia, autosomal dominant; Molybdenum cofactor deficiency, type C AD/AR N/A N/A Biochemical; Musculoskeletal; Neurologic; Ophthalmologic General In Hyperekplexia, autosomal dominant, evidence for pathogenicity is unclear (though multiple medical treatments, including clonazepam may be beneficial) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11095995; 12684523; 20301437; 21031595; 22040219 GPI 4458 2821 Hemolytic anemia, nonspherocytic due to glucose phosphate isomerase deficiency AD Pediatric Hematologic Hematologic; Pharmacogenomic Anemia may be ameliorated by splenectomy, and it may be beneficial to avoid agents (or provide monitoring if such agents are unavoidable) that may precipitate hemolytic anemia 5672849; 469896; 3796702; 10916680; 17041899; 20516363; 22782259 GPIHBP1 24945 338328 Hyperlipoproteinemia, type ID AR Pediatric Cardiovascular; Gastrointestinal Cardiovascular; Gastrointestinal Individuals have been described with severe chylomicronemia/hypertriglyceridemia, and dietary measures (eg, low fat diet) have been described as beneficial related to sequelae such as pancreatitis and colitis, as well as other cardiovascular manifestations 17883852; 19304573; 20026666; 20124439; 21816778; 22239554; 24614124; 24847059 GPNMB 4462 10457 Amyloidosis, primary, localized cutaneous, 3 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19416385; 29336782 GPR101 14963 83550 Pituitary adenoma, growth hormone secreting, 2 XL Pediatric Endocrine Endocrine The condition can involve microduplications including the gene Surveillance and/or awareness of cancer risk may allow early diagnosis of pituitary tumors (as well as related manifestations, such as hypertension, hypogonadism, diabetes mellitus, and osteoporosis), which could potentially be beneficial to allow early medical (eg, with somatostatin analogs, growth hormone receptor antagonists, dopamine agonists) or surgical treatment; Surveillance post-treatment may also be beneficial to detect recurrence/new adenomas 25470569; 25806920 GPR143 20145 4935 Nystagmus 6, congenital, X-linked; Ocular albinism, type I XL N/A N/A Dermatologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7915878; 7647783; 8634705; 9887374; 9529334; 11214907; 11520764; 11793467; 17516023; 18523664; 19123159; 19390656; 19604113; 19610097; 20301517; 20649618; 21274678; 21348135; 21423867; 22916221 GPR179 31371 440435 Night blindness, congenital stationary, type 1E AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22325361; 22325362; 23714322 GPR68 4519 8111 Amelogenesis imperfecta, hypomaturation type, IIA6 AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27693231 GPR88 4539 54112 Chorea, childhood-onset, with psychomotor retardation AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27123486 GPRASP2 25169 114928 Deafness, X-linked, 7 XL Pediatric Audiologic/Otolaryngologic; Craniofacial Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 28096187 GPSM2 29501 29899 Chudley-McCullough syndrome AR Pediatric Audiologic/Otolaryngologic; Neurologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 20602914; 20602914 GPT2 18062 84706 Neurodevelopmental disorder with spastic paraplegia and/or microcephaly AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25758935 GPX4 4556 2879 Sedaghatian-type spondylometaphyseal dysplasia AR N/A N/A Cardiovascular; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22529034; 24706940 GRAP 4562 10750 Deafness, autosomal recessive, 114 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 30610177 GREB1L 31042 80000 Renal hypodysplasia/aplasia 3; Deafness, autosomal dominant 80 AD N/A N/A Audiologic/Otolaryngologic; Renal Audiologic/Otolaryngologic; Renal Individuals with Renal hypodysplasia/aplasia 3 may manifest with subtle findings such as vesicoureteral reflux, and awareness may allow prophylactic measures to preserve renal function; In Deafness, autosomal dominant 80, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 28739660; 29100090; 29100091; 29955957; 32585897 GREM1 2001 26585 Polyposis syndrome, mixed hereditary 1 AD Pediatric Oncologic Oncologic The condition has been reported as associated with a duplication including the 3' end of the SCG5 gene upstream of GREM1 Individuals are at risk of colonic neoplasms including adenomas and colorectal carcinomas (with polyps detected by 18 years of age), and awareness may allow surveillance and prompt treatment, which may be beneficial 22561515; 26493165 ; 26947005 GREM2 17655 64388 Tooth agenesis, selective, 9 AD N/A N/A Dental; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26416033 GRHL2 2799 79977 Cornealy dystrophy, posterior polymorphous, 4; Ectodermal dysplasia/short stature syndrome AD/AR Pediatric Allelic with Deafness, autosomal dominant 28 (AD) Audiologic/Otolaryngologic; Dental; Dermatologic; Musculoskeletal; Ophthalmologic Audiologic/Otolaryngologic; Ophthalmologic For Corneal dystrophy, posterior polymorphous, 4, individuals may have secondary glaucoma, and awareness may allow surveillance, prompt diagnosis, and management to prevent visual loss; For Ectodermal dysplasia/short stature syndrome, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12393799; 25152456; 29499165 GRHL3 25839 57822 van der Woude syndrome 2 AD N/A N/A Craniofacial; Dental; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24360809 GRHPR 4570 9380 Hyperoxaluria, primary, type II AR Pediatric Biochemical; Renal Renal Fluid intake and medical management (eg, orthophosphate, potassium citrate, magnesium) to prevent calcium oxalate crystallization can be effective; Temporary dialysis for ESRD, followed by transplantation may be required; Surveillance of renal function and related parameters may be effective; Dehydration and excessive intake of oxalate-rich foods should be avoided 4321474; 2040928; 7987654; 9243228; 10484776; 11030416; 11518794; 11156702; 11135054; 11477177; 12185464; 14635115; 12897114; 15327387; 16756993; 17510093; 19296982; 20301742; 24116921 GRIA2 4572 2891 Neurodevelopmental disorder with language impairment and behavioral abnormalities AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31300657 GRIA3 4573 2892 Mental retardation, X-linked, syndromic, Wu type XL N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17568425; 17989220; 19449417; 22124977 GRIA4 4574 2893 Neurodevelopmental disorder with or without seizures and gait abnormalities AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29220673 GRID2 4576 2895 Spinocerebellar ataxia, autosomal recessive 18 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23611888; 24078737 GRIK2 4580 2898 Mental retardation, autosomal recessive 6 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17120046; 17847003; 25039795 GRIK4 4582 2900 Response to antidepressant treatment with citalopram AD Pediatric General Pharmacogenomic The choice of medications may be affected by the presence of variants 17671280; 18370842; 19924111 GRIN1 4584 2902 Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive AD/AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21376300; 27164704; 28051072 GRIN2A 4585 2903 Epilepsy, focal, with speech disorder and with or without mental retardation AD Pediatric Neurologic Neurologic Individuals may manifest with seizures, and specific knowledge of the underlying cause can help direct selection of optimal therapies for management based on the genetic etiology 20890276; 23933818; 23933819; 23933820; 24504326; 28212175; 28331464; 30870728 GRIN2B 4586 2904 Mental retardation, autosomal dominant 6, with or without seizures; Developmental and epileptic encephalopathy 27 AD N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20890276; 22521361; 22495309; 23934111; 24272827 GRIN2D 4588 2906 Developmental and epileptic encephalopathy 46 AD Pediatric Neurologic Neurologic The condition involves severe epileptic encephalopathy, and medical management (with NMDA receptor channel blockers) has been reported as effective as adjuvant epilepsy therapy 27616483 GRIP1 18708 23426 Fraser syndrome 3 AR N/A N/A Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22510445; 30280376 GRK1 10013 6011 Oguchi disease 2 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14281981; 9020843; 17070587; 17765441; 19753316; 22959359 GRM1 4593 2911 Spinocerebellar ataxia 44; Spinocerebellar ataxia, autosomal recessive 13 AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22901947; 28886343 GRM6 4598 2916 Night blindness, congenital stationary, type 1B AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11874764; 15781871; 16249515; 16622103; 22008250 GRM7 4599 2917 Neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities AR Pediatric Craniofacial; Endocrine; Neurologic General Among other findings, individuals have been described with endocrine abnormalities, including panhypopituitarism, hypothyroidism, and growth hormone deficiency, and awareness may allow early diagnosis and management of these sequelae 27435318; 28097321; 32286009 GRN 4601 2896 Frontotemporal lobar degeneration with TDP43 inclusions, GRN-related; Neuronal ceroid lipofuscinosis 11 AD/AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6497355; 9633693; 16862116; 16862115; 16983677; 16401619; 16983685; 16495329; 17436289; 17210807; 18392865; 18543312; 18183624; 18413474; 18703462; 18723524; 19884572; 20142524; 20142525; 22338605; 22366770; 22491866; 22608501; 22647257; 22815225; 22890101; 22906081; 22986778 GRXCR1 31673 389207 Deafness, autosomal recessive 25 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 20137778 GRXCR2 33862 643226 Deafness, autosomal recessive 101 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 24619944 GSC 4612 145258 Short Stature, Auditory-Canal Atresia, Mandibular Hypoplasia, and Skeletal Abnormalities (SAMS) AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Genitourinary; Musculoskeletal Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 9475592; 24290375 GSDME 2810 1687 Deafness, autosomal dominant 5 AD N/A N/A Audiologic/Otolaryngologic General The onset of deafness has been described as postlingual Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5919633; 5919636; 9771715; 12126021; 12408063; 14559215; 14676472; 17868390; 17427029; 17868390; 19911014; 21805831 GSN 4620 2934 Amyloidosis, Finnish type AD Adult Cardiovascular; Dermatologic; Neurologic; Ophthalmologic; Renal Cardiovascular Recessive disease has been reported as resulting in a more severe phenotype Individuals with cardiac conduction disease have been described, and surveillance (eg, with electocardiogram) may allow early management (eg, with pacemaker) 4543600; 2153578; 2176164; 1322359; 1311149; 1315718; 8395367; 8684801; 11754099; 16258946; 22068858; 22622774 GSR 4623 2936 Hemolytic anemia due to glutathione reductase deficiency AR Pediatric Hematologic Hematologic Individuals are susceptible to hemolytic anemia, and awareness may allow early management as well as avoidance of triggers of hemolysis (eg, fava beans) 6017801; 17185460 GSS 4624 2937 Glutathione synthetase deficiency AR Pediatric Biochemical; Hematologic; Neurologic; Ophthalmologic Biochemical;Hematologic; Pharmacogenomic Medical therapy (eg, N-acetylcysteine, vitamin E), may improve outcomes, especially if administered early; Hemolysis-causing drugs should be avoided; Acidosis can be medically corrected 13731008; 5901982; 5486400; 5476481; 481537; 3944259; 2502672; 1770788; 1986110; 7937585; 8896573; 11445798; 15717202; 15990954; 16435214; 17206463; 17479648; 19728142; 21988557 GSTZ1 4643 2954 Maleylacetoacetate isomerase deficiency AR N/A N/A Biochemical General The clinical relevance of the condition is unclear 27876694 GTF2E2 4651 2961 Trichothiodystrophy 6, nonphotosensitive AR N/A N/A Dermatologic; Hematologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26996949 GTF2H5 21157 404672 Trichothiodystrophy 3, photosensitive AR N/A N/A Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2189905; 8783572; 15220921; 18470933; 18603627 GTPBP2 4670 54676 Jaberi-Elahi syndrome AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26675814; 29449720 GTPBP3 14880 84705 Combined oxidative phosphorylation deficiency 23 AR Pediatric Biochemical; Cardiovascular Cardiovascular Among other multi-systemic manifestations, the condition may include cardiac manifestations such as hypertrophic cardiomyopathy, and surveillance may allow early diagnosis and management 25434004 GUCA1A 4678 2978 Cone dystrophy 3 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9425234; 15735604; 15953638; 15790869; 19459154; 24024198; 28125083 GUCA1B 4679 2979 Retinitis pigmentosa 48 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15452722 GUCY1A1 4685 2982 Moyamoya disease 6 with or without achalasia AR Pediatric Cardiovascular; Gastrointestinal Cardiovascular Surveillance for cardiovascular complications, as well as related preventive measures to help control contributory factors and clinical manifestations (eg, hypertension) may reduce morbidity and mortality 24581742 GUCY2C 4688 2984 Diarrhea 6; Meconium ileus AD/AR Pediatric Gastrointestinal; Renal Gastrointestinal; Renal Individuals with Meconium ileus have been described with features of Diarrhea 6 (in terms of chronic diarrhea in infancy) In Diarrhea 6, individuals may present in infancy with relatively severe dehydration, metabolic acidosis, and electrolyte disturbances, and preventive measures and early treatment may be beneficial; Awareness of sequelae that may require surgical interventions (eg, small bowel obstruction) may allow prompt recognition and treatment; Individuals may be at increased risk of urolithiasis, and preventive measures and prompt treatment may be beneficial; In Meconium ileus, individuals may present in infancy with relatively severe dehydration, metabolic acidosis, and electrolyte disturbances, and preventive measures and early treatment may be beneficial 4006357; 22436048; 22436048; 22521417 GUCY2D 4689 3000 Choroidal dystrophy, central areolar 1; Cone-rod dystrophy 6; Leber congenital amaurosis, type 1; Cone-Rod dystrophy, autosomal recessive AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8554074; 9097965; 9618177; 11709018; 12015276; 12325031; 12623820; 12552567; 15024725; 20006823; 20301475; 20517349; 22194653; 22695961 GUF1 25799 60558 Developmental and epileptic encephalopathy 40 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26486472 GUSB 4696 2990 Mucopolysaccharidosis type VII AR Pediatric Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic Biochemical The condition can include cardiac manifestations Enzyme replacement therapy is available, and has been approved for both pediatric and adult patients; BMT has been described 4265197; 144057; 101485; 6813001; 1702266; 7680524; 9099834; 9543069; 12403825; 12522561; 12748853; 19224584; 26908836; 28595941; 29478819 GYG1 4699 2992 Glycogen storage disease XV AR Pediatric Allelic with Polyglucosan body myopathy 2 (AR) Biochemical; Cardiovascular; Musculoskeletal Cardiovascular Surveillance to allow early diagnosis and treatment of cardiac complications (eg, treatment of heart failure and arrhythmias via medical management and ICD placement) may be beneficial 20357282; 25272951 GYPA 4702 2993 Blood group, MN locus; Blood group, Erik BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 275842; 7040988; 7052193; 8245024 GYPB 4703 2994 Blood group, Ss BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 3818169; 3456608; 2823938; 3477806 GYPC 4704 2995 Blood group, Gerbich; Blood group, Webb; Blood group, Duch BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 5011657; 7095818; 3539763; 1991173; 1719701; 1413665; 8157284; 11719395; 12469115 GYS1 4706 2997 Glycogen storage disease, type 0, muscle AR Pediatric Biochemical; Cardiovascular; Musculoskeletal; Neurologic Cardiovascular An individual with seizures has been described, but it is not clear if this finding was primarily related to the underlying condition Individuals may manifest with findings such as hypertrophic cardiomyopathy and sudden cardiac arrest and death, and treatment with cardioprotective medications (eg, beta-blockers) has been reported as beneficial 17928598; 21958591 GYS2 4707 2998 Glycogen storage disease, type 0, liver AR Pediatric Biochemical; Gastrointestinal; Neurologic Biochemical Dietary management (eg, with frequent and overnight feeds) can be beneficial 21032403; 4505568; 8831078; 9691087; 11483824; 12794686; 18341095; 20051115; 23426827 GZF1 15808 64412 Joint laxity, short stature, and myopia (JLSM) AR N/A N/A Audiologic/Otolaryngologic; Musculoskeletal; Ophthalmologic General Individuals are at risk for ophthalmologic features such as retinal detachment Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28475863 H1-4 4718 3008 Rahman syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28475857 H19 4713 283120 Wilms tumor 2; Beckwith-Wiedemann syndrome AD (with imprinting) Pediatric Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Renal Endocrine; Oncologic Inheritance involves imprinting; The condition may include the presence of multiple congenital anomalies Surveillance for and early diagnosis of Wilms tumor could be beneficial in order to allow early treatment, which could benefit related morbidity and mortality; Recognition and surveillance for and treatment of neonatal hypoglycemia can be beneficial 15314640; 15743916; 18836444 H6PD 4795 9563 Cortisone reductase deficiency AR N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10522997; 12858176; 15827106; 18628520 HAAO 4796 23498 Vertebral, cardiac, renal, and limb defects syndrome 1 AR N/A N/A Cardiovascular; Gastrointestinal; Musculoskeletal; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28792876 HABP2 4798 3026 Thyroid cancer, nonmedullary 5 AD Pediatric Oncologic Oncologic Individuals have been described as being susceptible to nonmedullary thyroid cancer, and awareness may allow early surveillance, diagnosis, and management 26222560 HACE1 21033 57531 Spastic paraplegia and psychomotor retardation with or without seizures AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26424145; 26437029 HADH 4799 3033 3-hydroxyacyl-CoA dehydrogenase deficiency; Hyperinsulinemic hypoglycemia, familial, 4 AR Pediatric Biochemical; Endocrine; Gastrointestinal Cardiovascular; Endocrine; Gastrointestinal Individuals may present with hypoglycemic seizures, which can lead to neurologic sequelae, and measures to treat/prevent hypoglycemia (eg, with diazoxide) can be effective; In the longer-term, medical and/or surgical treatment (eg, with pancreatectomy, glucagon) may help prevent severe sequelae; In 3-hydroxyacyl-CoA dehydrogenase deficiency, surveillance for cardiovascular manifestations (eg, cardiomyopathy) may allow prompt management; Liver transplant has been described 4193973; 904979; 1835339; 10347277; 10931422; 11489939; 12400064; 14693719; 15870679; 16725361; 19417036; 19318379; 20301549; 21347589; 23273570 HADHA 4801 3030 Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency; Trifunctional protein deficiency AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic Biochemical Variants are also related to maternal HELLP syndrome and Acute fatty liver of pregnancy Early diagnosis to allow interventions such as avoidance of fasting and urgent metabolic care in the setting of acute metabolic decompensation can reduce morbidity and mortality 7813533; 7811722; 7846063; 8770876; 10518281; 12621125; 17143551; 21549624; 21103935; 21630065 HADHB 4803 3032 Trifunctional protein deficiency AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic Biochemical Variants are also related to maternal HELLP syndrome and Acute fatty liver of pregnancy Early diagnosis to allow interventions such as avoidance of fasting and urgent metabolic care in the setting of acute metabolic decompensation may reduce morbidity and mortality 8163672; 7738175; 8651282; 9259266; 12754706; 19699128; 21549624; 22000755; 21630065; 24664533; 33744096 HAL 4806 3034 Histidinemia AR N/A N/A Biochemical General The clinical relevance of the condition is unclear The clinical relevance of the condition is unclear 13704885; 13863215; 4421298; 6192285; 6410118; 8669938; 15806399; 20156889 HAMP 15598 57817 Hemochromatosis, type 2B AR Pediatric Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic Biochemical; Gastrointestinal; Hematologic Digenic inheritance (with HFE) has been reported; HAMP variants may contribute to severity/manifestations of hemochromatosis associated with variants in other genes Patients may benefit from surveillance related to iron overload, and from interventions such as venesection; Certain agents should be avoided (eg, alcohol consumption; iron-containing compounds; uncooked seafood); Hormone therapy may be beneficial in order to prevent osteoporosis 10205270; 12490283; 12915468; 12469120; 15099344; 15345104; 14670915; 15024747; 15198949; 16204153; 19214511; 20301349; 22297252; 22924847 HARS1 4816 3035 Usher syndrome, type 3B AR Pediatric Allelic with Charcot-Marie-Tooth disease, axonal, type 2W (AD) Audiologic/Otolaryngologic; Neurologic; Ophthalmologic Audiologic/Otolaryngologic Hearing loss data unclear but suggestive of early loss Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 22279524; 22930593; 26072516 HARS2 4817 23438 Perrault syndrome 2 AR Pediatric Audiologic/Otolaryngologic; Endocrine; Genitourinary; Obstetric Audiologic/Otolaryngologic Females have been described as being affected by genitourinary anomalies in addition to hearing impairment Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 517579; 21464306 HAVCR2 18437 84868 T-cell lymphoma, subcutaneous panniculitis-like AR Pediatric Oncologic Oncologic Individuals have been described as being susceptible to form of T-cell non-Hodgkin lymphoma, and awareness may allow early surveillance, diagnosis, and management (immunosuppressive and chemotherapeutic treatment has been reported as effective); HSCT has been reported as curative 30374066; 30792187 HAX1 16915 10456 Neutropenia, severe congenital, 3 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Neurologic; Oncologic Allergy/Immunology/Infectious; Oncologic Individuals manifest with findings including susceptibility to severe bacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Use of G-CSF has been reported, as well as treatment with BMT; Surveillance for malignancies may allow early detection and treatment, as there is an increased risk of manifestations such as acute myeloid leukemia and myelodysplastic syndrome 13326376; 17187068; 18337561; 21108402 HBA1 4823 3039 Heinz body anemias; Erythrocytosis, familial, 7; Alpha-thalassemia (Hemoglobin Bart syndrome); Alpha-thalassemia (Hemoglobin H disease) AD/AR/Digenic Pediatric Allelic with Methemoglobinemia, beta type (AD) Hematologic Hematologic; Pharmacogenomic RBC transfusions may be effective for individuals with HbH disease during hemolytic/aplastic crises; Individuals with HbH disease should be monitored for hemolytic/aplastic crisis during febrile episodes; Monitoring should be performed in order to assess iron overload; For Erythrocytosis, phlebotomy has been described as beneficial in some individuals; Individuals with HbH should avoid inappropriate iron therapy, oxidant drugs (eg sulphonamides), some antimalarials; Variants may also result in a variety of hematologic disease (eg, hemolytic anemia), and genetic diagnosis may aid early recognition and treatment, as well as avoid uneccesary treatments (eg, splenectomy in Heinz body anemia) 980019; 8704193; 6199634; 2649166; 2831458; 4138824; 4311041; 7615401; 8416301; 9405682; 9516118; 10676771; 10215545; 10339580; 11283697; 12393486; 14184033; 15921161; 16138310; 18818920; 19205971; 20301608; 21381239; 22531344; 22631041; 24006930; 24081251; 24136020 HBA2 4824 3040 Heinz body anemias; Erythrocytosis, familial, 7; Alpha-thalassemia (Hemoglobin Bart syndrome); Alpha-thalassemia (Hemoglobin H disease) AD/AR/Digenic Pediatric Hematologic Hematologic; Pharmacogenomic RBC transfusions may be effective for individuals with alpha-thalassemia or HbH disease during hemolytic/aplastic crises; Individuals with HbH disease should be monitored for hemolytic/aplastic crisis during febrile episodes; Monitoring should be performed in order to assess iron overload; For Erythrocytosis, phlebotomy has been described as beneficial in some individuals; Individuals with HbH should avoid inappropriate iron therapy, oxidant drugs (eg sulphonamides), some antimalarials; Variants may also result in a variety of hematologic disease (eg, hemolytic anemia), and genetic diagnosis may aid early recognition and treatment, as well as avoid uneccesary treatments (eg, splenectomy in Heinz body anemia) 8704193; 9516118; 2831458; 4138824; 10676771; 14184033; 15266345; 12393486; 15921161; 16461765; 18818920; 20301608; 22631041 HBB 4827 3043 Beta-thalassemia; Heinz body anemias; Erythrocytosis, familial 6; Sickle cell disease; Thalassemia-beta, dominant inclusion body; Other Thalassemias/Hemoglobinopathies AD/AR/Digenic Pediatric Allelic with Hereditary persistence of fetal hemogoblin (AD); Methemoglobinemia, beta type (AD) Allergy/Immunology/Infectious; Cardiovascular; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Pulmonary Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Pulmonary The LCRB region is also relevant For beta-thalassemia, specific treatments (eg, transfusions, as well as managing related issues such as potential iron overload), can be effective; For Erythrocytosis, phlebotomy has been described as beneficial in some individuals; For sickle cell anemia, surveillance, immune prophylaxis, and preventive measures (eg, hydroxyurea, prophylactic antibiotics) can be effective in reducing morbidity, as well as aid in the prompt recognition and treatment of crises and sequelae; Variants may also result in a variety of hematologic disease (eg, hemolytic anemia), and genetic diagnosis may aid early recognition and treatment (eg, with RBC transfusion), as well as avoid uneccesary treatments (eg, splenectomy in Heinz body anemia) 4232783; 4311041; 4351905; 49057; 7137165; 14184033; 1586746; 3048433; 2563949; 1971109; 1707292; 17795074; 1814856; 7715639; 8201467; 8416301; 8704193; 8982148; 10861320; 12614204; 13897827; 15921161; 19036119; 19486366; 20098328; 20301599; 20305663; 21131035; 20301551; 22622672; 22631042; 22645178; 22740566; 22786487; 22857974; 22892550; 22899478; 22923496; 22972063; 23018751; 23076916; 23108767 HBG1 4831 3047 Hereditary persistence of fetal hemoglobin AD N/A Allelic with Hereditary persistence of fetal hemogoblin (AD) Hematologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2578620; 2423160; 21057501 HBG2 4832 3048 Cyanosis, transient neonatal AD Pediatric Allelic with Hereditary persistence of fetal hemoglobin (AD) Hematologic Hematologic Though a range of severity has been described, some individuals have been reported as requiring supplemental oxygen and/or RBC transfusions 6158500; 6174163; 6205403; 6208955; 2483933; 8811323; 12603090; 21561349; 22935660 HCCS 4837 3052 Linear skin defects with multiple congenital anomalies 1 (MIDAS syndrome) XL Pediatric Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic Audiologic/Otolaryngologic; Cardiovascular Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; As individuals have been described with a variety of cardiovascular anomalies, surveillance (eg, with echocardiogram/electrocardiogram) may allow detection and early management of related manifestations 16059943; 17033964; 17893649; 20301767; 21200317 HCFC1 4839 3054 Combined methylmalonic acidemia and hyperhomocysteinemia XL Pediatric Biochemical; Neurologic Biochemical Medical interventions (eg, cofactor therapy with injectable hydroxycobalamin) and dietary management (eg, high-calorie, low protein diet and avoidance of fasting, with measures taken to avoid/treat decompensation) may be to beneficial in both acute and chronic states 24011988 HCN1 4845 348980 Epileptic encephalopathy, early infantile, 24; Generalized epilepsy with febrile seizures plus, type 10 AD N/A N/A Neurologic General As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24747641; 29936235; 30351409 HCN4 16882 10021 Brugada syndrome 8; Sick sinus syndrome 2 AD Pediatric Cardiovascular Cardiovascular; Pharmacogenomic Variants may result in several cardiac conditions involving arrhythmia, and, depending on the condition, surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever 8750801; 12750403; 15123648; 16407510; 17646576; 19165230; 20301690 HCRT 4847 3060 Narcolepsy 1 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10973318 HDAC4 14063 9759 Brachydacytly-mental retardation syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General An individual with, among other manifestations, cardiovascular anomalies and sensorineural hearing loss, has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20691407; 24715439 HDAC6 14064 10013 Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia XL N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16001442; 20181727 HDAC8 13315 55869 Cornelia de Lange syndrome 5 XL N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1746601; 22885700; 24403048; 25209348; 25644381 HDC 4855 3067 Tourette's syndrome AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20445167 HECW2 29853 57520 Neurodevelopmental disorder with hypotonia, seizures, and absent language AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27334371; 27389779 HELLS 4861 3070 Immunodeficiency-centromeric instability-facial anomalies syndrome 4 AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Neurologic Allergy/Immunology/Infectious Individuals have been described with recurrent childhood infections, and awareness may allow prompt and aggressive treatment of infections 26216346 HEPACAM 26361 220296 Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation; Megalencephalic leukoencephalopathy with subcortical cysts 2A AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20517947; 21419380 HEPHL1 30477 341208 Abnormal hair, joint laxity, and developmental delay AR N/A N/A Biochemical; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31125343 HERC1 4867 8925 Macrocephaly, dysmorphic facies, and psychomotor retardation AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26138117; 26153217; 27108999 HERC2 4868 8924 Skin/hair/eye pigmentation 1; Mental retardation, autosomal recessive 38 AD/AR N/A N/A Dermatologic; Neurologic General Skin/hair/eye pigmentation 1 may not have clinical relevance, but may act a susceptibility factor locus for a multifactorial disease (melanoma); For Nonsyndromic intellectual disability, autism, and gait disturbance, genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17952075; 18172690; 18252221; 18252222; 21471978; 21926416; 22065085; 22234890; 23065719; 23243086 HES7 15977 84667 Spondylocostal dysostosis 4, autosomal recessive AR N/A N/A Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18775957; 20087400; 20301771 HESX1 4877 8820 Pituitary hormone deficiency, combined; Septooptic dysplasia AR/AD Pediatric Endocrine; Neurologic; Ophthalmologic Endocrine Some individuals may have life-threatening adrenal insufficiency as well as additional endocrine insufficiency, and early recognition and immediate and long-term treatment can be beneficial 8696006; 9620767; 11136712; 14561704; 12519827; 16940453; 22145475 HEXA 4878 3073 Tay-Sachs disease; GM2-gangliosidosis; Hexosaminidase A deficiency AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5793973; 175770; 3375249; 2848800; 2140574; 2220809; 2824459; 2137287; 9090523; 15557512; 15714079; 15108204; 15956171; 20301397; 21937992; 21967858; 22441121; 22723944; 22789865 HEXB 4879 3074 Sandhoff disease AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Substrate reduction therapy has been described as potentially beneficial; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5651108; 571983; 3017984; 2948136; 8357844; 15956171; 18758829; 19898952; 20798201; 21150067; 22789865; 22848519; 23046579; 23113155 HFE 4886 3077 Hemochromatosis AR/Digenic Pediatric Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic Biochemical; Gastrointestinal; Hematologic Heterozygotes may display mild manifestations in some circumstances; Digenic inheritance (with HAMP) has been described Interventions such as phlebotomy (including when presymptomatic) and dietary measures may be effective, though there is some controversy regarding specifics 678784; 3979748; 4058506; 3658574; 2919850; 2346731; 1614776; 8419246; 8051482; 8943161; 8696333; 9132598; 9867745; 9867746; 9792863; 9687253; 11336458; 10401000; 10471457; 11069625; 11087882; 10673305; 10673304; 11260010; 11386022; 11423500; 11325323; 11565552; 12915468; 14618419; 15024747; 15347835; 15175440; 15466004; 15657376; 18061062; 18566337; 18809761; 19214511; 20843714; 21901659; 21411349; 22265917; 22196777; 20301613 HFM1 20193 164045 Premature ovarian failure 9 AR Pediatric Endocrine; Obstetric Obstetric Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency 24597873 HGD 4892 3081 Alkaptonuria AR Pediatric Biochemical; Cardiovascular; Musculoskeletal; Renal Biochemical; Cardiovascular; Musculoskeletal; Renal The condition can include cardiac complications, and surveillance for early detection and management of manifestations such as aortic dilatation, valvular disease, or coronary artery calcification may be beneficial; Awareness of complications including urolithiasis and joint degeneration may allow prompt recognition and treatment; Other, more specific therapies are under investigation 12784973; 5472968; 2667832; 2771520; 2270175; 2316305; 8782815; 9154114; 9529363; 9809834; 10482952; 10594001; 11001939; 10970188; 10945668; 12359141; 12501223; 12872815; 15260431; 20301627; 21620748; 21927854; 22482092; 22772574; 23035044; 23357094; 23353776; 23430897; 23430917; 23438536; 23466771; 23486607; 23619548; 23879342; 24009934; 24009959 HGF 4893 3082 Deafness, autosomal recessive 39 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 14512973; 19576567 HGSNAT 26527 138050 Mucopolysaccharidosis type IIIC (Sanfilippo syndrome C); Retinitis pigmentosa 73 AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Gastrointestinal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33384; 3142713; 16960811; 17033958; 18024218; 18518886; 19479962; 20583299; 20825431; 25859010 HHAT 18270 55733 Nivelon-Nivelon-Mabille syndrome AR N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1342874; 24784881; 30912300 HIBCH 4908 26275 3-hydroxyisobutryl-CoA hydrolase deficiency AR Pediatric Biochemical;Neurologic Biochemical Dietary measures (eg, low-protein, high carbohydrate) especially in ketosis, as well as medical treatment (eg, carnitine) may be beneficial) 7122152; 17160907; 24299452; 26026795; 26163321 HIKESHI 26938 51501 Leukodystrophy, hypomyelinating, 13 AR N/A N/A Cardiovascular; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26545878 HINT1 4912 3094 Neuromyotonia and axonal neuropathy, autosomal recessive AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22961002 HIVEP2 4921 3097 Mental retardation, autosomal dominant 43 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23020937; 26153216; 27003583 HJV 4887 148738 Hemochromatosis, type 2A AR Pediatric Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic Biochemical; Gastrointestinal; Hematologic Variants may also modify the severity of HFE-related hemochromatosis Patients may benefit from surveillance related to iron overload, and from interventions such as venesection; Certain agents should be avoided (eg, alcohol consumption; iron-containing compounds; uncooked seafood); Hormone therapy may be beneficial in order to prevent osteoporosis 10205270; 12891378; 14982873; 15254010; 14982867; 14647275; 15461631; 15811010; 17847004; 18492090; 19796184; 20301349 HK1 4922 3098 Hemolytic anemia, nonspherocytic, due to hexokinase deficiency AR Pediatric Allelic with Retinitis pigmentosa 79 (AD); Neurodevelopmental disorder with visual defects and brain anomalies (AD); Neuropathy, motor and sensory, Russe type (Charcot-Marie-Tooth disease type 4G) (AR) Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Hematologic Individuals may manifest with severe hemolysis, and anemia may be sufficiently severe to require splenectomy 6015552; 27532; 7234862; 6848140; 7655856; 12393545; 19536174; 19608687; 22978647; 25190649; 25316723; 30778173 HLA-A 4931 3105 Drug-induced toxicity, susceptibility to AD Pediatric General Pharmacogenomic Susceptibility to adverse reactions (including Stevens-Johnson syndrome), may have pharmacogenomic relevance related to a number of medications, including allopurinol, carbamazepine; HIV disease, progression in 15743917; 17258541; 21149285; 21428768; 21428769 HLA-B 4932 3106 Drug-induced toxicity, susceptibility to AD Pediatric General Pharmacogenomic Susceptibility to adverse reactions (including Stevens-Johnson syndrome), may have pharmacogenomic importance related to a number of medications, including abacavir, allopurinol, carbamazepine, flucocloxacillin 3477129; 16415921; 16538176; 17258541; 19933789; 203459391; 21244392; 21428768; 21676164; 22348415; 22348435 HLCS 4976 3141 Holocarboxylase synthetase deficiency AR Pediatric Biochemical; Dermatologic; Neurologic; Ophthalmologic Biochemical Biotin therapy can be beneficial to treat severe manifestations (which can include findings such as alopecia, keratoconjunctivitis, lactic acidosis, perioral erosions, and seizures), though the degree of response varies 6798072; 6794361; 6114319; 6790844; 6133032; 8319716; 7842009; 8817339; 9128289; 10190325; 11735028; 12124727; 12855220; 16134170; 16231399; 20095979; 21874615 HMBS 4982 3145 Hydroxymethylbilane synthase deficiency; Porphyria, acute intermittent AD/AR Pediatric Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Oncologic Biochemical; Endocrine; Gastrointestinal; Pharmacogenomic; Oncologic Homozygosity/compound heterozygosity results in a distinct and much more severe phenotype Attacks may be precipitated by porphyrinogenic agents (eg, barbiturates, sulfonamides), which, along with other exacerbating factors (eg, alcohol, infection) should be avoided; Endocrinological interventions may be beneficial in affected females; Acute attacks can be managed with supportive care (including TPN if necessary), and with medical treatment (eg, hematin); Surveillance for complications (eg, hepatocellular carcinoma) is indicated; Liver transplant has been reported as effective 13354248; 14198005; 4907358; 1106284; 329053; 665312; 87561; 449661; 7251856; 7258864; 6878621; 6433194; 2864531; 3724815; 3595653; 2789372; 2563167; 2246851; 2246852; 1577472; 7866402; 9199558; 10343207; 9860299; 10453740; 11071386; 14970743; 15001330; 15534187; 16211556; 17298217; 18627369; 18647325; 19460837; 19656452; 20301372; 22748422 HMCN1 19194 83872 Macular degeneration, age-related, 1 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16020313; 17216616; 25986072 HMGA2 5009 8091 Silver-Russell syndrome 5 AD Pediatric Craniofacial; Endocrine; Musculoskeletal Endocrine Among other findings, response to growth hormone therapy has been described, and awareness may allow early diagnosis and management of this issue 28567303; 28796236; 29501611; 29655892 HMGB3 5004 3149 Microphthalmia, syndromic 13 XL N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4998085; 24993872 HMGCL 5005 3155 3-hydroxy-3-methylglutaryl-CoA lyase deficiency AR Pediatric Biochemical; Neurologic Biochemical Treatment to prevent and efficiently treat metabolic decompenstation can be beneficial; Avoidance of prolonged fasting and chronic low-fat, protein (including leucine)-restricted diet with carnitine supplementation can be beneficial 1256504; 1000856; 91680; 85928; 6156427; 6112838; 6489380; 6475954; 3099065; 3128690; 2246860; 8440722; 8617516; 11129331; 17692550; 19177531; 19932602 HMGCR 5006 3156 Statins, efficacy of AD Pediatric General Pharmacogenomic Selection and dosage of cholesterol-lowering medications may be impacted by genotyping results 15199031; 15367547; 24001602 HMGCS2 5008 3158 3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency AR Pediatric Biochemical; Neurologic Biochemical Specific dietary measures (especially avoidance of fasting) as well as other treatments may be beneficial, both in well and decompensated state 9337379; 9727719; 11228257; 11479731; 16601895 HMOX1 5013 3162 Heme oxygenase 1 deficiency AR N/A N/A Allergy/Immunology/Infectious; Craniofacial; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Renal Allergy/Immunology/Infectious; Hematologic Although the disease may ultimately be fatal, the condition includes immunodeficiency (includind due to asplenia), and prophylaxis and prompt and aggressive treatment of infections may be beneficial; RBC transfusions may be indicated for anemia 9884342; 21088618; 22023467 HMX1 5017 3166 Oculoauricular syndrome AD N/A N/A Craniofacial; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18423520; 21417677; 25574057 HNF1A 11621 6927 Renal cell carcinoma, nonpapillary clear cell; Liver adenomatosis; Maturity onset diabetes of the young, type III AD Pediatric Variants may also cause or be associated with Diabetes mellitus, as in Diabetes mellitus, insulin-dependent, 20 (AD) Endocrine; Oncologic Endocrine; Oncologic Surveillance and early detection of and treatment for neoplasms (eg, including renal and/or hepatic neoplasms) may decrease morbidity and mortality; Individuals with MODY-3 have been reported as presenting in childhood with macrosomia and hyperinsulinism, which has been reported as diazoxide-responsive 8945470; 9313763; 10482964; 11058894; 10649494; 11575290; 11668618; 11904371; 12050210; 12355088; 12355088; 14598263; 15001650; 15649945; 21120312; 21683639; 22517943; 22802087 HNF1B 11630 6928 Renal cell carcinoma, nonpapillary chromophobe AD Adult Allelic with Renal cysts and diabetes syndrome (AD) Endocrine; Genitourinary; Oncologic; Renal Oncologic Surveillance and early detection of and treatment for malignancy may decrease morbidity and mortality 7151342; 2624270; 9398836; 10484768; 11085914; 12161522; 12675839; 15068978; 16249435; 15649945; 21380624; 21617276; 21767339; 22587559; 22269832; 22432796; 22706971 HNF4A 5024 3172 Congenital hyperinsulinism, diazoxide-responsive; Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young; Maturity onset diabetes of the young, 1 AD Pediatric Variants may also cause or be associated with Diabetes mellitus, insulin dependent (AD) Endocrine; Renal Endocrine; Renal Individuals can present in childhood with macrosomia and hyperinsulinism, which has been reported as diazoxide-responsive; For individuals whose phenotype includes Fanconi syndrome, awareness may allow prompt treatment through replacement of lost solutes 8945471; 9313765; 9294105; 9449683; 9920109; 11232004; 12050210; 17407387; 21683639; 21922456; 22802087; 24285859 HNMT 5028 3176 Mental retardation, autosomal recessive 51 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26206890 HNRNPA1 5031 3178 Amyotrophic lateral sclerosis 20; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 AD N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20116073; 23455423 HNRNPA2B1 5033 3181 Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 AD N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23455423 HNRNPDL 5037 9987 Muscular dystrophy, limb-girdle, autosomal dominant 3 AD N/A N/A Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24647604 HNRNPH2 5042 3188 Mental retardation, X-linked, syndromic, Bain type XL N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27545675 HNRNPK 5044 3190 Au-Kline syndrome AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26173930 HNRNPU 5048 3192 Developmental and epileptic encephalopathy 54 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23708187; 23934111; 25356899; 27652284 HOGA1 25155 112817 Hyperoxaluria, primary, type III AD/AR Pediatric Biochemical; Renal Renal Increased fluid intake in order to promote hydration as well as medical therapy (eg, neutral phosphate therapy, citrate medications, thiazides) may be beneficial 20797690; 21896830; 22781098; 22688746; 22391140 HOMER2 17513 9455 Deafness, autosomal dominant 68 AD N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25816005 HOXA1 5099 3198 Athabaskan brainstem dysgenesis syndrome; Bosley-Salih-Alorainy syndrome AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Neurologic Audiologic/Otolaryngologic The conditions can involve multiple congenital anomalies Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 16155570; 18412118; 20075099 HOXA11 5101 3207 Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 AD Pediatric Hematologic; Musculoskeletal Hematologic Individuals can have symptomatic thrombocytopenia and bone marrow failure manifesting in the neonatal period, requiring early bone marrow/umbilical cord stem cell transplantation 11101832; 11442476; 16765069; 20562651 HOXA13 5102 3209 Hand-foot-genital syndrome; Guttmacher syndrome; Hand-foot-uterus syndrome AD N/A N/A Genitourinary; Musculoskeletal; Renal Renal The disorder may be recognizable in the majority of individuals, but individuals are at risk of renal findings such as unrecognized vesicoureteral reflux, which can cause renal damage, and prophylactic/treatment measures can be beneficial 5450271; 8484413; 9020844; 10839976; 11968094; 12073020; 12414828; 12676922; 19591980; 20301596; 21549968 HOXA2 5103 3199 Microtia, hearing impairment, and cleft palate AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 18394579 HOXB1 5111 3211 Facial paresis, hereditary congenital, 3 AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 22770981 HOXC13 5125 3229 Ectodermal dysplasia 9 AR N/A N/A Dermatologic General Males have been described as being affected with genitourinary anomalies, some of which require interventions; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23063621 HOXD10 5133 3236 Vertical talus, congenital AD N/A N/A Musculoskeletal General One described family was also affected by Charcot-Marie-Tooth disease Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15146389; 16450407 HOXD13 5136 3239 Brachydactyly-syndactyly syndrome; Brachydactyly, type D; Brachydactyly, type E1; Syndactyly, type V; Synopolydactyly, type I, Synopolydactyly, type II; Synopolydactyly with clefting, autosomal recessive AD/AR N/A N/A Craniofacial; Musculoskeletal Renal The condition has also been implicated in VACTERL association (AD), but the pathogenesis is unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7666393; 8817328; 8614804; 8933344; 9758628; 11778160; 12116248; 12649808; 12900906; 16222680; 17236141; 19006232; 18177473; 19060004; 20974300; 21814222; 22233338; 22373878; 22374128; 22406499; 22473151 HP 5141 3240 Anhaptoglobinemia; Hypohaptoglobinemia AR Pediatric Hematologic Hematologic Variants may be important in specific situations (eg, related to transfusion) 9463309; 10666182; 14999562 HPCA 5144 3208 Dystonia 2, torsion, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14694054; 25799108 HPD 5147 3242 Hawksinuria; Tyrosinemia, type III AD/AR Pediatric Biochemical; Neurologic Biochemical It is unclear if a strict low tyrosine diet alters the natural history of tyrosinemia type III, though some have suggested that treatment may be important, especially in infancy In Tyrosinemia III, specific dietary measures (eg, restriction of phenylalanine and tyrosine) are recommended; In Hawksinuria, individuals may present with manifestations including failure to thrive, and a protein-restricted diet has been reported as beneficial in some instances 1130176; 858207; 7278885; 6828337; 6132360; 1519651; 9343288; 10412819; 10942115; 11073718; 11916315; 17560158 HPDL 28242 84842 Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities; Spastic paraplegia 83, autosomal recessive AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32707086 HPGD 5154 3248 Hypertrophic osteoarthropathy, primary, autosomal recessive 1; Digital clubbing, isolated congenital AR Pediatric Allelic with Digital clubbing, isolated congenital (AR) Musculoskeletal General Medical treatment (eg, with sulfasalazine, methotrexate) has been described as beneficial related to joint manifestations 9402870; 17551338; 17285282; 18500342; 18805827; 19306095; 19568269; 20299379; 20406614; 21426412; 24533558 HPRT1 5157 3251 Hyperuricemia, HPRT related (Kelley-Seegmiller syndrome); Lesch-Nyhan syndrome XL Pediatric Biochemical; Hematologic; Musculoskeletal; Neurologic; Renal Biochemical; Renal In Lesch-Nyhan syndrome, an allelic condition, as in Kelley-Seegmiller syndrome, control of uric acid production can be effective to reduce sequelae, but does not affect Neurological manifestations Treatments related to uric acid overproduction, such as alkalinization and allopurinol, can be effective in order to prevent and treat sequelae such as renal dysfunction and gouty arthritis 14142409; 4291947; 4322125; 3600927; 10657589; 11891689; 20301328; 20558399; 31182398 HPS1 5163 3257 Hermansky-Pudlak syndrome 1 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pulmonary Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pharmacogenomic; Pulmonary Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS; Lung transplantation has been described 3921802; 2916560; 8896559; 9562579; 9497254; 10411151; 10768343; 11414528; 12126938; 16210149; 19398212; 19729668; 20301464; 20514622; 20662851; 21833017 HPS3 15597 84343 Hermansky-Pudlak syndrome 3 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pulmonary Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS 11455388; 20301464 HPS4 15844 89781 Hermansky-Pudlak syndrome 4 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pulmonary Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pharmacogenomic; Pulmonary Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS 11836498; 20301464; 21833017 HPS5 17022 11234 Hermansky-Pudlak syndrome 5 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pulmonary Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS 12548288; 20301464; 21833017 HPS6 18817 79803 Hermansky-Pudlak syndrome 6 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic; Pulmonary Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Prompt treatment of pulmonary infections (as well as avoidance of cigarette smoke) to maximize pulmonary function is indicated, including influenza and pneumococcus vaccination; Surveillance related to ophthalmologic, gastrointestinal, and other manifestations has been recommended in all individuals with HPS 12548288; 20301464; 27225848 HPSE2 18374 60495 Ochoa syndrome; Urofacial syndrome 1 AR Pediatric Craniofacial; Neurologic; Renal Renal Individuals are at high risk of infantile-onset vesicoureteral reflux leading to kidney damage, hypertension, and eventual renal failure, and surveillance and preventive measures related to manifestations such as urinary tract/renal infections may be beneficial 11446407; 19839856; 19669792; 20560209; 20560210; 20605127; 21332471; 21450525 HR 5172 55806 Atrichia with papular lesions; Alopecia universalis congenita AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13150805; 13763141; 5570254; 9758627; 10205263; 10827399; 11410842; 12271294; 11982770; 12880440; 17869066; 10417283; 11069461; 10854110; 10777357; 15149494; 17680008; 21272494; 21919222; 22584530 HRAS 5173 3265 Costello syndrome AD Pediatric Cardiovascular; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Oncologic Cardiovascular; Oncologic The condition may be frequently clinically recognizable, but often includes cardiovascular manifestations, including structural anomalies, hypertrophic cardiomyopathy, and arrhythmias, as well as an elevated risk for malignancy, and surveillance and appropriate care may be beneficial 907573; 8882404; 8834040; 9863604; 9521961; 10424828; 10449656; 10678668; 11857557; 11857556; 12210337; 12561057; 12605434; 16170316; 15940703; 16372351; 16329078; 16969868; 16443854; 17551924; 17412879; 17054105; 18042262; 18247425; 18302240; 19213030; 19288554; 19206176; 20301680; 20425820; 21438134; 21495179; 21834037; 22098123; 22261753; 22420426; 22488832; 22495831; 22495892; 22510203; 22887473; 22926243; 23429430; 23751039; 23813656; 23918324; 24057668 HRG 5181 3273 Thrombophilia due to histidine-rich glycoprotein deficiency AD Adult Hematologic Hematologic Elevated histidine-rich glycoprotein (HRG) has also been described as associated with risk of thromboembolism Individuals are at risk for thromboembolic events.and related sequelae, and knowledge may allow preventive measures as well as prompt treatment of manifestations 3689697; 8236132; 7769366; 8815595; 11057869 HRURF 55085 120766137 Hypotrichosis 4 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19122663; 20659777; 20814945 HS2ST1 5193 9653 Neurofacioskeletal syndrome with or without renal agenesis AR N/A N/A Craniofacial; Musculoskeletal; Ophthalmologic; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33159882 HS6ST1 5201 9394 Hypogonadotropic hypogonadism 15, with or without anosmia AD/AR/Digenic/Multigenic Pediatric Endocrine; Musculoskeletal; Neurologic Endocrine Relatively complex models of inheritance such as digenic inheritance and interaction with other related loci (eg, FGF8-network-associated genes) have been described Surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to male fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 21700882; 23643382 HS6ST2 19133 90161 Mental retardation, X-linked, syndromic, Paganini-Miozzo type XL N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30471091 HSD11B1 5208 3290 Cortisone reductase deficiency 2 AD/AR (Triallelic) AD N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3990293; 8923828; 10522997; 12858176; 21325058 HSD11B2 5209 3291 Cortisol 11-beta-ketoreductase deficiency AR Pediatric Endocrine; Renal Renal There is a broad range of severity, including potentially lethal early chidlhood disease, and medical treatment (eg, with spironolactone) can be beneficial 870517; 1740492; 3460996; 3164727; 8370690; 7670488; 9683587; 9707624; 10536001; 10523339; 17314322; 19909806 HSD17B10 4800 3028 HSD10 mitochondrial disease XL N/A N/A Audiologic/Otolaryngologic; Biochemical; Neurologic General Dietary measures (eg, isoleucine restriction) and medications (eg, benzhexol, mitochondrial cocktails), have been reported, but the overall efficacy has been decribed as ineffective Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10521307; 11102558; 12112118; 12555940; 12696021; 12872843; 14729408; 15059617; 16148061; 17236142; 19706438; 20664630; 22132097; 22127393 HSD17B3 5212 3293 17-Beta hydroxysteroid dehydrogenase III deficiency AR Pediatric Endocrine; Genitourinary Endocrine; Genitourinary Prepubertal diagnosis may allow surgical treatment via removal of abnormal testes, preventing typical presenting clinical signs in puberty (marked masculinization and hirsutism) 2998649; 8075637; 8550739; 10599740; 21700882; 22212252; 22594312; 22445608; 22876557 HSD17B4 5213 3295 Perrault syndrome 1 AR Pediatric Allelic with D-bifunctional protein deficiency (AR) Audiologic/Otolaryngologic; Biochemical; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Obstetric Audiologic/Otolaryngologic The condition may be clinically recognizable in females, and the exact onset of hearing loss is unclear, but evidence suggests a prelingual onset Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 4061497; 2868085; 2882519; 2921319; 2122104; 1357231; 8147505; 8279468; 9482850; 9915948; 10400999; 11992265; 11743515; 15216544; 16385454; 20673864; 23181892; 24553428 HSD3B2 5218 3284 Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency AR Pediatric Endocrine; Genitourinary Endocrine Adrenal replacement can be effective, though individuals may nevertheless demonstrate severe manifestations 13968789; 295036; 3088022; 2826919; 1309452; 1363812; 14764797; 18252794; 24553428 HSD3B7 18324 80270 Bile acid synthesis defect, congenital, 1 AR Pediatric Gastrointestinal Gastrointestinal Due to early-onset progressive hepatic disease, affected invididuals commonly present in infancy with failure to thrive and coagulopathy, and typically demonstrate a favorable response to medical treatment (with oral bile acid therapy) 3470305; 11067870; 12679481; 22095780 HSF2BP 5226 11077 Premature ovarian failure 19 AR Pediatric Obstetric Obstetric The condition can involve infertility, and fertility treatment has been described as successful in some indviduals 32845237 HSF4 5227 3299 Cataract 5, multiple types AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3233780; 12089525; 18941546; 19014451; 20670914 HSPA1L 5234 3305 Abacavir, susceptibility to toxicity with AD Pediatric General Pharmacogenomic Medication choice and administration may be affeted by the presence of variants 11943262; 11888582; 15024131 HSPA9 5244 3313 Anemia, sideroblastic 4 AD Pediatric Allelic with Even-Plus syndrome (AR) Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal Hematologic Even-Plus syndrome can involve multiple congenital anomalies Individuals have been described with anemia requiring RBC transfusions in some individuals, and awareness may allow for surveillance and prompt management 3653362; 26491070; 26598328 HSPB1 5246 3315 Neuropathy, distal hereditary motor, type IIB; Charcot-Marie-Tooth disease, axonal, type 2F AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11528513; 15122254; 16087758; 18325928; 18832141; 18952241; 20301462; 20870250; 22176143 HSPB3 5248 8988 Neuronopathy, distal hereditary motor, type IIC AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20142617 HSPB8 30171 26353 Charcot-Marie-Tooth disease, axonal, type 2L; Neuronopahty, distal hereditary motor, type IIA AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1517763; 15122253; 15021985; 15565283; 18325928; 20538880; 21985219 HSPD1 5261 3329 Spastic paraplegia 13, autosomal dominant; Leukodystrophy, hypomyelinating, 4 AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10677329; 11898127; 17420924; 18571143 HSPG2 5273 3339 Schwartz-Jampel syndrome, type 1 AD/AR Pediatric Allelic with Dyssegmental dysplasia, Silverman-Handmaker type (AR) Craniofacial; Musculoskeletal General; Pharmacogenomic An increased risk of malignant hyperthermia has been described; Variants may have additional pharmacogenomic importance (eg, related to tardive dyskinesia); Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13909723; 4953364; 11101850; 11038441; 11279527; 11941538; 16927315; 20072119; 20542149; 21808285 HTR1A 5286 3350 Periodic fever, menstrual cycle dependent AD Pediatric Allergy/Immunology/Infectious; Endocrine; Obstetric Allergy/Immunology/Infectious As the disorder affects females, the onset may be in the pediatric timeframe due to the typical age of menarche, though reported individuals have been typically described as older Fevers have been reported as responding to medical treatments such as HTR1A-agonists 21990073 HTR2A 5293 3356 Major depressive disorder, response to citalopram therapy in; Clozapine, response to AD Pediatric General Pharmacogenomic Variants may relate to the efficacy of medications such as Citalopram and clozapine 9491814; 12563180; 16642436 HTRA1 9476 5654 Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy type 2 (CADASIL2); Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) AD/AR N/A N/A Cardiovascular; Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17053108; 17053109; 17884985; 17568988; 18511946; 19387015; 20437615; 21115960; 21482952; 22900900; 24500651; 26063658 HTRA2 14348 27429 3-methylglutaconic aciduria type VIII AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27208207; 27696117 HTT 4851 3064 Huntington disease; Lopes-Maciel-Rodan syndrome (LOMARS) AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2992086; 2881213; 8401589; 8401587; 8458085; 8401588; 7826277; 8659522; 9150168; 11553930; 12791042; 16096998; 17240289; 19776381; 19455596; 26740508; 27329733 HUWE1 30892 10075 Mental retardation, X-linked syndromic, Turner type; Xp11.22 microduplication syndrome XL N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General In Xp11.22 microduplication syndrome, the phenotype appears to be due to increased HUWE1 dosage 25985138; 27130160; 27615324; 27884935; 29180823; 30797980 HYAL1 5320 3373 Mucopolysaccharidosis type IX AR N/A N/A Biochemical; Craniofacial; Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8793927; 10339581 HYDIN 19368 54768 Ciliary dyskinesia, primary, 5 AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Pulmonary Pulmonary surveillance may be beneficial to assess respiratory function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 14985390; 23022101; 23849777 HYLS1 26558 219844 Hydrolethalus syndrome AR N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Pulmonary General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7028327; 15843405; 18648327 HYOU1 16931 10525 Immunodeficiency 59 and hypoglycemia AR Pediatric Allergy/Immunology/Infectious; Endocrine Allergy/Immunology/Infectious; Endocrine The condition has been described as involving recurrent infection, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Abnormal gluocose metabolism (resulting in hypoglycemia) has been described, and awareness may allow prompt management 27913302 IARS1 5330 3376 Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy AR Pediatric Biochemical; Gastrointestinal; Musculoskeletal; Neurologic Biochemical Patients have been shown to have zinc deficiency (possibly related to chronic liver disease), and medical management (with zinc supplementation) has been shown to be beneficial 27426735 IARS2 29685 55699 Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia (CAGSSS) AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Endocrine; Musculoskeletal; Ophthalmologic; Neurologic Audiologic/Otolaryngologic; Endocrine Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Awareness of growth hormone deficiency may allow early recognition and treatment 8409271; 25130867 IBA57 27302 200205 Multiple mitochondrial dysfunctions syndrome 3; Spastic paraplegia 74, autosomal recessive AR N/A N/A Biochemical; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23462291; 25609768 ICAM4 5347 3386 Blood group, Landsteiner-Wiener BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 7632968; 8639917 ICOS 5351 29851 Immunodeficiency, common variable, 1 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis (including with administration of IVIG) and early and aggressive treatment of infections may be beneficial 12577056; 15507387; 18424338; 19426217; 20301476; 21970952 IDH2 5383 3418 D-2-hydroxyglutaric aciduria 2 AD N/A N/A Biochemical; Cardiovascular; Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20847235 IDH3A 5384 3419 Retinitis pigmentosa 90 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28412069; 30058936; 31012789 IDH3B 5385 3420 Retinitis pigmentosa 46 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18806796 IDS 5389 3423 Mucopolysaccharidosis type II XL Pediatric Biochemical; Cardiovascular Biochemical Enzyme replacement therapy is available and may positively influence biochemical parameters and some outcomes (such as height and endurance), but there is not evidence that the outcome would be positively affected with earlier (genetic) diagnosis, and replacement may not affect neurologic (CNS) manifestations; Awareness of multisystemic involvement, including cardiac manifestations, may allow early and beneficial management of sequelae such as cardiac valvular disease; BMT has been reported 4622960; 1901826; 1906048; 1303211; 8111411; 7581397; 8940265; 9660053; 9762601; 9501270; 9921913; 10399096; 16912578; 17185020; 18038146; 19901005; 19748810; 20301451; 21502868; 23497636; 23537841; 25541100; 28595941 IDUA 5391 3425 Mucopolysaccharidosis type I AR Pediatric Biochemical; Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary Biochemical The condition includes a wide degree of severity, and multiple subtypes, including Scheie syndrome, Hurler-Scheie syndrome, and Hurler syndrome Enzyme replacement therapy, the timing of which affects outcome is available, but may not affect cerebral manifestations; HSCT and umbilical cord blood transplantation has been described as beneficial 6139633; 9516162; 7550242; 11735025; 11172140; 15128896; 19748810; 20301341; 21502868; 25103575; 28595941 IER3IP1 18550 51124 Microcephaly, epilepsy, and diabetes syndrome 1 AR Pediatric Endocrine; Neurologic Endocrine Individuals may have early-onset diabetes, which may be difficult to control Among other findings, individuals may have early-onset diabetes, which may be difficult to control, and awareness may allow early diagnosis and medical management 16972080; 21835305; 24138066 IFIH1 18873 64135 Aicardi-Goutieres syndrome 7; Singleton-Merten syndrome 1 AD Pediatric Allergy/Immunology/Infectious; Cardiovascular; Dental; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary Cardiovascular; Ophthalmologic; Pulmonary Individuals with Aicardi-Goutieres syndrome may have pulmonary hypertension, and awareness may allow surveillance, prompt diagnosis of disease, and management of this sequelae; Among other manifestations, Singleton-Merton syndrome 1 can include cardiovascular calcifications, and awareness may allow early management (eg, surgical valvuloplasty has been described); Awareness of the risk of glaucoma can allow surveillance, prompt awareness and treatment 21070929; 23322711; 24686847; 24995871; 25243380; 25620204; 30219631 IFITM5 16644 387733 Osteogenesis imperfecta, type V AD N/A N/A Craniofacial; Musculoskeletal General Pamidronate treatment has been described as beneficial in terms of reducing fracture risk, but the advantage of early (genetic) diagnosis is unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10976985; 16162424; 22863190; 22863195; 23408678; 23612438; 23674381; 23813632; 24478195; 24519609 IFNAR2 5433 3455 Immunodeficiency 45 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have immunodeficiency, and related adverse reactions to vaccinations have been reported such that awareness may help prevent morbidity 26424569 IFNG 5438 3458 Immunodeficiency 69 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be susceptible to frequent and severe mycobacterial infections, and awareness and early and aggressive treatment of infections may be beneficial; Consideration of potential adverse effects of BCG vaccination in some individuals may be beneficial 32163377 IFNGR1 5439 3459 Immunodeficiency 27B; Immunodeficiency 27A AD/AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be susceptible to frequent and severe mycobacterial infections, and awareness and early and aggressive treatment of infections may be beneficial; Consideration of potential adverse effects of BCG vaccination in some individuals may be beneficial 8960475; 8960473; 9389728; 10192386 IFNGR2 5440 3460 Immunodeficiency 28 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be susceptible to frequent and severe mycobacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 15924140; 23161749; 31222290 IFNL3 18365 282617 Drug metabolism, IL28B-related AD Pediatric General Pharmacogenomic Variants may have pharmacogenomic importance, as selection and dosing of medications (including peg-interferon and ribavirin) may be affected by the presence of variants 19684573; 19749758; 19749757; 19759533; 21254158; 21993426; 21443535; 21951981 IFT122 13556 55764 Cranioectodermal dysplasia 1; Sensenbrenner syndrome AR N/A N/A Craniofacial; Dental; Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17022080; 19760620; 20493458 IFT140 29077 9742 Short-rib thoracic dysplasia 9 with or without polydactyly AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic; Renal General Variants may modify ciliopathies due to variants in other genes; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22503633; 23418020 IFT172 30391 26160 Retinitis pigmentosa 71; Short rib thoracic dysplasia 10 with or without polydactyly AR N/A N/A Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal General In Short -rib thoracic dysplasia, renal transplantation has been desribed; Short -rib thoracic dysplasia may involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24140113; 25168386 IFT27 18626 11020 Bardet Biedl syndrome 19 AR N/A N/A Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition frequently involves multiple congenital anomalies and multisystemic manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24488770 IFT43 29669 112752 Cranioectodermal dysplasia 3; Retinitis pigmentosa 81; Short-rib thoracic dysplasia 18 with polydactyly AR N/A N/A Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21378380; 28400947; 28973684 IFT52 15901 51098 Short-rib thoracic dysplasia 16 with or without polydactyly AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26880018; 27522498 IFT57 17367 55081 Orofaciodigital syndrome XVIII AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27060890 IFT74 21424 80173 Bardet Biedl syndrome 20 AR N/A N/A Endocrine; Musculoskeletal; Neurologic; Ophthalmologic General The condition frequently involves multiple congenital anomalies and multisystemic manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27486776 IFT80 29262 57560 Craniofacial; Musculoskeletal; Neurologic; Renal AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17468754; 19610081; 19648123; 30767363 IFT81 14313 28981 Short-rib thoracic dysplasia 19 with or without polydactyly AR N/A N/A Craniofacial; Genitourinary; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27666822 IFT88 20606 8100 Ciliopathy, IFT88-related AR N/A N/A Gastrointestinal; Neurologic; Renal General Individuals may have renal and hepatic manifestations in this reported lethal disorder; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22941275 IGBP1 5461 3476 Corpus callosum, agenesis of, with mental retardation, ocular coloboma and micrognathia XL N/A N/A Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14556245 IGF1 5464 3479 Insulin-like growth factor I deficiency AR Pediatric Audiologic/Otolaryngologic; Endocrine; Neurologic Audiologic/Otolaryngologic; Endocrine Recombinant human IGF1 treatment has been reported to improve linear growth and insulin sensitivity; Interventions related to hearing impairment may also be beneficial 8857020; 10323388; 10770174; 14684690; 20668042; 21237682; 22832530 IGF1R 5465 3480 Insulin-like growth factor I, resistance to AD/AR Pediatric Endocrine Endocrine Bi-allelic variants have been described as resulting in a more severe phenotype Individuals may manifest with severe growth deficiency, and growth hormone therapy (starting at a relatively early age) can be beneficial 14657428; 22998174; 22130793; 23045302 IGF2 5466 3481 Silver-Russell syndrome 3 (Growth restriction, severe, with distinctive facies) AD Pediatric Cardiovascular; Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic Endocrine Imprinting has been implicated in the inheritance pattern Among other findings, response to growth hormone therapy has been described, and awareness may allow early diagnosis and management of this issue 26154720; 28489339; 28796236; 28848601; 30400067; 30152198; 31544945 IGFALS 5468 3483 Insulin-like growth factor-binding protein, acid-labile subunit, deficiency of AR Pediatric Endocrine Endocrine As growth hormone treatment has not been reported as being effective in this condition, genetic diagnosis may be beneficial in terms of pursuing optimal management 14762184; 17726072; 21396577; 21664162; 23488611 IGFBP7 5476 3490 Retinal arterial macroaneurysm with supravalvular pulmonic stenosis AR N/A N/A Cardiovascular; Ophthalmologic General Argon laser photocoagulation of the retinal macroaneurysms has been described as resulting in clinical improvement in some individuals; Surgical repair of pulmonic stenosis may be indicated in some individuals Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12441727; 21835307 IGHM 5541 3507 Agammaglobulinemia 1 AR Pediatric Allergy/Immunology/Infectious; Gastrointestinal Allergy/Immunology/Infectious Antiinfectious prophylaxis (including with administration of IVIG) and early and aggressive treatment of infections may be beneficial 8890099; 12370281; 21039741 IGHMBP2 5542 3508 Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11528396; 14681881; 15290238; 16458836; 16765827; 17431882; 20859832; 21353777; 22157136; 25439726; 25568292 IGKC 5716 3514 Immunoglobulin kappa light chain deficiency AR N/A N/A General General The clinical relevance of the condition is unclear 4117311; 812574; 815819; 3931219 IGLL1 5870 3543 Agammaglobulinemia 2 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis (including with administration of IVIG) and early and aggressive treatment of infections may be beneficial 9419212; 10077633; 10590911 IGSF1 5948 3547 Central hypothyroidism and testicular enlargement XL Pediatric Endocrine;Genitourinary; Neurologic Endocrine Individuals can demonstrate a number of endocrine deficiencies (including central hypothyroidism, as well as growth hormone deficiency), for which hormone replacement therapy may be beneficial 23143598 IGSF3 5950 3321 Lacrimal duct defect AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Awareness may allow early surgical treatemnt of nasolacrimal duct obstruction/dacryocystocele, which may be beneficial to avoid complications 24372406 IHH 5956 3549 Acrocapitofemoral dysplasia; Brachydactyly, type A1 AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8592325; 11455389; 12384778; 12525541; 15886999; 16871364; 17486609; 18629882; 22406540 IKBKB 5960 3551 Immunodeficiency 15A; Immunodeficiency 15B AD/AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be susceptible to severe and recurrent infections, and prophylaxis and early and aggressive treatment of infections may be beneficial; BMT/HSCT has been described in Immunodeficiency 15B 24369075; 25216719 IKBKG 5961 8517 Immunodeficiency 33; Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency; Immunodeficiency, isolated; Incontinentia pigmenti; Invasive pneumococcal disease, recurrent, isolated, 2; Ectodermal dysplasia and immune deficiency 1 XL Pediatric Allergy/Immunology/Infectious; Dental; Dermatologic; Neurologic; Ophthalmologic Allergy/Immunology/Infectious; Ophthalmologic In Ectodermal dysplasia, anhdyrotic/hypohidrotic, with immune deficiency, some individuals have been described as not responding well to preventive measures/treatment; Lung transplantation has been described In Immunodeficiency 33 (Atypical mycobacteriosis), there is evidence that considerations should be taken related to certain vaccines (eg, BCG vacine should be avoided), and recognition of potential sequelae of immunodeficiency may allow prompt diagnosis and treatment of infectious manifestations; In Immunodeficiency 33, in addition to vaccine-related considerations, treatment with IVIG has been reported as beneficial; In Ectodermal dysplasia, anhdyrotic/hypohidrotic, with immune deficiency, prophylactic measures relating to infectious complications, (eg, IVIG and antibiotics) have in some individuals been described as improving clinical status when initiated early, and prompt and aggressive treatment of infections may be beneficial; In Isolated immunodeficiency, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; In Incontinentia pigmenti, type II, which may be clinically recognizable, fluorescein angiography has been recommended in order to diagnose ischemic retina in individuals with retinal changes, and early treatment with peripheral retinal photocoagulation may reduce the risk of retinal detachment; In IKBKG-related immunodeficiency such as Invasive pneumococcal disease, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT has been described in Ectodermal dysplasia and immunodeficiency 1 117248; 8923006; 10839543; 11047757; 11590134; 11242109; 11224521; 11241484; 12588226; 15577852; 15356572; 16228229; 16333836; 16532398; 16818673; 16950813; 20301645; 20829317; 21993693; 22453515; 28993958; 29534156; 30422821; 31965418 IKZF1 13176 10320 Immunodeficiency, common variable, 13 AD Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic Individuals may be susceptible to severe and recurrent bacterial infections, and prophylaxis and early and aggressive treatment of infections may be beneficial; Acute lymphoblastic leukemia has been described, and awareness may allow early detection and management 21548011; 26981933 IKZF5 14283 64376 Thrombocytopenia 7 AD Pediatric Hematologic Hematologic Some individuals have been described with severe bleeding episodes, and awareness may allow precautions and prompt management of bleeding episodes 31217188; 32419556 IL10 5962 3586 Graft vs. host disease AD Pediatric General Pharmacogenomic In Graft vs. host disease, variants may have clinical relevance, as specific allele(s) shown to be a marker of favorable outcome following transplantation 14657422; 14657427; 20305143 IL10RA 5964 3587 Inflammatory bowel disease 28, autosomal recessive AR N/A N/A Allergy/Immunology/Infectious; Gastrointestinal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19890111; 21519361; 22476154 IL10RB 5965 3588 Inflammatory bowel disease 25, early onset, autosomal recessive AR N/A N/A Allergy/Immunology/Infectious; Gastrointestinal General HSCT has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19890111; 21519361 IL11RA 5967 3590 Craniosynostosis and dental anomalies AR N/A N/A Craniofacial; Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21741611 IL12B 5970 3593 Immunodeficiency 28; Immunodeficiency 29 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be susceptible to severe and recurrent infections, including adverse sequelae from BCG vaccination, and prophylaxis and early and aggressive treatment of infections may be beneficial 9603732; 9789052; 11753820 IL12RB1 5971 3594 Immunodeficiency 30 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described as susceptible to severe atypical mycobacterial infections (as well as other infections, including Salmonella, Cryptococcal, Coccidioides infections), and prophylaxis and early and aggressive treatment of infections may be beneficial; Consideration of potential adverse effects of BCG vaccination in some individuals may be beneficial 9603732; 9603733; 12591909; 15736007; 21905505; 21258095; 22523911; 23864330 IL17F 16404 112744 Candidiasis, familial, 6 AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may manifest with chronic cutaneous candidiasis, and awareness may allow early detection and aggressive treatment of infections may be beneficial 21350122 IL17RA 5985 23765 Immunodeficiency 51 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described as susceptible to infections such as Candida albicans, Staphlycoccal skin infections, and bacterial respiratory infections, and awareness may allow early detection and early and aggressive treatment of infections 21350122; 27930337 IL17RC 18358 84818 Candiasis, familial, 9 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described as susceptible to Candida albicansinfections, and awareness may allow early detection and early treatment of infections 25918342 IL17RD 17616 54756 Hypogonadotropic hypogonadism 18, with or without anosmia AD/Digenic Pediatric Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal; Neurologic Audiologic/Otolaryngologic; Endocrine Relatively complex genetic models of disease have been described (eg, involving variants in other FGF8-network-associated genes) In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required; Congenital hearing loss in individuals is typically (though not always) described as unilateral, and recognition and interventions related to speech and language development may be beneficial 23643382 IL18BP 5987 10068 Hepatitis, fulminant viral, suspectibility to AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious The condition has been described as involving susceptibilty to fulminant viral hepatitis as well as other autoimmune manifestations, and awareness may allow prompt and aggressive management of infectious and related sequelae 31213488 IL1RAPL1 5996 11141 Mental retardation, X-linked 21 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8230164; 10471494; 16470793; 18005360; 19012350; 18801879; 21484992 IL1RN 6000 3557 Osteomyelitis, sterile multifocal, with periostitis and pustulosis AR Pediatric Allergy/Immunology/Infectious; Dermatologic Allergy/Immunology/Infectious Individuals may present in infancy with manifestations including rash, pain, and oral lesions, which may advance to more severe findings such as progressive skin lesions, vasculitis, skeletal lesions, pulmonary disease, and severe inflammatory response syndrome, and medical treatment (eg, with anakinra) has been described as effective 19494218; 19494219 IL21 6005 59067 Immunodeficiency, common variable, 11 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described as manifesting with primary immunodeficiency (with sequelae including severe inflammatory bowel disease, as well as recurrent/severe respiratory infections) and recognition may allow prophylactic measures and early and aggressive treatment of infections 24746753 IL21R 6006 50615 Immunodeficiency, primary, autosomal recessive, IL21R-related AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may manifest with immunodeficiency, and prophylactic measures, as well as early and aggressive treatment of infections may be beneficial; HSCT has been described 23440042; 25398835 IL2RA 6008 3559 Immunodeficiency 41 with lymphoproliferation and autoimmunity AR Pediatric Allergy/Immunology/Infectious; Gastrointestinal Allergy/Immunology/Infectious Described individuals have an increased susceptibility to bacterial, fungal, and viral infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been described 9096364; 10879793 IL2RB 6009 3560 Immunodeficiency 63 with lymphoproliferation and autoimmunity AR Pediatric Allergy/Immunology/Infectious; Gastrointestinal Allergy/Immunology/Infectious Individuals have been described with immunodeficiency and immune dysregulation; immune suppression has been described as being beneficial prior to HSCT 31040184; 31040185 IL2RG 6010 3561 Combined immunodeficiency, X-linked XL Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections is indicated prior to attempts at immune reconstitution; Chronic immunoglobulin therapy may be required even after treatment aimed at immune reconstitution, which is necessary for survival; BMT/HSCT has been described, as has the use of gene therapy in individuals who are not candidates for or who have failed BMT 2243135; 7883965; 8462096; 9063412; 11517204; 11806989; 20301584; 21184155; 22460439 IL31RA 18969 133396 Amyloidois, primary localized cutaneous, 2 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19663869; 19690585 IL36RN 15561 26525 Psoriasis 14, pustular AR N/A N/A Allergy/Immunology/Infectious; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21848462; 21839423; 22903787; 23698098 IL6R 6019 3570 Hyper-IgE recurrent infection syndrome 5, autosomal recessive AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious The condition can involve early-onset recurrent and sever inffections, and awareness may allow prophylaxis and early and aggressive treatment of infections 31235509 IL6ST 6021 3572 Hyper-IgE recurrent infection syndrome 4, autosomal recessive AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Neurologic; Musculoskeletal Allergy/Immunology/Infectious Individuals have been described as being at increased risk of bacterial infections, and prophylaxis and early and aggressive treatment of infections may be beneficial 28747427; 30309848 IL7 6023 3574 Epidermodysplasia verruciformis, susceptibility to, 5 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Oncologic Allergy/Immunology/Infectious; Oncologic Individuals have been described with susceptibility to certain infections as well as potential increased risk of skin cancer, and awareness may allow prompt diagnosis and management of sequeleae 25981006 IL7R 6024 3575 Severe combined immunodeficiency, autosomal recessive, T-cell negative, B-cell positive, NK cell positive AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals are susceptible to frequent and severe bacterial, viral, fungal, and opportunistic infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT has been described 9843216; 11023514; 17827065; 21184155; 21625022; 21883749 ILDR1 28741 286676 Deafness, autosomal recessive 42 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 15641023; 21255762; 23226338 IMPA1 6050 3612 Mental retardation, autosomal recessive 59 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26416544 IMPDH1 6052 3614 Retinitis pigmentosa 10; Leber congenital amaurosis 11 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11875050; 11875049; 16384941; 20006823; 20238028; 20301475; 21791244 IMPDH2 6053 3615 IMPDH2 enzyme activity, variation in AD Pediatric Biochemical Pharmacogenomic Variants may be involved in response to treatment with medications such as mycophenolate mofetil in individuals who have undergone transplants 17496727 IMPG1 6055 3617 Macular dystrophy, vitelliform, 4 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23993198; 25085631 IMPG2 18362 50939 Retinitis pigmentosa 56 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20673862; 25085631 INF2 23791 64423 Focal segmental glomerulosclerosis 5 AD N/A Allelic with Charcot-Marie-Tooth disease, dominant intermediate E (AD) Neurologic; Renal Renal The condition can involve renal failure, and early diagnosis may enable management considerations 20023659; 21415313; 22187985; 22961558; 22971997 INPP5E 21474 56623 Joubert syndrome 1; Mental retardation, truncal obesity, retinal dystrophy, and micropenis (MORM syndrome) AR N/A N/A Endocrine; Genitourinary; Neurologic; Ophthalmologic; Renal General Individuals may have renal issues (though most reported individuals did not have evidence of compromised renal function) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16493448; 19668216; 19668215 INPP5K 33882 51763 Muscular dystrophy, congenital, with cataracts and intellectual disability (MDCCAID) AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28190456; 28190459 INPPL1 6080 3636 Opsismodysplasia AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Musculoskeletal; Pulmonary; Renal Allergy/Immunology/Infectious; Cardiovascular; Pulmonary; Renal The condition can involve multiple congenital anomalies The condition may involve renal phosphate wasting in some individuals, and prompt detection may allow beneficial dietary/medical management; Many individuals manifest with respiratory insufficiency and frequent respiratory infections, and awareness may allow prompt diagnosis and treatment; Individuals may also demonstrate congenital anomalies affecting the cardiovascular, renal, and other systems, and awareness may allow early detection and management 12624139; 23273567; 23273569; 27708270 INS 6081 3630 Diabetes mellitus, permanent neonatal 4 AD Pediatric Allelic with Hyperproinsulinemia, familial, with or without diabetes (AD); Maturity onset diabetes of the young (AD) Endocrine Endocrine Individuals may manifest in infancy with findings including intrauterine growth retardation, postnatal growth deficiency, and signs of diabetes mellitus (eg, hyperglycemia, glycosuria), as well as severe dehydration, and recognition can allow preventive measures related to potential sequelae, surveillance (eg, with blood glucose monitoring as well as surveillance for other common sequelae of diabetes mellitus affecting systems such as the renal and ophthalmogic systems); In the case of an acute diabetic crisis, rapid treatment (eg, with rehydration and IV insulin, transitioning to SQ insulin when stable) is indicated, though rapid-acting and (non-continuous) short-acting insulin preparations may result in severe hypoglycemia in young patients 815812; 288074; 381941; 6424111; 3512591; 17855560; 18451997; 18162506; 18192540; 18171712; 20301620 INSL3 6086 3640 Cryptorchidism AD N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11095425; 12601553; 12970298; 17028442; 17437853; 19416190 INSR 6091 3643 Hyperinsulinemic hypoglycemia, familial, 5; Rabson-Mendenhall syndrome; Donohoe syndrome AD/AR Pediatric Allelic with Diabetes mellitus, insulin-resistant, with acanthosis nigricans (AD/AR) Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Dental; Dermatologic; Endocrine; Musculoskeletal; Oncologic; Renal Allergy/Immunology/Infectious; Cardiovascular; Endocrine; Oncologic; Renal Several affected individuals with familial hyperinsulinemic hypoglycemia have had severe sequelae, such as hypoglycemia-induced seizures, which could potentially be averted by early recognition and treatment; In Rabson-Mendenhall syndrome, due to the risk of infectious sequelae, early and aggressive treatment of infections can be beneficial; In Rabson-Mendenhall syndrome, effective treatment of insulin resistance can be difficult, but there are reports of the efficacy of leptin treatment; In Donohoe syndrome, medical (eg, diazoxide) and surgical treatments may be beneficial; Recognition may allow prompt treatment of other organ system involvement, such as related to cardiac manifestations (eg, cadiac hypertrophy, as recombinant human insulin-like growth factor-1 hs been reported as beneficial for treatment of hypertrophic cardiomyopathy and renal tubular dysfunction); Individuals with Donohue syndrome or Rabson-Mendenhall syndrome may be at increased risk of malignant processes (eg, breast and thyroid cancer have been described), and awareness may allow prompt detection and early treatment 13212592; 13302174; 2121734; 2544998; 3020345; 3322162; 3384956; 3415309; 3721065; 7815442; 8105179; 8288049; 8326490; 15070911; 15161766; 15232309; 17201797; 18405695; 18411068; 21869538; 22172957; 22563226; 22768670; 22972224; 23229189; 23347304; 23824322 INTS1 24555 26173 Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28542170; 30622326; 31428919 INTU 29239 27152 Orofaciodigital syndrome XVII; Short-rib throacic dysplasia 20 with polydactyly AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27158779 INVS 17870 27130 Nephronophthisis 2 AR N/A N/A Cardiovascular; Gastrointestinal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2702088; 9792867; 12872123; 19177160; 20798123; 23559409 IPMK 20739 253430 Small intestinal carcinoid, hereditary AD Pediatric Oncologic Oncologic Individuals have been described as at high risk of small intestinal carcinoid tumors, and awareness may allow surveillance and prompt management 25865046 IQCB1 28949 9657 Senior-Loken syndrome 5 AR N/A N/A Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15723066; 21220633; 23661368 IQCE 29171 23288 Postaxial polydactyly, type A7 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28488682 IQSEC1 29112 9922 Intellectual developmental disorder with short stature and behavioral abnormalities AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31607425 IQSEC2 29059 23096 Mental retardation, X-linked 1 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7943039; 3177466; 20473311 IRAK4 17967 51135 Immunodeficiency 67 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 12637671; 15069404; 16647421; 17893200; 21734245; 26825884 IREB2 6115 3658 Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30915432 IRF2BP2 21729 359948 Immunodeficiency, common variable, 14 AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 27016798 IRF2BPL 14282 64207 Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30057031 IRF3 6118 3661 Encephalopathy, acute, infection-induceed (herpes-specific), susceptibility to, 7 AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be susceptible to severe herpes simplex virus infections includingherpes encephalitis has been described, and awareness may allow early diagnosis and treatment, potentially decreasing morbidity and mortality 26216125 IRF4 6119 3662 Skin/hair/eye pigmentation, variation in, 8 AD N/A N/A Dermatologic General Though potentially related to melanoma susceptibility, the clinical relevance of the condition is unclear 17952075; 18483556; 19710684; 20602913; 24267888 IRF6 6121 3664 Popliteal pterygium syndrome; van der Woude syndrome 1; Orofacial cleft 6 AD N/A N/A Craniofacial; Dermatologic; Genitourinary; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Variants may additionally act as susceptibility factors (rather than being involved in Mendelian-inherited dominant disease) 13158329; 6573981; 2164325; 7628117; 10593995; 12219090; 14757865; 15317890; 16096995; 15558496; 17539900; 18247422; 18478600; 18836445; 20803643; 20799332; 21045959; 21082654; 21468557; 21739575; 21995291; 22488974; 24442519 IRF7 6122 3665 Immunodeficiency 39 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious An individual has been described as developing severe respiratory distress following influenza infection, and awareness may allow preventive measures and rapid management 25814066 IRF8 5358 3394 Immunodeficiency 32A (CD11C-positive/CD1C-positive dendritic cell deficiency); Immunodeficiency 32B (monocyte and dendritic cell deficiency) AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals with Immunodeficiency 32A (CD11C-positive/CD1C-positive dendritic cell deficiency) have been described as demonstrating disseminated BCG disease that was amenable to treatment, and preventive measures, as well as prompt treatment of infection, may be beneficial; Individuals with Immunodeficiency 32B (monocyte and dendritic cell deficiency) demonstrate immunodeficiency, with severe opportunistic infections, and prophylactic measures and prompt and aggressive treatment of infections may be beneficial; HSCT has been described 21524210 IRF9 6131 10379 Immunodeficiency 65 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described with early-onset severe and recurrent viral infections, and antiinfectious prophylaxis (intravenous immunoglobulin has been described) and early and aggressive treatment of infections may be beneficial; live attenuated vaccines have been reported as resulting in poor outcomes in patients with impaired interferon responses 30143481; 30826365 IRS4 6128 8471 Hypothyroidism, congenital, nongoitrous, 9 XL Pediatric Endocrine Endocrine The condition can manifest with early clinical signs, of hypothyroidism, and treatment with thyroid hormone replacement has been reported 30061370 ISCA1 28660 81689 Multiple mitochondrial dysfunctions syndrome 5 AR N/A N/A Biochemical; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Variants may additionally act as susceptibility factors (rather than being involved in Mendelian-inherited dominant disease) 28356563; 29767723 ISCA2 19857 122961 Multiple mitochondrial dysfunctions syndrome 4 AR N/A N/A Biochemical; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Variants may additionally act as susceptibility factors (rather than being involved in Mendelian-inherited dominant disease) 25539947 ISCU 29882 23479 Myopathy with lactic acidosis, hereditary AR Pediatric Cardiovascular; Musculoskeletal; Renal Musculoskeletal; Renal Treatment (using an antisense phosphorodiamidate morpholino oligonucleotide) of cultured fibroblasts from three individuals with a homozygous splice-site variant resulted in restoration of the normal splicing pattern In addition to cardiovascular features, the condition can include rhabdomyolysis, and appropriate precautions and prompt recognition may be beneficial 14213465; 5811159; 2384736; 18304497; 18296749; 19846308; 20206689 ISG15 4053 9636 Immunodeficiency 38, with basal ganglia calcification AR Pediatric Allergy/Immunology/Infectious; Neurologic Allergy/Immunology/Infectious Individuals may sufffer from severe infections (including Mycobacterial and Salmonella), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BCG vaccine has been reported as resulting in adverse reactions 22859821; 25307056 ITCH 13890 83737 Autoimmune disease, syndromic multisystem, with facial dysmorphism AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Endocrine; Gastrointestinal; Neurologic; Pulmonary Allergy/Immunology/Infectious; Endocrine Individuals typically present with multisystem malformations, which may aid in clinical recognition, but awareness of disease may allow corticosteroid and other related immunosuppressive treatment related to autoimmune manifestations (including hypothyroidism, which responds to standard hormone replacement therapy), as well as awareness of the risk of frequent infections, which can allow prophylaxis/surveillance for infectious diseases, and early and aggressive treatment of infections 20170897 ITGA2B 6138 3674 Bleeding disorder, platelet-type, 16, autosomal dominant; Glanzmann thrombasthenia 1 AD/AR Pediatric Hematologic Hematologic Individuals with Bleeding disorder, platelet-type, 16 may have mild disease, but awareness may allow prompt diagnosis, allowing preventive measures and rapid treatment of bleedin episodes; Individuals with Glanzmann thrombasthenia can have severe bleeding diatheses, and preventive measures as well as rapid treatment (which can include local measures as well as platelet transfusions, recombinant activated factor VII, and octreotide for GI bleeding) can be beneficial; Precipitating factors should be avoided 2014236; 8282784; 16463284; 19408193; 20020534; 21454453; 21917754; 22102273; 21487445; 22250950; 22513797 ITGA3 6139 3675 Interstitial lung disease with nephrotic syndrome and epidermolysis bullosa AR N/A N/A Dermatologic; Pulmonary; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22512483; 25810266 ITGA6 6142 3655 Epidermolysis bullosa, junctional, with pyloric stenosis AR N/A N/A Dermatologic; Gastrointestinal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9185503; 9158140; 11251584; 20301336 ITGA7 6143 3679 Muscular dystrophy, congenital, due to integrin alpha-7 deficiency AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9590299; 19260934 ITGA8 6144 8516 Renal hypodysplasia/aplasia 1 AR N/A N/A Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24439109 ITGB2 6155 3689 Leukocyte adhesion deficiency, type I AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals frequently first present with umbilical cord stump infection, and are prone to recurrent and severe bacterial infections, such that antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been described as effective 52003; 86829; 7310581; 7259263; 6718115; 6096477; 3703627; 2877234; 3510003; 2880869; 3234429; 3279017; 1972597; 7902162; 17244687; 19864007; 20351460; 20549317 ITGB3 6156 3690 Bleeding disorder, platelet-type, 24, autosomal dominant; Glanzmann thrombasthenia 2; Thrombocytopenia, neonatal alloimmune AD/AR Pediatric Hematologic Hematologic Bi-allelic variants have been described as resulting in a more severe phenotype; Specific variants may also be important in neonatal alloimune thrombocytopenia (as relates to platelet transfusions) Individuals with dominant disease may demonstrate moderate to severe bleeding, and awareness may allow preventive measures and prompt management; Precipitating factors for bleeding episodes should be avoided (for both dominant and recessive disease forms); Individuals with bi-allelic variants can have severe bleeding diatheses, and preventive measures as well as rapid treatment (which can include local measures as well as platelet transfusions, recombinant activated factor VII, and octreotide for GI bleeding) can be beneficial; Variants may be relevant to potential reactions from platelet transfusion, and knowledge may have relevance to related treatment 7193688; 2257303; 2428841; 2565345; 1967954; 2257303; 2392682; 2014236; 1371279; 1438206; 1602006; 1430225; 8093349; 8471765; 7694683; 8878424; 9160670; 9351872; 9845537; 9700201; 10583927; 10559451; 11425767; 11723016; 16721604; 16463284; 18065693; 19336737; 19408193; 20020534; 20081061; 20345392; 21917754; 22102273; 22250950; 22890234; 23146053; 23253071; 23929305 ITGB4 6158 3691 Epidermolysis bullosa, junctional, with pyloric atresia; Epidermolysis bullosa, junctional, non-Herlitz type; Epidermolysis bullosa simplex, Weber-Cockayne type AD/AR N/A N/A Dermatologic; Gastrointestinal; Renal Renal In addition to gastrointestinal anomalies, the condition may include ureterovesical obstruction, and prompt recognition and treatment may be beneficial in terms of renal function 6177243; 7545057; 9674902; 9792864; 10484780; 10792571; 12485428; 18348258; 20301336; 20955205; 21969027; 22354727; 22674212 ITGB6 6161 3694 Amelogenesis imperfecta, type IH AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24305999; 24319098 ITK 6171 3702 Lymphoproliferative syndrome 1 AR Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic Individuals may also have related predisposition to infectious complications Due to the risk of malignancy, surveillance may allow prompt treatment; Medical treatment (eg, chemotherapy, virostatic agents, corticosteroids, rituximab) may induce remission, but treatment with HSCT may be required; Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 19425169; 21109689; 22289921; 22487848 ITM2B 6174 9445 Cerebral amyloid angiopathy; Dementia, familial Danish; Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities AD N/A N/A Audiologic/Otolaryngologic; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21610757; 7086452; 2364266; 10391242; 10781099; 11557758; 21048150; 24026677 ITPA 6176 3704 Inosine triphosphatase deficiency AR Pediatric Allelic with Developmental and epileptic encephalopathy 35 (AR) Biochemical; Neurologic Pharmacogenomic Abnormal 6-mercaptopurine metabolism in ITPase-deficient patients may cause thiopurine drug toxicity 1204209; 12384777; 17697198; 19214663; 19631656; 19682085; 26224535 ITPR1 6180 3708 Gillespie syndrome; Spinocerebellar ataxia 15; Spinocerebellar ataxia 29 AD/AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11445634; 11723290; 12828938; 14981189; 17030759; 17558851; 17590087; 18579805; 17932120; 21555639; 21367767; 21827915; 22318346; 22986007; 27108797; 27108798 ITPR2 6181 3709 Anhidrosis, isolated, with normal sweat glands (Dann-Epstein-Sohar syndrome) AR Pediatric Dermatologic Dermatologic Individuals have been described as manifesting with severe heat intolerance, and awareness can allow measures to help control temperature in order to decrease potential sequelae 25329695 IVD 6186 3712 Isovaleric acidemia AR Pediatric Biochemical; Cardiovascular; Neurologic Biochemical Medical/dietary treatment (eg, with l-carnitine, glycine, and leucine restricted/low protein diet) can be effective; Specific measures can be taken to prevent severe sequelae of acute metabolic decompensation 5229850; 4378266; 4166104; 692626; 6630517; 3863140; 3139936; 3137519; 2063866; 15486829; 20142522; 20301313; 20662350; 20807522; 21207059; 21335445; 22004070; 22350545; 22960500; 23063737 IVNS1ABP 16951 10625 Immunodeficiency 70 AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be at increased risk of recurrent infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 32499645 IYD 21071 389434 Thyroid dyshormonogenesis 4 AR Pediatric Endocrine Endocrine In heterozygotes, clinical hypothyroidism has been described as arising at a later age than in individuals with biallelic variants Individuals may present with clinical signs and sequelae of childhood hypothyroidism, which can lead to long-term neurologic and other effects, and medical treatment of hypothyroidism (eg, with T4) can be beneficial 18765512; 18434651; 22535972 JAG1 6188 182 Alagille syndrome; Deafness, congenital heart defects, and posterior embryotoxon AD Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Renal Liver transplantation has been described For Alagille syndrome, individuals may have hepatic complications, and medications (eg, ursodeoxycholic acid, cholestyramine), and, when necessary, partial external biliary diversion may be beneficial; Other treatments, such as fat-soluble vitamin supplementation may be beneficial; Surveillance for other manifestations, including cardiac and renal manifestations, may be beneficial in order to allow early diagnosis and treatment and/or preventive measures; Contact sports should be avoided; For Deafness, congenital heart defects, and posterior embryotoxon, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 803282; 9039994; 9207788; 9207787; 9585603; 9700188; 9890073; 10590916; 10213047; 11152664; 11313761; 11511567; 11139239; 12022040; 12244552; 12239725; 12509572; 14993126; 16013021; 16573599; 17286312; 19597493; 19948535; 20301450; 20437614; 22040217; 22105858; 22488849; 22521120; 22759690; 22937766; 23752887; 23801938; 23956173 JAGN1 26926 84522 Neutropenia, severe congenital, 6, autosomal recessive AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may sufffer from severe, recurrent bacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported 25129144 JAK1 6190 3716 Autoinflammation, immune dysregulation, and eosinophilia AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described as being affected by manifestations such as atopic dermatitis and chronic gastrointestinal inflammation, and medical management (with JAK inhibitors such as ruxolitinib and tofacitinib) has been described as clinically beneficial 28111307; 32750333 JAK2 6192 3717 Thrombocythemia 3 AD Adult Variants may be involved in predisposition to and pathogenesis of oncologic processes (AD) Hematologic Hematologic Individuals may be at high risk of thrombosis, and preventive measures and early treatment of manifestations may be beneficial 16762626; 16707754; 17989398; 19036091; 19287384; 19287385; 19338077; 19847199; 22397670; 22696908; 22571758 JAK3 6193 3718 Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, natural killer cell-negative AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported as effective for T-cell reconstitution, but less succesful as relates to B and NK-cell function 7659163; 7481768; 14615376; 21184155; 21732012; 23001410 JAM2 14686 58494 Basal ganglia calcification, idiopathic, 8, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31851307; 32142645 JAM3 15532 83700 Hemorrhagic destruction of the brain, subependymal calcification, and cataracts AR N/A N/A Cardiovascular; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21109224; 23255084 JPH2 14202 57158 Cardiomyopathy, familial hypertrophic 17 AD Pediatric Cardiovascular Cardiovascular Surveillance and preventive measures, including medical management, may reduce morbidity 17476457; 17509612; 22515980 JPH3 14203 57338 Huntington disease-like 2 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11694876; 11761463; 11914418; 11940688; 12805114; 14557581; 18816802; 19735092; 22367996; 22971727 JUP 6207 3728 Arrhythmogenic right ventricular dysplasia, familial, 12; Naxos disease AD/AR Adult Cardiovascular; Dermatologic Cardiovascular Dermatologic findings may be apparent in Naxos disease, but cardiac association may not be readily appreciated Individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation 2945574; 10902626; 17924338; 20301310; 22527912; 24460197 KANK1 19309 23189 Cerebral palsy, spastic quadriplegic, 2 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16301218 KANK2 29300 25959 Nephrotic syndrome 16; Palmoplantar keratoderma and woolly hair AR N/A N/A Dermatologic; Musculoskeletal; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11874502; 24671081; 25961457 KANSL1 24565 284058 Koolen-de Vries syndrome AD N/A N/A Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22482802; 22544363; 26306646; 28440867 KARS1 6215 3735 Deafness, autosomal recessive 89 AR Pediatric Allelic with Charcot-Marie-Tooth disease, recessive intermediate B (AR) Audiologic/Otolaryngologic; Neurologic Audiologic/Otolaryngologic Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20920668; 23768514 KAT5 5275 10524 Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities AD Pediatric Craniofacial; Genitourinary; Neurologic; Renal Renal Among other features, indivbiduals have been described with renal anomalies that may result in recurrent urinary tract infections, and awareness may allow early diagnosis and management, which may help preserve renal function 32822602 KAT6A 13013 7994 Arboleda-Tham syndrome AD Pediatric N/A Cardiovascular; Craniofacial; Dental; Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary Cardiovascular; Gastrointestinal Due to the risk of cardiovascular involvement, screening (with ECG and echocardiogram) has been recommended to ascertain and enable management of cardiovascular sequelae (which may require surgical intervention); Individuals have been described as having increased risk of intestinal malrotation and bowel obstruction, and awareness may allow prompt interventions if these sequelae occur 25728775; 25728777; 27133397; 30245513 KAT6B 17582 23522 Ohdo syndrome, SBBYS variant; Genitopatellar syndrome AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Dental; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal Audiologic/Otolaryngologic; Endocrine The conditions can involve multiple congenital anomalies Among other manifestations, individuals may demonstrate early-onset hypothyroidism, and appropriate management may be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12210329; 12210330; 12949978; 16761293; 21412151; 22077973; 22265014; 23236640; 23436491 KAT8 17933 84148 Li-Ghorbani-Weisz-Hubshman AD N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31794431 KATNB1 6217 10300 Lissencephaly 6, with microcephaly AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25521378; 25521379 KATNIP 29068 23247 Joubert syndrome 26 AR Pediatric Endocrine; Neurologic Endocrine Individuals have been described with panhypopituitarism, and awareness may allow early diagnosis and medical management (eg, with hormone replacement therapy) 26714646 KBTBD13 37227 390594 Nemaline myopathy 6 AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11731279; 21104864; 21109227 KCNA1 6218 3736 Episodic ataxia, type 1/myokymia syndrome AD Pediatric Neurologic; Renal Renal For episodic ataxia medical treatment (eg, with phenytoin) may be effective, but the benefit of an early (genetic) diagnosis is unclear Individuals can have severe hypomagnesemia, which is responsive to magnesium therapy 7842011; 11026449; 17136396; 19307729 KCNA2 6220 3737 Developmental and epileptic encephalopathy 32 AD N/A N/A Neurologic General As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25477152; 25751627 KCNA4 6222 3739 Microcephaly, cataracts, impaired intellectual development, and dystonia with abnormal striatum AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23181898; 27582084 KCNA5 6224 3741 Atrial fibrillation, familial, 7 AD Adult Cardiovascular Cardiovascular Surveillance for and medical intervention to prevent morbidity related to atrial fibrillation may be beneficial 16772329; 17266934; 19343045; 20638934 KCNB1 6231 3745 Epileptic encephalopathy, early infantile, 26 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25164438 KCNC1 6233 3746 Epilepsy, progressive myoclonic 7 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25401298 KCNC3 6235 3748 Spinocerebellar ataxia 13 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16501573 KCND3 6239 3752 Brugada syndrome 9 AD Pediatric Allelic with Spinocerebellar ataxia 19 (AD); Spinocerebellar ataxia 22 (AD) Cardiovascular; Neurologic Cardiovascular Individuals have been described as manifesting with arrhythmias and sudden cardiac death, and early diagnosis may allow management (such as with ICD placement) 21349352; 22457051; 23280837; 23280838 KCNE1 6240 3753 Long QT syndrome 5; Jervell and Lange-Nielsen syndrome 2 AD/AR/Digenic Pediatric Audiologic/Otolaryngologic; Cardiovascular Audiologic/Otolaryngologic; Cardiovascular Heterozygous variants cause long QT-syndrome 1 (Ward Romano syndrome); Biallelic variants cause Jervell and Lang-Nielsen syndrome, which includes congenital deafness; Digenic/complex inheritance has been reported Preventive measures and medical management may be helpful to help decrease morbidity related to long-QT syndrome; In JLNS, treatment of deafness may also be beneficial for language and related development 13435203; 6991948; 9354802; 9328483; 10973849; 15051636; 14760488; 15840476; 16922724; 20301308; 20301579; 20809527; 21070882 KCNE2 6242 9992 Long QT syndrome 6; Atrial fibrillation, familial 4 AD Pediatric Cardiovascular Cardiovascular; Pharmacogenomic Digenic/complex inheritance has been reported In Long QT syndrome, in order to prevent sequelae including syncope, cardiac arrest and sudden death prophylactic use of beta blockers in asymptomatic individuals may be beneficial; ICD may be indicated for individuals refractory to beta-blocker treatment or with history of cardiac arrest; Agents that can contribute to prolonged QT or related dysrhythmias should be avoided, as should activities associated with high stress/intense exertion; In Atrial fibrillation, surveillance and risk awareness can allow early detection and medical treatment of disease, including related sequelae (eg, thromboembolic events) 10219239; 10973849; 15368194; 15840476; 16922724; 20301308; 20809527 KCNE3 6243 10008 Brugada syndrome 6 AD Pediatric Cardiovascular Cardiovascular; Pharmacogenomic Surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever 12414843; 14504341; 15037716; 15212652; 19122847; 19306396; 19606473; 20301690; 22397033; 22987075 KCNH1 6250 3756 Temple-Baraitser syndrome; Zimmermann-Laband syndrome 1 AD/AR N/A N/A Craniofacial; Dental; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18203178; 20683999; 23994350; 24357613; 25420144; 25915598 KCNH2 6251 3757 Long QT syndrome 2; Short QT syndrome 1 AD Pediatric Cardiovascular Cardiovascular Digenic/complex inheritance has been reported In Long QT syndrome, medical/surgical management (eg, with beta-blockers or ICD placement) may help prevent/decrease severe sequelae; Activities (eg, stress, certain types of physical activity) or agents (eg, certain medications) that contribute to further QT interval prolongation should be avoided; In Short QT syndrome, medical/surgical management (eg, with antiarrhythmics or ICD placement) may help prevent/decrease severe sequelae 9753711; 9694858; 9927398; 9950666; 11173780; 12925462; 14676148; 15280551; 16132053; 15828882; 15890322; 15840476; 11854117; 16075043; 16922724; 19926013; 20301308; 20809527; 21070882; 21130771; 21440677; 22382559; 22821100; 22882672; 23010577; 23098067 KCNJ1 6255 3758 Bartter syndrome, antenatal, type 2 AR Pediatric (and prenatal) Renal Renal Prenatal therapy has been reported as being beneficial; In infants, specific medications (eg, COX2 inhibitors) have been reported as beneficial; Correction of hypokalemic alkalosis can be beneficial 841184; 9002665; 10049979; 10979805 KCNJ10 6256 3766 Deafness, autosomal recessive 4, with enlarged vestibular aqueduct; Pendred syndrome, digenic; Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SESAME syndrome) AR/Digenic Pediatric Audiologic/Otolaryngologic; Neurologic; Renal Audiologic/Otolaryngologic; Renal Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalances manifests with deafness, as well as electrolyte abnormalities; Digenic inheritance has been reported Individuals with Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalances display early-onset electrolyte abnormalities (eg, hypokalemia, metabolic alkalosis, and hypomagnesemia due to renal salt wasting), and treatment related to electrolyte imbalances may be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 19420365; 19289823; 19289823; 19426954; 21849804 KCNJ11 6257 3767 Hyperinsulinemic hypoglycemia, familial, 2; Diabetes mellitus, transient neonatal, 3; Diabetes, permanent neonatal 2; Diabetes, permanent neonatal, with neurologic features AD/AR Pediatric Allelic with Maturity-onset diabetes of the young 13 (AD); Focal adenomatous hyperplasia (AD, paternally-inherited) Endocrine; Neurologic Endocrine Individuals may manifest in infancy with findings including intrauterine growth retardation, postnatal growth deficiency, and signs of diabetes mellitus (eg, hyperglycemia, glycosuria), as well as severe dehydration, and recognition can allow preventive measures related to potential sequelae, surveillance (eg, with blood glucose monitoring as well as surveillance for other common sequelae of diabetes mellitus affecting systems such as the renal and ophthalmogic systems); In the case of an acute diabetic crisis, rapid treatment (eg, with rehydration and IV insulin, transitioning to SQ insulin when stable) is indicated, though rapid-acting and (non-continuous) short-acting insulin preparations may result in severe hypoglycemia in young patients; Individuals with neonatal diabetes mellitus due to KCNJ11 variants may specifically respond well to oral sulfonylurea treatment 8923010; 9356020; 11395395; 15115830; 15579781; 15531505; 15562009; 15718250; 15998776; 15784703; 16731833; 16885550; 17327377; 17213273; 18556340; 18596924; 19357197; 20022885; 20049716; 20301620; 20546268; 22701567 KCNJ13 6259 3769 Snowflake vitreoretinal degeneration; Leber congenital amaurosis 16 AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4812083; 15557460; 18179896; 18309337; 21763485 KCNJ18 39080 100134444 Thyrotoxic periodic paralysis, susceptibility to AD Pediatric Endocrine Endocrine Treatment of underlying hyperthyroidism is an effective treatment 16608889; 20074522; 21665951 KCNJ2 6263 3759 Atrial fibrillation, familial 9; Short QT syndrome 3; Andersen syndrome; Long QT syndrome 7 AD Pediatric Cardiovascular; Musculoskeletal Cardiovascular Depending on the cardiac phenotype, specific medical intervention to prevent morbidity and mortality related to arrhythmias can be beneficial; Surveillance for cardiac events is indicated 4106724; 5007210; 8080508; 9307251; 10406668; 11371347; 12148092; 12177393; 12086641; 12163457; 12796536; 15761194; 15890322; 16217063; 15922306; 16571646; 16419128; 16769944; 17324964; 17211524; 19931173; 20111058; 20301441; 20382953; 20809527; 21148745; 21493816; 21875779; 22155372; 22589293 KCNJ3 6264 3760 Leber congenital amaurosis 16 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21763485; 25475713; 25921210 KCNJ5 6266 3762 Long QT syndrome 13; Hyperaldosteronism, familial, type III AD Pediatric Cardiovascular; Endocrine Cardiovascular; Endocrine In Long QT syndrome, preventive measures and medical management may be helpful to help decrease morbidity; sudden death in infancy has been reported; In Hyperaldosteronism, familial, hypertension and aldosteronism are not reversed by administration of exogenous glucocorticoids and patients require adrenalectomy 18505761; 20301308; 20560207; 21311022; 22447138; 22628607; 24574546 KCNJ6 6267 3763 Keppen-Lubinsky syndrome AD N/A N/A Craniofacial; Endocrine; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12567423; 19610118; 25620207 KCNK18 19439 338567 Migraine, with or without aura, susceptibility to, 13 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20871611 KCNK3 6278 3777 Pulmonary hypertension, primary, 4 AD Pediatric Cardiovascular; Pulmonary Cardiovascular; Pulmonary While prognosis is overall poor, medical therapy may be beneficial, though heart/lung transplantation may be required; Control of complications may be beneficial 23883380 KCNK4 6279 50801 Facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth syndrome AD N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30290154 KCNK9 6283 51305 Birk-Barel syndrome AD N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18678320 KCNMA1 6284 3778 Epilepsy, idiopathic generalized, susceptibility to, 16; Liang-Wang syndrome; Paroxysmal nonkinesigenic dyskinesia 3 with or without generalized epilepsy; Cerebellar atrophy, developmental delay, and seizures AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15937479; 27567911; 29330545; 31152168 KCNN3 6292 3782 Zimmermann-Laband syndrome 3 AD N/A N/A Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31155282 KCNN4 6293 3783 Dehydrated hereditary stomatocytosis 2 AD Pediatric Hematologic Hematologic Individuals have been described with severe anemia, and interventions such as RBC transfusions, erythropoietin, and splenectomy may be indicated 26148990; 26178367; 26198474 KCNQ1 6294 3784 Long QT syndrome 1; Jervell and Lange-Nielsen syndrome 1; Short QT syndrome 2; Atrial fibrillation, familial 3 AD/AR/Digenic Pediatric Audiologic/Otolaryngologic; Cardiovascular Audiologic/Otolaryngologic; Cardiovascular The age of onset of clinical manifestations may be highly variable; The condition can manifest with hearing loss in JLNS1 in addition to cardiac manifestations; Digenic inheritance (eg, with KCNH2) has been described Medical/surgicalmanagement (eg, ICD placement, antiarhythymognic medications) may help prevent/decrease severe sequelae, though cardiac transplantion has been necessary for some individuals; For individuals with JLNS1, recognition and prompt treatment of hearing loss may be beneficial 13435203; 4393533; 112730; 7365362; 6991948; 7471361; 1884444; 8892796; 8872472; 8528244; 9020846; 9164812; 9702906; 9593563; 9753711; 10086971; 10077519; 10220144; 10973849; 11140949; 11289718; 11479253; 11433047; 12522251; 12736279; 15159330; 15051636; 16132053; 15890322; 15840476; 16461811; 16922724; 18580685; 19261104; 20301308; 20301579; 21185499; 21952006; 22293141; 22456477; 22708720; 22727609; 22882672; 22885918; 23000022 KCNQ1OT1 6295 10984 Beckwith-Wiedemann syndrome AD Pediatric Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Renal Endocrine; Oncologic The condition can involve imprinting defects affecting the gene (an antisense transcript for KCNQ1). In Beckwith-Wiedemann syndrome, surveillance and early detection of and treatment for malignancy may decrease morbidity and mortality; Recognition and surveillance for and treatment of neonatal hypoglycemia can be beneficial 11181570; 12019213; 12772698; 20301568; 20803657; 21920939 KCNQ2 6296 3785 Epileptic encephalopathy, early infantile, 7 AD Pediatric Allelic with Seizures, benign familial neonatal 1 (AD); Myokymia (AD) Neurologic Neurologic Individuals may manifest with seizures, and specific knowledge of the underlying cause can help direct selection of optimal therapies for management based on the genetic etiology 7980108; 9430594; 9425895; 11572947; 12742592; 15249611; 16235065; 16966552; 17675531; 17872363; 19822871; 22169383; 22275249; 22884718; 22926866; 28331464 KCNQ3 6297 3786 Seizures, benign familial neonatal, 2 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1859177; 8102508; 9425900; 20437616; 22612257 KCNQ4 6298 9132 Deafness, autosomal dominant 2A AD N/A N/A Audiologic/Otolaryngologic General The onset of deafness appears postlingual Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10369879; 10025409; 16596322; 18030493; 23399560; 23443030; 23451214; 23717403 KCNQ5 6299 56479 Mental retardation, autosomal dominant 46 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28669405 KCNT1 18865 57582 Epilepsy, nocturnal frontal lobe, 5; Developmental and epileptic encephalopathy 14 AD Pediatric Neurologic Neurologic Individuals may manifest with seizures, and specific knowledge of the underlying cause can help direct selection of optimal therapies for management based on the genetic etiology 18479385; 23086396; 23086397; 23599387; 28331464 KCNT2 18866 343450 Epileptic encephalopathy, early infantile, 57 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing 29069600 KCNV2 19698 169522 Retinal cone dystrophy 3B AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16909397 KCTD17 25705 79734 Dystonia 26, myoclonic AD N/A N/A Neurologic General Surgery with pallidal deep brain stimulation has been described as beneficial, though the impact of early diagnosis is unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25983243 KCTD7 21957 154881 Epilepsy, progressive myoclonic 3, with or without intracellular inclusions AR N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing 17455289; 22606975; 22638565; 22693283; 22748208 KDELR2 6305 11014 Osteogenesis imperfecta, type XXI AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing 33053334; 33964184 KDF1 26624 126695 Ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type AD N/A N/A Craniofacial; Dental; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing 27838789 KDM1A 29079 23028 Cleft palate, psychomotor retardation, and distinctive facial features AD N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing 24838796; 26656649 KDM3B 1337 51780 Diets-Jongmans syndrome AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic Audiologic/Otolaryngologic; Oncologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Multiple patients were ascertained from a cohort of children with cancer, and a potential elevated risk of cancer may indicate that awareness may allow early diagnosis and management of oncologic sequelae 29351919; 30929739 KDM4B 29136 23030 Intellectual developmental disorder, autosomal dominant 65 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing 33232677 KDM5B 18039 10765 Mental retardation, autosomal recessive 65 AD/AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Heterozygous variants appear to be able to cause an incompletely penetrant phenotype Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing 29276005; 30409806 KDM5C 11114 8242 Mental retardation, X-linked, syndromic, Claes-Jensen type XL N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10982473; 15586325; 16538222; 18697827; 18203167; 19826449; 21575681; 22326837; 22611640 KDM6A 12637 7403 Kabuki syndrome 2 XL N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22197486; 23076834; 24633898 KDM6B 29012 23135 Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31124279 KDSR 4021 2531 Erythrokeratodermia variabilis et progressiva 4 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28575652 KEL 6308 3792 Blood group, Kell system BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 7849312; 11134029; 12842980; 15373667; 16423827 KERA 6309 11081 Cornea plana 2, autosomal recessive AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10802664; 11726611; 15370545; 17679937 KHDC3L 33699 154288 Hydatidiform mole, recurrent, 2 AR Pediatric Obstetric; Oncologic Obstetric; Oncologic Women are likely to have pregnancies with hydatidiform moles, with a high risk of persistent trophoblastic disease, including requiring chemotherapeutic treatment, and awareness may allow reproductive planning and/or surveillance measures, which may allow early detection and treatment 11932746; 19246479; 21623199; 21885028 KHK 6315 3795 Fructosuria, essential AR N/A N/A Biochemical General The clinical relevance of the condition is unclear 13759156; 14063525; 6268573; 7816517; 7833921 KIAA0586 19960 9786 Joubert syndrome 23; Short rib thoracic dysplasia 14 with polydactyly AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General The conditions can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26096313; 26166481; 26386044 KIAA0753 29110 9851 Orofaciodigital syndrome XV AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26643951 KIAA0825 28532 285600 Polydactyly, postaxial, type A10 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30982135 KIAA1549 22219 57670 Retinitis pigmentosa 86 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30120214 KIDINS220 29508 57498 Spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) AR N/A N/A Craniofacial; Endocrine; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27005418 KIF11 6388 3832 Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation AD N/A N/A Cardiovascular; Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15930898; 22653704; 22284827; 25115524 KIF14 19181 9928 Meckel syndrome 12; Microcephaly 20, primary, autosomal recessive AR N/A N/A Genitourinary; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24128419; 28892560; 29343805 KIF1A 888 547 NESCAV syndrome; Neuropathy, hereditary sensory, type IIC; Spastic paraplegia 30, autosomal dominant; Spastic paraplegia 30, autosomal recessive AD/AR N/A N/A Neurologic General Insensitivity to pain can result in injuries and infections Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21376300; 21487076; 21820098; 22258533 KIF1B 16636 23095 Neuroblastoma, susceptibility to; Pheochromocytoma AD Pediatric Allelic with Charcot-Marie-Tooth disease, axonal, type 2A1 (AD) Neurologic; Oncologic Oncologic Surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality 9409358; 11389829; 18334619; 24102379 KIF1C 6317 10749 Spastic ataxia 2, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24319291; 24482476 KIF21A 19349 55605 Fibrosis of extraocular muscles, congenital 1 AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10922204; 14595441; 15621877; 15621876; 15223798; 15671279; 15827546; 18332320; 19896199; 20301522; 21042561; 21805025 KIF22 6391 3835 Spondyloepimetaphyseal dysplasia with joint laxity, type 2 AD N/A N/A Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19277648; 22152677 KIF2A 6318 3796 Cortical dysplasia, complex, with other brain malformations 3 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23603762 KIF3B 6320 9371 Retinitis pigmentosa 89 AR Pediatric Cardiovascular; Gastrointestinal; Musculoskeletal; Ophthalmologic; Renal Cardiovascular; Gastrointestinal Among other features, the condition can include cardiac valvular anomalies, and early identificaiton may enable interventions; The condition can involve gastrointestinal anomalies, including leading to esophageal varices and other sequelae, and awareness may allow early identification and management 32386558 KIF4A 13339 24137 Mental retardation, X-linked 100 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24812067 KIF5A 6323 3798 Neonatal intractable myoclonus (NEIMY); Spastic paraplegia 10, autosomal dominant; Amyotrophic lateral sclerosis, susceptibility to, 25 AD N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10441583; 12355402; 15452312; 16489470; 16476820; 18245137; 18853458; 21107874; 21623771; 22788249; 25008398; 27414745; 27463701; 29342275; 29566793 KIF5C 6325 3800 Cortical dysplasia, complex, with other brain malformations 2 AD N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23033978; 23603762; 24812067 KIF7 30497 374654 Hydrolethalus syndrome 2; Acrocallosal syndrome; Joubert syndrome 12; Al-Gazali-Bakalinova syndrome AR/Digenic N/A N/A Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Renal; Ophthalmologic General The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Digenic inheritance (with CEP41) has been reported Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 457430; 7424976; 7102724; 7166318; 3802558; 3366141; 2658584; 2729349; 2729348; 2658583; 2308155; 2051463; 1659985; 1887856; 1499582; 8092201; 8723075; 11857542; 18618999; 20301500; 21633164; 21552264; 22246503; 22587682; 23142271 KIFBP 23419 26128 Goldberg-Shprintzen megacolon syndrome AR N/A N/A Gastrointestinal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7338549; 10874640; 15883926 KIRREL1 15734 55243 Nephrotic syndrome, type 23 AR Pediatric Renal Renal Individuals have been described with early-onset nephrotic syndrome, with remission achieved through medical management 31472902 KIRREL3 23204 84623 Mental retardation, autosomal dominant 4 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19012874 KISS1 6341 3814 Hypogonadotropic hypogonadism 13 with or without anosmia AR Pediatric Endocrine; Neurologic Endocrine In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 20301509; 22335740 KISS1R 4510 84634 Hypogonadotropic hypogonadism 8 with or without anosmia AR Pediatric Allelic with Precocious puberty, central 1 (AD) Endocrine; Neurologic Endocrine In Precocious puberty, treatment with gonadotropin-releasing hormone receptor analogs/LHRH agonists can be beneficial In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 11600530; 12788910; 12788881; 14573733; 18272894; 20301509 KIT 6342 3815 Gastrointestinal stromal tumor, familial; Mastocytosis, cutaneous AD Adult Allelic with Mastocytosis, cutaneous (AD); Piebaldism (AD) Dermatologic; Oncologic Oncologic For Gastrointestinal stromal tumor, surveillance may allow early diagnosis and treatment of gastrointestinal stromal tumors (including with tyrosine kinase inhibitors such as imatinib), which may improve outcomes 1717985; 9697690; 11073817; 11505412; 11174389; 15173254; 16143141; 16183119; 16185297; 17824795; 18724244; 18183595; 19847891; 21689725; 22083669 KITLG 6343 4254 Deafness, autosomal dominant 69 AD Pediatric Allelic with Hyperpigmentation with or without hypopigementation, familial progressive (AD); Skin/hair/eye pigmentation, variation in, 7 (AD) Audiologic/Otolaryngologic; Dermatologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 18083106; 17952075; 19375057; 26522471 KIZ 15865 55857 Retinitis pigmentosa 69 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24680887 KL 6344 9365 Tumoral calcinosis, hyperphosphatemic, familial, 3 AR Pediatric Dermatologic; Musculoskeletal; Renal Renal Phosphate reduction (eg, with dietary means and phosphate-binding agents) can be beneficial 4538804; 3659264; 2777854; 12541190; 17710231 KLC2 20716 64837 Spastic paraplegia, optic atrophy, and neuropathy AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26385635 KLF1 6345 10661 Anemia, dyserythropoietic congenital, type IV; Blood group, Lutheran inhibitor AD/BG Pediatric Allelic with Hereditary persistence of fetal hemoglobin (AD) (the described proband presented with mild hypochromic, microcytic red cell indices, but no other phenotypic abnormalities were reported) Hematologic Hematologic One individual has been described with multiple congenital anomalies in addition to hematologic perturbations Treatments (including regular RBC transfusions and splenectomy) may be beneficial; Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 1659863; 7680924; 7521883; 17319831; 18487511; 21055716; 20676099; 21531944; 21821711; 21273267; 22093801; 22102705 KLF11 11811 8462 Maturity-onset diabetes of the young, type VII AD N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15774581 KLHDC8B 28557 200942 Hodgkin lymphoma AD Pediatric Oncologic Oncologic One family with a gene disruption has been described Surveillance and/or awareness of cancer risk may allow early diagnosis, which could potentially be beneficial 19706467 KLHL10 18829 317719 Spermatogenic failure 11 AD N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17047026 KLHL15 29347 80311 Mental retardation, X-linked 103 XL N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24817631; 25644381 KLHL24 25947 54800 Epidermolysis bullosa simplex, generalized, with scarring and hair loss AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27798626; 27889062 KLHL3 6354 26249 Pseudohypoaldosteronism, type IID AD/AR Pediatric Renal Renal Treatment (eg, correction of physiologic abnormalities by thiazide diuretics) can be effective 22266938 KLHL40 30372 131377 Nemaline myopathy 8 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23746549 KLHL41 16905 10324 Nemaline myopathy 9 AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24268659 KLHL7 15646 55975 Perching syndrome (Crisponi/Cold-induced sweating syndrome 3) AR Pediatric Allelic with Retinitis pigmentosa 42 (AD) Musculoskeletal; Neurologic; Ophthalmologic Musculoskeletal In the neonatal/early childhood period, the condition can be lethal unless advanced care is instituted; Later, it has been described that cold-induced sweating was alleviated by medical treatment (eg, with clonidine) 1872134; 19520207; 20547956; 22084217; 27392078 KLK4 6365 9622 Amelogenesis imperfecta, type IIA1 AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15235027; 23355523 KLKB1 6371 3818 Prekallikrein deficiency AR N/A N/A Hematologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5845778; 5420590; 694428; 6568197; 3487556; 7717377; 6918357; 15461630; 19404525 KLLN 37212 100144748 Cowden syndrome 4 AD Adult Dermatologic; Oncologic Oncologic Germline hypermethylation and epigenetic inactivation of the KLLN promoter has been described in affected individuals Individuals have been reported with a high risk of breast and renal cancer, and surveillance may allow early diagnosis and management of neoplastic processes 21177507; 21956414 KMT2A 7132 4297 Wiedemann-Steiner syndrome AD N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22795537; 25810209 KMT2B 15840 9757 Dystonia 28, childhood-onset AD N/A N/A Neurologic General Surgical treatment (with deep brain stimulation) has been reported as effective Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27839873; 27992417 KMT2C 13726 58508 Kleefstra syndrome 2 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22726846; 29069077 KMT2D 7133 8085 Kabuki syndrome 1 AD Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dental; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal Cardiovascular; Renal Congenital heart defects, as well as arrhythmias, are frequent in affected individuals, and surveillance may allow early diagnosis and treatment; Individuals may have renal anomalies and/or vesicoureteral reflux, and screening for renal anomalies (eg, with ultrasound and functional testing) may allow measures to help monitor and preserve renal function 3067577; 8048822; 10190924; 11343317; 11665999; 12002156; 15108197; 15887282; 20711175; 21671394; 21607748; 21882399; 22126750; 23535010; 23913813 KMT2E 18541 55904 O'Donnell-Luria-Rodan syndrome AD N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31079897 KMT5B 24283 51111 Mental retardation, autosomal dominant, 51 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25363768; 28191889; 29276005 KNG1 6383 3827 High molecular weight kininogen deficiency AR N/A N/A Hematologic General Most individuals are asymptomatic, though one individual has been reported with cerebral artery thrombosis after moderate trauma Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1202089; 1174709; 16695963; 48123; 127805; 3728458; 1968772; 7901207; 12576314 KNL1 24054 57082 Microcephaly 4, primary, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10521316; 22983954 KPTN 6404 11133 Mental retardation, autosomal recessive 41 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24239382 KRAS 6407 3845 Noonan syndrome; Cardiofaciocutaneous syndrome AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic Cardiovascular; Hematologic; Oncologic Surveillance and treatment related to manifestations such as cardiac anomalies (which can include hypertrophic cardiomyopathy and arrhythmias) and short stature can be beneficial; An individual has been reported with a hematologic malignancy, and surveillance may be beneficial; Precautions related to bleeding risk can be beneficial 16474405; 16474404; 16474405; 17468812; 17056636; 18456719; 18042262; 19396835; 20301303; 20301365; 20358587; 20602484; 20876176; 21797849; 22211815; 22777296; 22510777; 23885229 KREMEN1 17550 83999 Ectodermal dysplasia 13, hair/tooth type AR N/A N/A Craniofacial; Dental; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27049303 KRIT1 1573 889 Cerebral cavernous malformations 1 AD Pediatric Cardiovascular; Dermatologic; Neurologic Cardiovascular; Neurologic; Pharmacogenomic Surveillance measures (eg, spinal cord MRI, annual brain gradient echo or susceptibility-weighted imaging) has been advocated; Agents that increase risk of hemorrhage should be avoided (eg, aspirin, NSAIDs, heparin, warfarin) 10508515; 10545614; 10814716; 11222804; 11310633; 11161805; 12404106; 11831930; 11914398; 15079030; 17562932; 17211633; 18060436; 18207546; 19099113; 19453802; 19454328; 20301470; 20306072; 20646827; 20689144; 20884211; 21029238; 22261708; 22510019; 22699465; 23584803; 23663874; 23806994; 23828392; 24007869; 24058906 KRT1 6412 3848 Keratosis palmoplantaris striata III; Ichthyosis, cyclic, with epidermolytic hyperkeratosis; Ichthyosis histrix, Curth-Macklin type; Palmoplantar keratoderma, epidermolytic; Palmoplantar keratoderma, nonepidermolytic; Epidermolytic hyperkeratosis AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14349943; 1381288; 1380725; 7682695; 7528239; 7512983; 10053007; 11286630; 11286616; 12406346; 11982762; 12648226; 16361731; 16417221; 16439967; 16487115; 16677804; 17255957; 18795921; 19470048; 21271994; 21496707; 22250628; 22834809 KRT10 6413 3858 Erythroderma, ichthyosiform, congenital reticular; Aaru disease; Ichthyosis, cyclic, with epidermolytic hyperkeratosis; Epidermolytic hyperkeratosis; Ichthyosis with confetti AD/AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1381287; 1380725; 7682695; 9036939; 19443303; 19474805; 19689541; 20302579; 20798280; 21271994; 21463361; 21929535; 22035476 KRT12 6414 3859 Meesmann corneal dystrophy 1 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9171831; 18661274; 20577595 KRT13 6415 3860 White sponge nevus 2 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7493031 KRT14 6416 3861 Epidermolysis bullosa simplex, autosomal recessive; Naegeli-Franceschetti-Jadassohn syndrome; Dermatopathia pigmentosa reticularis; Epidermolysis bullosa simplex, Koebner type; Epidermolysis bullosa simplex, Weber-Cockayne type; Epidermolysis bullosa simplex, Dowling-Meara type; Naegeli-Franceschetti-Jadassohn syndrome AD/AR N/A N/A Dental; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13149726; 939040; 1717157; 1303619; 7506606; 7526933; 7682883; 8496458; 7682695; 7525408; 7525407; 16098032; 16960809; 20180888; 20199538; 20301543; 21375516; 21593775; 21623745; 21818518; 21967011 KRT16 6423 3868 Palmoplantar keratoderma, nonepidermolytic, focal; Pachyonychia congenita 1 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7544664; 8595410; 10521820; 10839714; 11359398; 11886499; 20301457; 21160496; 21326300; 22098151; 22668561 KRT17 6427 3872 Steatocystoma multiplex; Pachyonychia congenita 2 AD N/A N/A Dental; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7529318; 7539673; 9008238; 11886499; 20301457; 22264670 KRT2 6439 3849 Ichthyosis bullosa of Siemens; Ichthyosis exfoliativa AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2138447; 2004005; 8077693; 7524919; 7521372; 9833038; 10084318; 10233323; 10620137; 11167982; 15949009 KRT25 30839 147183 Woolly hair, autosomal recessive 3 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26160856 KRT3 6440 3850 Corneal dystrophy, Meesmann, 2 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9171831 KRT4 6441 3851 White sponge nevus 1 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7493030; 10652003; 12828738 KRT5 6442 3852 Epidermolysis bullosa simplex with migratory circinate erythema; Epidermolysis bullosa simplex with mottled pigmentation; Dowling-Degos disease 1; Epidermolysis bullosa simplex, Koebner type; Epidermolysis bullosa simplex, Weber-Cockayne type; Epidermolysis bullosa simplex, Dowling-Meara type AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19991630; 13171638; 3188604; 1718160; 1372711; 7688477; 7686424; 7682695; 7520042; 7537780; 7534039; 8799157; 9129237; 10234505; 10730767; 11167681; 11407989; 12925204; 15324323; 16098032; 16465624; 20923750; 21144712 ; 21375516; 21569119; 22005030; 22583733; 22639907; 22747925 KRT6A 6443 3853 Pachyonychia congenita 3 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7545493; 11886499; 20301457; 22098151; 22264670; 22668561 KRT6B 6444 3854 Pachyonychia congenita 4 AD N/A N/A Dental; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9618173; 11886499; 20301457 KRT6C 20406 286887 Palmoplantar keratoderma, nonepidermolytic, focal or diffuse AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19609311; 21801157; 23662636 KRT71 28927 112802 Hypotrichosis 13 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22592156 KRT74 28929 121391 Ectodermal dysplasia 7, hair/nail type; Hypotrichosis 3; Woolly hair, autosomal dominant AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20346438; 20409997; 21188418; 24714551 KRT75 24431 9119 Pseudofolliculitis barbae AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15086549 KRT81 6458 3887 Monilethrix AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9665406; 15744029; 22628999 KRT83 6460 3889 Monilethrix; Erythrokeratodermia variabilis et progressiva 5 AD/AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15744029; 27965375 KRT85 6462 3891 Ectodermal dysplasia 4, hair-nail type AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16525032; 19865094 KRT86 6463 3892 Monilethrix AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9241275; 9665406; 10878478; 15744029; 19400537; 22568869; 22670615 KRT9 6447 3857 Palmoplantar keratoderma, epidermolytic; Knuckle pads AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7528239; 7512862; 7511021; 9856842; 12192490; 12838553; 17074468; 19106041 KY 26576 339855 Myopathy, myofibrillar, 7 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27484770; 27485408 KYNU 6469 8942 Hydroxykynureninuria; Vertebral, cardiac, renal, and limb defects syndrome 2 AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Renal General Vertebral, cardiac, renal, and limb defects syndrome 2 can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17334708; 28792876 L1CAM 6470 3897 Hydrocephalus due to congenital stenosis of aqueduct of Sylvius; Mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) syndrome; CRASH syndrome; Corpus callosum, partial agenesis of; Spastic paraplegia-1 XL N/A N/A Gastrointestinal; Musculoskeletal; Neurologic General Individuals may be at risk for findings including Hirschsprung disease as well as hydrocephalus Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4855169; 7070456; 6702900; 2737668; 2277384; 1870106; 1303258; 7920659; 8062435; 7920660; 8556302; 7562969; 9279760; 15368500; 16650080; 21271669; 21644943; 21839187; 21961551; 22222883; 22344793; 22354677 L2HGDH 20499 79944 L-2-hydroxyglutaric aciduria AR Pediatric Biochemical; Neurologic; Oncologic Biochemical; Oncologic A low lysine diet has been reported as resulting in clinical and biochemical improvement; An increased risk of cerebral neoplasms has been reported, and awareness may lead to early detection and treatment 6787330; 1642474; 7609438; 7609437; 9860123; 10399870; 15548604; 15385440; 15824270; 18931888; 21937992; 22241392; 22353300; 22459673 LACC1 26789 144811 Juvenile arthritis AR Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic Individuals have been described as benefiting from specific medications (with non-efficacy of other medications), and knowledge may help with medication selection; The condition may involve increased risk of malignancy, and awareness may allow prompt diagnosis and management; BMT has been described 25220867; 27881174; 29717096; 30872671 LAGE3 26058 8270 Galloway-Mowat syndrome 2, X-linked XL N/A N/A Craniofacial; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28805828 LAMA1 6481 284217 Poretti-Boltshauser syndrome AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25105227 LAMA2 6482 3908 Schizophrenia; Muscular dystrophy, congenital merosin-deficient, 1A; Muscular dystrophy, limb-girdle, autosomal recessive 23 AD/AR N/A N/A Musculoskeletal; Neurologic General Clinically significant cardiomyopathy has not been described In Muscular dystrophy, congenital merosin-deficient, 1A, Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; In Schizophrenia, the evidence or clinical applicability is unclear 7550355; 8887959; 8729391; 12552556; 16216942; 18700894; 20627570; 21953594; 22166137; 22675738; 23042115; 24611677; 25663498; 30055037 LAMA3 6483 3909 Laryngoonychocutaneous syndrome; Epidermolysis bullosa, junctional, Herlitz type; Epidermolysis bullosa, generalized atrophic benign AR N/A N/A Audiologic/Otolaryngologic; Dental; Dermatologic General The condition can include life-threatening respiratory obstruction Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1342856; 8185366; 7633458; 8530087; 8618022; 8586427; 11810295; 12915477; 20301304; 20881434; 22434185; 22963541 LAMA4 6484 3910 Cardiomyopathy, dilated, 1JJ AD Pediatric Cardiovascular Cardiovascular Although clinical effects have been described in older individuals, in at least one individual, the onset of cardiac pathology was such that surveillance may be indicated prior to adulthood Individuals may have cardiovascular manifestations including dilated cardiomyopathy, and surveillance (eg, with echocardiogram) may allow detection and early medical treatment, which may be beneficial to help decrease morbidity; Heart transplantation was described as indicated in one individual 17646580 LAMB1 6486 3912 Lissencephaly 5 AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23472759; 25925986 LAMB2 6487 3913 Pierson syndrome; Nephrotic syndrome, type 5, with or without ocular abnormalities AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic; Renal General Chronic renal dialysis can extend life of affected individuals Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14136829; 15367484; 16912710; 17256789; 19251977; 21236492 LAMB3 6490 3914 Epidermolysis bullosa, junctional, Herlitz type AR Pediatric Allelic with Amelogenesis imperfecta, type IA (AD); Epidermolysis bullosa, junctional, non-Herlitz type (AR) Dental; Dermatologic Dermatologic Epidermolysis bullosa, junctional, Herlitz type, involves a severe and sometimes fatal blistering skin disease, and treatment with autologous transgenic keratinocyte cultures has been described as beneficial 7706760; 7774918; 9205497; 9242513; 11023379; 15538630; 16473856; 17476356; 20301304; 19369679; 20301304; 21801158; 23632796; 23958762; 29144448 LAMC2 6493 3918 Epidermolysis bullosa, junctional, Herlitz type; Epidermolysis bullosa, junctional, non-Herlitz type AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8012393; 11810295; 16473856; 21198797; 21801158 LAMC3 6494 10319 Cortical malformations, occipital AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21572413 LAMP2 6501 3920 Danon disease XL Pediatric Biochemical; Cardiovascular; Musculoskeletal; Neurologic Cardiovascular Males typically display mental retardation and other recognizable features, but females may be affected with cardiomyopathy and arrhthymias Surveillance (eg, with EKG and electrocardiogram) and medical management can help decrease morbidity related to cardiomyopathy and arrhythmias; Heart transplant has been suggested to be the only truly effective treatment 6450334; 3806120; 3057987; 8504498; 7919972; 10972294; 12084876; 15253947; 15673802; 15889279; 15792868; 15907287; 17899313; 19318653; 21161685; 21816855; 22074992; 22365987; 22541782; 22750798 LAMTOR2 29796 28956 Immunodeficiency due to defect in MAPBP-interacting protein AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Musculoskeletal Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial (severe congenital neutropenia has been reported as responding to G-CSF) 17195838 LARGE1 6511 9215 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6 AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12966029; 17878207; 17436019; 19067344; 19299310; 21248746 LARP7 24912 51574 Alazami syndrome AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22865833; 30006060 LARS1 6512 51520 Infantile liver failure syndrome 1 AR N/A N/A Gastrointestinal; Hematologic; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22607940 LARS2 17095 23395 Perrault syndrome 4 AR Pediatric Allelic with Hydrops, lactic acidosis, and sideroblastic anemia (AR) Audiologic/Otolaryngologic; Endocrine; Genitourinary; Hematologic; Obstetric; Pulmonary Audiologic/Otolaryngologic; Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Obstetric Genetic knowledge may allow fertility preservation such as by storing eggs in woman with premature ovarian failure 23541342; 26537577; 32442335 LAS1L 25726 81887 Wilson-Turner X-linked mental retardation syndrome XL N/A N/A Craniofacial; Endocrine; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25644381 LAT 18874 27040 Immunodeficiency 52 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT has been described 27242165; 27522155 LBR 6518 3930 Reynolds syndrome; Pelger-Huet anomaly; Pelger-Huet anomaly with mild skeletal anomalies; Greenberg skeletal dysplasia AD/AR N/A N/A Craniofacial; Hematologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5553949; 3475111; 12118250; 14684694; 12618959; 20522425; 22338047 LCA5 31923 167691 Leber congenital amaurosis 5 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10631161; 12642313; 17546029; 18334959; 20301475; 21850168 LCAT 6522 3931 Lecithin:cholesterol acyltransferase deficiency (Norum disease); Fish-eye disease AR Pediatric Biochemical; Cardiovascular; Hematologic; Ophthalmologic; Renal Cardiovascular; Renal Dietary measures (eg, reducing fat intake) may be beneficial in controlling LDL and decreasing sequelae; In LCAT deficiency, medical treatment related to renal disease (eg, with ACE inhibitors) may preserve renal function, though renal transplant may be required 5704704; 408950; 7156322; 7148518; 6624548; 6695915; 3661502; 1898657; 2370048; 2052566; 9180249; 9884427; 18042612; 21901787; 22108153; 22189200; 22701329; 23043194; 23391322; 23412821; 23522979 LCK 6524 3932 Immunodeficiency 22 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 9664084; 11351273; 22985903 LCT 6530 3938 Lactase deficiency, congenital AR Pediatric Gastrointestinal Gastrointestinal Upstream/noncoding variants may also result in adult-onset lactose intolerance Breast-feeding or lactose-containing formulas leads to severe osmotic diarrhea, which can be treated effectively with lactose-free diet 5419986; 6847226; 9758622; 11788828; 16400612; 17345962; 19161632; 19432082; 22688420; 23445879 LDB3 15710 11155 Cardiomyopathy, dilated 1C, with or without ventricular noncompaction; Myopathy, myofibrillar 4 AD Pediatric Cardiovascular; Musculoskeletal Cardiovascular LVNC may present early, while other cardiac manifestations may not present until much later Individuals may have cardiovascular manifestations including dilated cardiomyopathy, and surveillance (eg, with echocardiogram) may allow detection and early medical treatment, which may be beneficial to help decrease morbidity; In myofibrillar myopathy, individuals typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD); Cardiac transplantation may be necessary in individuals with severe forms of cardiomyopathy 14662268; 14660611; 15668942; 16427346; 17337483; 20627570; 20809097 LDHA 6535 3939 Glycogen storage disease XI AR Pediatric Biochemical; Dermatologic; Musculoskeletal; Renal Biochemical; Musculoskeletal; Renal Individuals can have exertional myoglobinuria, and renal failure has been reported, such that precautions (eg, involving exercise) may be beneficial 7449146; 3092644; 3383424; 2334430; 1959923; 1999544 LDHB 6541 3945 Lactate dehydrogenase B deficiency AR N/A N/A Biochemical General The clinical significance is unclear 5119336; 6383647; 2334429; 70259; 10509905; 11509017 LDHD 19708 197257 D-lactic aciduria AR Adult Biochemical; Musculoskeletal; Neurologic; Renal Renal The condition can manifest with gouty arthropathy, and medical (eg, with colchicine and allopurinol) and dietary management (eg, related to meat consumption) has been reported as beneficial 30931947; 31638601 LDLR 6547 3949 Hypercholesterolemia, familial 1 AD/AR Pediatric Cardiovascular Cardiovascular Dietary and medical measures (eg, with statins) to lower cholesterol levels may be beneficial, with evidence that early diagnosis and management improves outcomes; In severe instances, therapy may include plasma apharesis, and gene therapy has been described; In Hypercholesterolemia, familial, 1, medical management (with inclisiran, a small interfering RNA), has shown evidence of benefit related to parameters such as LDL levels 3020025; 3155573; 3924410; 3012527; 3549308; 3815525; 3818645; 3343347; 2837085; 3263645; 2563635; 2569482; 2544509; 2088165; 1978682; 1999337; 1863993; 1609792; 1734722; 8098448; 8054972; 9016531; 9645910; 10422803; 11246453; 10631147; 10882754; 11453971; 11600564; 11298688; 15657370; 17335829; 17215532; 18400033; 18354102; 20703241; 20686565; 21722902; 21872251; 21925044; 22244043; 22698793; 22881376; 22893714; 23054246; 32187462; 32197277 LDLRAP1 18640 26119 Hypercholesterolemia, familial, 4 AR Pediatric Cardiovascular; Dermatologic Cardiovascular Interventions to maintain lipid profiles at a more desirable level can decrease morbidity/mortality, such as relates to CAD 11326085; 15599766; 21872251 LEFTY2 3122 7044 Left-right axis malformations AD N/A N/A Cardiovascular; Pulmonary General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10053005 LEMD2 21244 221496 Marbach-Rustad progeroid syndrome; Cataract 46, juvenile onset, with or without arrhthythmic cardiomyopathy AD/AR Pediatric Cardiovascular; Dental; Endocrine; Neurologic; Ophthalmologic Cardiovascular; Endocrine Individuals with Marbach-Rustad progeroid syndrome have been described with cardiac manifestations, and awareness may allow early diagnosis and management; Individuals with Marbach-Rustad progeroid syndrome have been described as receiving treatment with growth hormone therapy; In Cataract 46, juvenile onset, with or without arrhthythmic cardiomyopathy, individuals have been described with cardiovascular manifestations including arrhythmic cardiomyopathy and sudden cardiac death, and awareness may allow early diagnosis and management; Heart transplant has been described 23863954; 26788539; 30905398; 31061923 LEMD3 28887 23592 Buschke-Ollendorff syndrome; Osteopoikilosis AD N/A N/A Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12749062; 15489854; 17223882; 17087626; 19438932; 20618940; 20732851; 21985280 LEP 6553 3952 Leptin deficiency or dysfunction AR Pediatric Endocrine Endocrine Heterozygotes may display milder forms of disease Severely affected individuals may benefit from treatment with leptin 9202122; 9745435; 9500540; 10486419; 11281277; 11689931; 15070752; 17986612; 17206122; 19427251; 20382689; 22463805 LEPR 6554 3953 Leptin receptor deficiency AR Pediatric Allergy/Immunology/Infectious; Endocrine Allergy/Immunology/Infectious; Endocrine Standard treatments for obesity, such as gastric surgery, have been described as beneficial In addition to endocrine manifestations, individuals may be susceptible to infections (eg, respiratory infections), which, coupled with other manifestations (eg, severe obesity) can have severe sequelae such that prophylaxis and rapid treatment may be beneficial 8666155; 9537324; 17229951; 21306929; 23275530; 23616257 LFNG 6560 3955 Spondylocostal dysostosis 3, autosomal recessive AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16385447; 20301771 LGI1 6572 9211 Epilepsy, familial temporal lobe, 1 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8773604; 11906506; 12205652; 11810107; 15079010; 15079011; 17562837; 19064878; 20301709; 21444903; 21504429; 22496201 LGI4 18712 163175 Arthrogryposis multiplex congenita, neurogenic, with myelin defect AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28318499 LHB 6584 3972 Hypogonadotropic hypogonadism 23 with or without anosmia AR Pediatric Endocrine Endocrine Homozygous/compound heterozygous males may not undergo spontaneous puberty, and treatment (eg, with HCG) can be beneficial; Females may be affected with infertility and oligo-amenorrhea, and medical treatment (eg, with HCG) may be beneficial 429481; 1727547; 7904610; 7714098; 9457942; 15602022; 19129711; 19890128; 22723313 LHCGR 6585 3973 Leydig cell hypoplasia type I; Leydig cell hypoplasia type II; Luteinizing hormone resistance, female; Precocious puberty, male AR Pediatric Endocrine; Genitourinary; Oncologic Endocrine; Genitourinary; Oncologic Both germline and somatic variants have been described In mild forms of LCH, the disorder may not be clinically recognized early, and exogenous testosterone can result in normal virilization; In Precocious puberty, male, medical therapy (eg, with combined spironolactone and testolactone) has been reported as beneficial; Surveillance for related neoplasms (eg, testicular neoplasms) may allow prompt diagnosis and treatment 184390; 6792847; 3557461; 3812586; 2492636; 7692306; 7719343; 7581384; 8559204; 8923827; 9703386; 9817592; 10580072; 10714363; 10704433; 11391350; 11857565; 19129711; 21060208; 21683950; 21720050; 22369774; 22931948 LHFPL5 21253 222662 Deafness, autosomal recessive 67 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 16752389; 16459341 LHX3 6595 8022 Pituitary hormone deficiency, combined, 3 AR Pediatric Audiologic/Otolaryngologic; Endocrine; Musculoskeletal; Neurologic Audiologic/Otolaryngologic; Endocrine Medical treatment of endocrine deficiencies, which can include congenital hypothyroidism and ACTH deficiency, can be beneficial; Awareness of hearing impairment can allow prompt interventions related to speech and language development 10835633; 16394081; 17327381; 18407919; 22238406; 22286346 LHX4 21734 89884 Pituitary hormone deficiency, combined, 4 AD Pediatric Endocrine; Musculoskeletal; Neurologic; Pulmonary Endocrine Individuals can prevent neonatally with severe manifestations due to endocrine anomalies such as hypoglycemia; Respiratory distress has also been described at presentation; Other corrections of endocrine anomalies, such as growth hormone deficiency treatment, can be beneficial 11567216; 17527005; 18073311; 19856252; 20534763; 22232309; 23029363; 23761422 LIAS 16429 11019 Pyruvate dehydrogensae lipoic acid synthetase deficiency AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22152680; 24334290 LIFR 6597 3977 Stuve-Wiedemann syndrome AR N/A N/A Musculoskeletal; Neurologic General Individuals can have temperature control anomalies and other manifestations of dysautonomia Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4105362; 8728692; 9382147; 9674905; 9674906; 12514358; 14740318; 18546280; 19371797; 20447141 LIG4 6601 3981 LIG4 syndrome; Severe combined immunodeficiency with sensitivity to ionizing radiation AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Oncologic Allergy/Immunology/Infectious; Hematologic; Oncologic Antiinfectious prophylaxis and early and aggressive treatment of infections and hematologic anomalies may be beneficial; Oncologic disorders have also been described, and surveillance may allow prompt treatment 11779494; 15333585; 16088910; 16357942 LIM2 6610 3982 Cataract 19 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11917274 LIMA1 24636 51474 Low density lipoprotein cholesterol level quantitative trait locus AD N/A N/A Gastrointestinal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29880681 LIMS2 16084 55679 Muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue AD Adult Cardiovascular; Craniofacial; Musculoskeletal Cardiovascular The condition can include dilated cardiomyopathy, and knowledge may allow early diagnosis and medical management 25589244 LINGO1 21205 84894 Mental retardation, autosomal recessive 64 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28837161 LINS1 30922 55180 Mental retardation, autosomal recessive 27 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21937992; 23773660 LIPA 6617 3988 Cholesterol ester storage disease; Wolman disease AR Pediatric Biochemical; Cardiovascular; Gastrointestinal Biochemical; Cardiovascular Enzyme replacement therapy has been shown to be beneficial in terms of clinical parameters including liver function testing, LDL levels, and hepatic fat content; Treatment with HMG-CoA reductase inhibitors may be effective for management of atherosclerotic risk in milder forms of the condition; Enzyme replacement therapy (eg, with sebelipase alfa) has been described; HSCT has been described 14008104; 5642714; 5477680; 859064; 2347551; 1528002; 8254026; 8146180; 8617513; 18174560; 18776925; 19214773; 19308038; 21291321; 21963785; 22227072; 23007684; 23035117; 23348766; 23999269; 24072694; 24122380; 26352813 LIPC 6619 3990 Hepatic lipase deficiency AR Pediatric Cardiovascular Cardiovascular Surveillance and treatment for cholesterol and cardiovascular perturbations may decrease morbidity and mortality 1883393; 1671786; 12777476; 19428034 LIPE 6621 3991 Lipodystrophy, familial partial, type 6 AR Pediatric Cardiovascular; Endocrine Cardiovascular Heterozygous individuals may also demonstrate findings including dyslipidemia and insulin resistance Among other manifestations, individuals have been described with dyslipidemia, and awareness may allow surveillance and early management 24848981; 27862896 LIPH 18483 200879 Hypotrichosis 7 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17095700; 17333281; 18445047; 19365138; 19892526; 21426374; 23590372 LIPI 18821 149998 Hypertriglyceridemia, familial AD Pediatric Cardiovascular Cardiovascular Surveillance and treatment for cholesterol and cardiovascular perturbations may decrease morbidity and mortality 12719377 LIPN 23452 643418 Ichthyosis, congenital, autosomal recessive 8 AR N/A N/A Dermatologic General There are suggestions that treatment may be tailored by more precise (ie, genetic) diagnosis Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12780701; 21439540 LIPT1 29569 51601 Lipoyltransferase 1 deficiency AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24256811; 24341803 LIPT2 37216 387787 Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28757203 LITAF 16841 9516 Charcot-Marie-Tooth disease, type 1C AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11713717; 12525712; 19541485; 20301384; 23319192 LMAN1 6631 3998 Combined factor V and VIII deficiency AR Pediatric Hematologic Hematologic Individuals can suffer from bleeding diatheses of varying severity, and preventive measures related to bleeding episodes can be beneficial 13575936; 14452289; 4638375; 564138; 9045860; 9546392; 16304051; 18391077; 18685427; 19787799; 23006835 LMAN2L 19263 81562 Mental retardation, autosomal recessive, 52 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26566883 LMBR1 13243 64327 Acheiropody; Syndactyly, type IV; Laurin-Sandrow syndrome; Triphalangeal thumb, type I; Polydactyly, preaxial type II; Triphalangeal thumb-polysyndactyly syndrome; Tibial aplasia/hypoplasia; Hypoplastic or aplastic tibia with polydactyly AD/AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal General Conditions may be due to variants in a SHH-regulatory element within an LMBR1 intron Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5808544; 1132167; 1155460; 1163539; 6660253; 10937618; 10780921; 11090342; 12837695; 16059937; 17152067; 17476456; 17300748; 18463159; 18178630; 18417549; 19291772; 20068592; 20569257; 22495965; 24456159; 24965254 LMBRD1 23038 55788 Methylmalonic aciduria and homocystinuria, cblF type AR Pediatric Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Dermatologic; Hematologic; Neurologic Biochemical While no treatment is completely effective, specific dietary (eg, high-calorie, low protein diet and avoidance of fasting, with measures taken to avoid/treat decompensation) and other medical measures (eg, cofactor therapy with hydroxycobalamin) may be beneficial to treat and prevent sequelae in the acute and chronic states 4001945; 3725502; 20301503; 19136951; 20127417; 21910240; 21303734; 22065268; 20446115 LMF1 14154 64788 Combined lipase deficiency AR Pediatric Cardiovascular; Endocrine; Gastrointestinal Cardiovascular; Endocrine; Gastrointestinal Individuals may present with severe hypertryglceridemia, with findings including gastrointestinal manifestations (abdominal pain, emesis, recurrent pancreatitis, hepatosplenomegaly), as well as eruptive xanthomata and lipemia retinalis, and dietary measures (fat restriction) and medical treatment (eg, gemfibrozil, omega-3 fatty acid supplementation) can be beneficial; Individuals may also manifest with diabetes mellitus, which can benefit from standard treatment (and which may also help with other manifestations) 17994020; 19820022 LMNA 6636 4000 Cardiomyopathy, dilated, 1A; Heart-hand syndrome, Slovenian type; Emery-Dreiffus muscular dystrophy 2, autosomal dominant; Emery-Dreiffus muscular dystrophy 3, autosomal recessive; Muscular dystrophy, congenital, LMNA-related; Muscular dystrophy, limb-girdle, type 1B; Cardiomyopathy, dilated, with hypergonadotropic hypogonadism (Malouf syndrome); Lipodystrophy, familial partial, 2 (Dunnigan type) AD/AR Pediatric Allelic with Hutchinson-Guilford Progeria (AD); Restrictive dermopathy, lethal (AD); Charcot-Marie-Tooth disease, axonal, type 2B1 (AR); Mandibuloacral dysplasia with type A lipodystrophy (AR) Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Hematologic; Musculoskeletal; Neurologic Cardiovascular Some allelic conditions are clinically recognizable, and in these, it is not clear if early (genetic) diagnosis would be additionally beneficial Some LMNA-associated conditions can include cardiac anomalies, including arrhythmias and cardiomyopathy that can precede other obvious clinical signs/symptoms, and medical (eg, ICD placement) management prior to severe sequelae may be beneficial 4362786; 1205025; 3519971; 2957478; 9920078; 10080180; 10580070; 10662742; 10587585; 10814726; 10843151; 10814726; 10655060; 10739751; 11231979; 11799477; 12075506; 12768443; 12629077; 12673789; 12927431; 12702809; 12714972; 12920062; 14627682; 12788894; 12628721; 15028826; 15148145; 15317753; 15286156; 15961312; 15622532; 15668447; 16407522; 16278265; 17136397; 17250669; 17848409; 17469202; 17150192; 17325275; 17377071; 18256394; 18551513; 18364375; 18348272; 18805829; 19084400; 19283854; 21483645; 20301582 ; 20301717; 20301609; 20301300; 20301462; 22199124; 22177269; 22224630; 22240398; 22274718; 22431096; 22491857; 22700598; 22806367; 25649378 LMNB1 6637 4001 Leukodystrophy, demyelinating, adult-onset, autosomal dominant; Microcephaly 26, primary, autosomal dominant AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16951681; 19151023; 21225301; 21909802; 23243074; 23649844; 32910914; 33033404 LMNB2 6638 84823 Liopdystrophy, partial, acquired; Microcephaly 27, primary, autosomal dominant; Epilepsy, progressive myoclonic, 9 AD/AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16826530; 22768673; 25954030; 33033404 LMOD1 6647 25802 Megacystis-microcolon-intestinal hypoperistalsis syndrome 3 AR N/A N/A Genitourinary; Gastrointestinal; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28292896 LMOD3 6649 56203 Nemaline myopathy 10 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25250574; 30291184 LMX1A 6653 4009 Deafness, autosomal dominant 7 AD Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 29754270 LMX1B 6654 4010 Nail-patella syndrome; Focal segmental glomerulosclerosis 10 AD Pediatric Dermatologic; Musculoskeletal; Ophthalmologic; Renal Ophthalmologic; Pharmacogenomic; Renal Onset may typically be during adulthood, though surveillance earlier may be warranted given reports of affected individuals in the 3rd decade In Nail-patella syndrome, individuals may have open-angle glaucoma, and surveillance and appropriate treatment may be beneficial; Agents that may contribute to glaucoma (as well as NSAIDs as relates to renal function) should be avoided; Medical treatment (eg, ACE inhibitors) may be beneficial in terms of affecting the progression of renal disease; Renal transplantation has been described; In Focal segmental glomerulosclerosis, recognition of disease may allow early management, and renal transplant has been described 9590287; 9618165; 15928687; 17515884; 18414507; 20301311; 21850167; 23687361; 32356190; 32791958 LNPK 21610 80856 Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30032983 LONP1 9479 9361 Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies (CODAS) syndrome AR N/A N/A Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25574826 LORICRIN 6663 4014 Vohwinkel syndrome, variant form AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8673107; 9326323; 9326398; 16403113 LOX 6664 4015 Aortic aneurysm, familial thoracic 10 AD Pediatric Cardiovascular; Musculoskeletal Cardiovascular Individuals can manifest with thoracic aortic aneurysm with or without dissection as well as other features, and awareness may allow preventive measures and early diagnosis and management 26838787; 27432961 LOXHD1 26521 125336 Deafness, autosomal recessive 77 AR N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19732867; 23226338 LPA 6667 4018 Lipoprotein A deficiency, congenital AR N/A N/A General General The clinical relevance of the condition is unclear 7726859; 10484779; 15523644; 16840570; 16267501; 20032323 LPAR6 15520 10161 Hypotrichosis 8 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18461368; 18297070; 18297072; 21070332; 21426374 LPIN1 13345 23175 Myoglobinuria, acute, recurrent, autosomal recessive AR Pediatric Musculoskeletal; Renal Musculoskeletal; Pharmacogenomic; Renal Attacks are typically trigerred by illnesses rather than exercise, and avoidance of fasting and prompt treatment of febrile illness may prevent severe sequelae such as renal failure; Anesthesia precautions can be beneficial in order to decrease the risk of malignant hyperthermia 6851679; 1544519; 18817903 LPIN2 14450 9663 Majeed syndrome AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Hematologic Allergy/Immunology/Infectious; Hematologic Individuals may manifest with Chronic recurrent multifocal osteomyelitis (CRMO), for which treatment with NSAIDs/corticosteroids may be beneficial; Individuals may require surveillance and blood transfusion treatment for anemia 11381255; 17011878; 17330256; 18055821; 20301735; 22559933; 22570351 LPL 6677 4023 Hyperlipidemia, familial combined, 3; Lipoprotein lipase deficiency AD/AR Pediatric Cardiovascular; Gastrointestinal; Hematologic Cardiovascular; Gastrointestinal; Pharmacogenomic Heterozygous variants can contribute to Familial combined hyperlipidemia (LPL deficiency is an autosomal recessive disorder) Patients with Hyperlipidemia, familial combinedL are at increased risk of cardiovascular disease, as well as other comorbid conditions, and awareness may allow early medical and lifestyle management to prevent sequelae; In LPL deficiency, treatment centers on medical (eg, inhibitors of APOC3 mRNA have been reported as beneficial related to lower triglyceride measurements) and nutrition therapy (eg, reducing fat intake, alcohol abstinence, as well as antioxidant therapy related to risks of sequelae) aimed to maintain plasma triglyceride concentration less than 1000 mg/dL; In LPL deficiency, gene therapy (Alipogene tiparvovec) is clinically available; Treatment of acute pancreatitis involves fasting with low-calorie infusion; Medical treatment (eg, with fibrates) may be beneficial in adults with LPL deficiency; Certain medications that can affect triglyceride levels should be avoided, and sequelae such as pancreatitis may be precipitated by OCPs 13483896; 13712364; 3630977; 4719678; 6638056; 6645961; 2648155; 2536938; 2110364; 2294743; 1969408; 2121025; 1975597; 2394828; 2010533; 1702428; 1907278; 1752947; 1674945; 2038366; 1530621; 1562620; 1400331; 1598907; 1511985; 1639392; 1512512; 1731801; 1737848; 8096693; 8486765; 8325986; 7906986; 8541837; 7753827; 8755931; 8778602; 9401010; 9738727; 10517255; 10199753; 11134145; 11334614; 15928243; 16174715; 15840743; 16552344; 17032721; 19295657; 20301485; 21159338; 22129523; 22239554; 22438229; 22717743; 23527320; 24142281; 25470695; 30307446 LRAT 6685 9227 Leber congenital amaurosis 14; Retinitis pigmentosa, juvenile; Retinal-dystrophy, early-onset severe; Retinitis punctata albescens AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11381255; 17011878; 18055821; 22559933; 22570351 LRBA 1742 987 Common variable immunodeficiency 8, with autoimmunity AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Endocrine; Hematologic Allergy/Immunology/Infectious; Hematologic The condition may include infectious and autoimmune manifestations Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; The condition may include autoimmune phenomena including hematologic manifestations (eg, thrombocytopenia, anemia), and surveillance and early diagnosis and treatment may be beneficial; Automimune manifestations (interstitial lung disease, enteritis) have been reported as responding to a CTLA4-immunoglobin fusion drug 22608502; 22981790; 25468195; 26206937 LRIG2 20889 9860 Urofacial syndrome 2 AR Pediatric Craniofacial; Renal Renal Wilms tumor has been reported in one individual Individuals have been described with manifestations including low-capacity, overactive bladder, vesicoureteral reflux, hydronephrosis, urosepsis, and renal impairment, though treatment attempts (eg, with intermittent catheterization, antimuscarinic agents, and surgical bladder augmentation) were not reported as slowing slow renal failure, and dialysis was required in at least one individual; Early recognition may allow management aimed at preserving renal function 23313374 LRIT3 24783 345193 Night blindness, congenital stationary, type 1F AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23246293 LRMDA 23405 83938 Albinism, oculocutaneous, type VII AR N/A N/A Dermatologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23395477 LRP1 6692 4035 Schizophrenia; Keratosis pilaris atrophicans AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21743468; 26142438 LRP12 31708 29967 Oculopharyngodistal myopathy 1 AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31332380 LRP2 6694 4036 Donnai-Barrow syndrome; Faciooculoacousticorenal syndrome AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic; Renal Audiologic/Otolaryngologic; General The condition can involve multiple congenital anomalies Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 8266995; 9475100; 12923867; 17632512; 18553518; 20301732 LRP4 6696 4038 Cenani-Lenz syndactyly syndrome; Myasthenic syndrome, congenital 17; Sclerosteosis 2 AD/AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Renal General Cenani-Lenz syndactyly syndrome can involve multiple congenital anomalies; In Myasthenic syndrome, congenital, treatment with cholinesterase inhibitor was not effective Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7891385; 9182770; 10756427; 11260233; 11385236; 14577675; 12868467; 18978656; 20381006; 21471202; 24234652 LRP5 6697 4041 van Buchem disease, type 2; Osteopetrosis, autosomal dominant 1; Polycystic liver disease 4 with or without kidney cysts; Endosteal hyperostosis, autosomal dominant; Exudative vitreoretinopathy 4; Osteoporosis-pseudoglioma syndrome AD/AR/Digenic N/A N/A Gastrointestinal; Musculoskeletal; Ophthalmologic; Renal General Digenic inheritance (with FZD4) has been reported in Exudative vitreoretinopathy Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8832721; 9056564; 9831343; 10434540; 11719191; 12015390; 11741193; 12054167; 12579474; 15346351; 15024691; 15981244; 20301326; 21407258; 21600326; 22456437; 22487062; 23077402; 25920554 LRP6 6698 4040 Coronary artery disease, autosomal dominant 2 AD Pediatric Allelic with Tooth agenesis, selective, 7 (AD) Cardiovascular; Dental Cardiovascular While severe manifestations may occur later in life, surveillance and preventive measures may be beneficial prior to adulthood Preventive measures related to control of contributing factors associated with coronary artery disease may be beneficial to reduce morbidity and mortality 17332414; 23703864; 26387593 LRPAP1 6701 4043 Myopia 23, autosomal recessive AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23830514; 25525168 LRPPRC 15714 10128 Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) AR N/A N/A Biochemical; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8392290; 8392291; 12529507; 21266382 LRRC32 4161 2615 Cleft palate, proliferative retinopathy, and developmental delay AR N/A N/A Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30976112 LRRC56 25430 115399 Ciliary dyskinesia, primary 39 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial; Individuals may require surgery or other interventions related to congenital cardiac malformations 30388400 LRRC8A 19027 56262 Agammaglobulinemia 5 AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Only one individual (with a translocation affecting LRRC8A) has been described; This individual also demonstrated dysmorphic facies in addition to agammaglobulinemia Congenital agammaglobulinemia has been described, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 14660746 LRRK2 18618 120892 Parkinson disease 8, autosomal dominant AD Adult Neurologic Neurologic Response to levodopa has been documented 15541309; 16437584; 16437559; 19458969 LRSAM1 25135 90678 Charcot-Marie-Tooth disease, axonal, type 2P AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20865121; 22012984; 22781092 LRTOMT 25033 220074 Deafness, autosomal recessive 63 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 17166180; 17066295; 18953341; 18794526 LSS 6708 4047 Cataract 44; Alopecia-mental retardation syndrome 4; Hypotrichosis 14 AR N/A N/A Dermatologic; Genitourinary; Neurologic; Ophthalmologic General Research investigations suggest that lanosterol may be beneficial for prevention and treatment of Cataract 44 Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26200341; 30401459; 30723320 LTBP2 6715 4053 Glaucoma 3, primary congenital, D; Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma; Weill-Marchesani syndrome 3 AR Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic Cardiovascular; Ophthalmologic; Pharmacogenomic Surveillance, early diagnosis, and treatment of manifestations such as ectopia lentis and glaucoma with surgical interventions (with the use of pre and postoperative agents to control intraocular pressure), or, if surgery is not effective, drainage implants or cyclodestruction, may be effective to decrease morbidity and mortality related to vision loss; Individuals with cardiovascular manifestations including pulmonary and aortic stenosis have been described, and awareness may allow early diagnosis and treatment; Agents that may contribute to glaucoma, as well as alpha-2-agonists, should be avoided 18776954; 19361779; 19656777; 20179738; 20301293; 20301314; 20617341; 21081970; 22025892; 22539340; 23401661 LTBP3 6716 4054 Geleophysic dysplasia 3; Dental anomalies and short stature AD/AR N/A N/A Craniofacial; Dental; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19344874; 25669657; 25899461; 27068007 LTBP4 6717 8425 Cutis laxa with severe pulmonary, gastrointestinal, and urinary abnormalities AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19836010 LTC4S 6719 4056 Asthma, aspirin-induced, susceptibility to AR Pediatric General Pharmacogenomic The relative risk/odds ratios of identified variants are overall relatively low, but variants may have pharmacogenomic importance 10970818; 19862937; 22884858; 23101307 LYRM4 21365 57128 Combined oxidative phosphorylation deficiency 19 AR N/A N/A Biochemical; Neurologic General Severe neonatal lactic acidosis has been described, but it is unclear if specific causative knowledge would be helpful in management (in one individual, supportive treatment in infancy has been described as beneficial) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23814038 LYRM7 28072 90624 Mitochondrial complex III deficiency, nuclear type 8 AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24014394 LYST 1968 1130 Chediak-Higashi syndrome AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Hematologic; Neurologic; Oncologic Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals can have infection susceptibility, and prophylaxis and early and aggressive treatment of infections can be beneficial; Surveillance for hematologic complications and malignancy is warranted; For the accelerated phase, chemoimmunotherapy then transition to continuation therapy can be beneficial; For bleeding, platelet transfusions and DDAVP may be beneficial to prevent and/or treat episodes; BMT/HSCT has been described 13584476; 5908967; 5156632; 5064229; 711501; 2697195; 2070553; 2058369; 8030398; 8701696; 9215680; 10422800; 10527680; 11857544; 15790783; 20503323; 20301751; 21488161; 23521865; 24521565 LYZ 6740 4069 Amyloidosis, systemic nonneuropathic AD N/A N/A Dermatologic; Gastrointestinal; Renal General The treatment of amyloidosis differs depending on the genetic cause (and genetic diagnosis may additionally help avoid relatively high-risk treatment regimens), and in lysozyme amyloidosis, liver and renal transplantation may be beneficial, but it is not clear that early (genetic) diagnosis would be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8464497; 15745733; 21988333 LZTFL1 6741 54585 Bardet-Biedl syndrome 17 AR N/A N/A Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition may involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17163542; 22510444; 23692385 LZTR1 6742 8216 Schwannomatosis 2; Noonan syndrome 10; Noonan syndrome 2 AD/AR Pediatric (Noonan syndrome 10; Noonan syndrome 2); Adult (Schwannomatosis 2) Cardiovascular; Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic Cardiovascular; Hematologic; Oncologic Individuals with Schwannomatosis are susceptible to schwannomas, and knowledge may allow early management; Individuals with Noonan syndrome may benefit from surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis or hypertrophic cardiomyopathy); Noonan syndrome can can include bleeding diathesis, and recognition and preventive measures (eg, in surgical situations) can be beneficial; Noonan syndrome can also include schwannomatosis as well as predisposition to other types of cancer, and knowledge may allow early management 24362817; 25480913; 25795793; 29469822; 30368668 M1AP 25183 130951 Spermatogenic failure 48 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32017041; 32673564 MAB21L1 6757 4081 Cerebellar, ocular, craniofacial, and genital syndrome AR N/A N/A Craniofacial; Dermatologic; Genitourinary; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27075597; 27103078; 30487245 MAB21L2 6758 10586 Microphthalmia/coloboma and skeletal dysplasia syndrome AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24906020 MACF1 13664 23499 Lissencephaly 9 with complex brainstem malformation AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24507697; 30471716 MAD2L2 6764 10459 Fanconi anemia, complementation group V AR Pediatric Craniofacial; Hematologic; Neurologic; Oncologic Hematologic; Oncologic Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); Individuals may be at risk for certain types of cancer, and awareness may allow early diagnosis and management; Surveillance for complications such as bone marrow failure is recommended 27500492 MADD 6766 8567 Developmental delay with endocrine, exocrine, autonomic, and hematologic abnormalities (DEEAH) syndrome AR Pediatric Craniofacial; Endocrine; Hematologic; Musculoskeletal; Neurologic Endocrine Among other findings, individuals have been described with endocrine anomalies (eg, hypoglycemia, thyroid dysfunction, growth hormone deficiency, and panhypopituitarism), and awareness may allow early diagnosis of medical management of these manifestations 28940097; 32761064 MAF 6776 4094 Ayme-Gripp syndrome AD Pediatric Allelic with Cataract 21, multiple types (AD) Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic Audiologic/Otolaryngologic In Ayme-Gripp syndrome, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 8834052; 8867660; 11772997; 16470690; 17935251; 24664492; 25865493 MAFA 23145 389692 Insulinomatosis and diabetes mellitus syndrome AD Pediatric Endocrine; Oncologic; Ophthalmologic Endocrine; Oncologic; Ophthalmologic The condition can include hypoglycemia due to insulomas, and management (with diazoxide and diet, though surgery has also been described) has been described as beneficial; Individuals have been described with glaucoma, and awareness may allow early diagnosis and management 19011561; 29339498 MAFB 6408 9935 Duane retraction syndrome-3 (DURS3) with or without deafness AD Pediatric Allelic with Multicentric carpotarsal osteolysis (AD) Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Renal Audiologic/Otolaryngologic Individuals with Multicentric carpotarsal osteolysis frequently have progressive renal disease Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 22387013; 27181683 MAG 6783 4099 Spastic paraplegia, autosomal recessive 75 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24482476; 26179919 MAGED2 16353 10916 Bartter syndrome type 5, antenatal transient XL Pediatric Renal Renal The condition can involve prenatal and postnatal manifestations, and awareness may allow medical management of electrolyte abnormalities during the transient period when children are affected 27120771 MAGEL2 6814 54551 Schaaf-Yang syndrome (Prader-Willi-like syndrome) AD Pediatric Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic Endocrine The condition has been described as including neonatal hyperinsulinemia hypoglycemia, and awareness may allow prompt management 24076603; 25473036; 26365340; 27195816; 28281571 MAGI2 18957 9863 Nephrotic syndrome 15 AR N/A N/A Renal General Renal transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27932480 MAGT1 28880 84061 Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia XL Pediatric Allelic with Mental retardation, X-linked 95 (XL); Congenital disorder of glycosylation, type Icc (XL) Allergy/Immunology/Infectious; Craniofacial; Neurologic Allergy/Immunology/Infectious For Mental retardation, X-linked 95, the evidence of variants as being related to disease causation has been questioned due to subsequent population-based studies Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 18455129; 21796205; 23871722; 25504528; 25956530; 31036665 MAK 6816 4117 Retinitis pigmentosa 62 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21835304 MALT1 6819 10892 Immunodeficiency 12 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described as suffering from primary immunodeficiency including infantile-onset recurrent bacterial and candidal infections, and awareness may allow prophylaxis and early and aggressive treatment of infections 23727036; 24332264 MAMLD1 2568 10046 Hypospadias 2, X-linked XL N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17086185 MAN1B1 6823 11253 Rafiq syndrome (Mental retardation, autosomal recessive 15) AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20345473; 21763484; 21063731 MAN2B1 6826 4125 Mannosidosis, alpha B, lysosomal AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical Manifestations can include immunodeficiency, and prophylactic vaccines and early and aggressive treatment of infections can be beneficial; Some individuals may manifest with early-onest hearing impairment, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Enzyme replacement therapy has been described as beneficial 4358183; 995502; 724292; 6860058; 4082921; 1472354; 8357013; 7702090; 9158146; 9758606; 11014473; 15534274; 18651971; 20301570; 22161967; 29716835; 31241255; 33317989 MANBA 6831 4126 Mannosidosis, beta A, lysosomal AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3762648; 2945113; 2079835; 1623631; 1499588; 8285582; 59034; 9384606; 12468273; 16401745; 17420068; 18565776; 19728872; 22369051 MAOA 6833 4128 Brunner syndrome XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8211186; 8503438; 20485326; 22365943; 24169519 MAP1B 6836 4131 Periventricular nodular heterotopia 9 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29738522; 30150678; 31317654 MAP2K1 6840 5604 Cardiofaciocutaneous syndrome 3 AD Pediatric Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Oncologic Cardiovascular; Oncologic Surveillance and treatment related to manifestations such as cardiac anomalies can be beneficial; Individuals may be at increased malignancy risk (eg, an individual with hepatoplastoma has been described), and awareness may allow prompt recognition and treatment of oncologic sequelae 16439621; 17551924; 17567882; 18456719; 18042262; 20301303; 20301365; 21495173 MAP2K2 6842 5605 Cardiofaciocutaneous syndrome 4 AD Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Oncologic Cardiovascular; Oncologic Surveillance and treatment related to manifestations such as cardiac anomalies can be beneficial; Individuals with malignancies have been reported (eg, hematologic malignancies), and awareness of increased risk may be beneficial in order to allow prompt detection and management 16439621; 8456719; 18042262; 20301365; 20358587; 21178588; 21495173 MAP3K1 6848 4214 46,XY sex reversal 6 AD Pediatric Endocrine; Genitourinary; Oncologic Genitourinary; Oncologic Surveillance and surgical treatment of gonadal tumors can reduce morbidity 12476449; 21129722 MAP3K14 6853 9020 Primary immunodeficiency with multifaceted aberrant lymphoid immunity AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described with recurrent bacterial, viral and Cryptosporidium infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT has been described 25406581 MAP3K20 17797 51776 Split-foot malformation with mesoaxial polydactyly; Myopathy, centronuclear 6, with fiber-type disproportion AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26755636; 27816943 MAP3K6 6858 9064 Familial gastric cancer AD Adult Oncologic Oncologic Awareness of the risk of diffuse gastric cancer may allow preventive measures and early diagnosis and treatment 25340522 MAP3K7 6859 6885 Cardiospondylocarpofacial syndrome AD Pediatric Allelic with Frontometaphyseal dysplasia 2 (AD) Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Ophthalmologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 10706363; 12503106; 20186786; 25899317; 27426733; 27426734 MAPK1 6871 5594 Noonan syndrome 13 AD Pediatric Cardiovascular; Dental; Craniofacial; Hematologic; Musculoskeletal; Neurologic Cardiovascular; Hematologic Among other findings, the condition can include congenital heart anomalies such as valvular abnormalities, and awareness may allow early diagnosis and management; Bleeding diathesis has been described, and awareness may allow preventative measures and early management of acute and chronic hematologic issues 32721402 MAPK10 6872 5602 Epileptic encephalopathy, Lennox-Gastaut type AD N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16249883; 23329067 MAPK8IP1 6882 9479 Diabetes mellitus AD N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10700186 MAPK8IP3 6884 23162 Neurodevelopmental disorder with or without variable brain abnormalities AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30612693; 30945334 MAPKAPK3 6888 7867 Macular dystrophy, patterned, 3 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23370609; 26744326 MAPKBP1 29536 23005 Nephronophthisis 20 AR N/A N/A Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28089251 MAPRE2 6891 10982 Congenital symmetric circumferential skin creases 2 AD N/A N/A Craniofacial; Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19182162; 21262397; 26637975 MAPT 6893 4137 Supranuclear palsy, progressive, 1; Frontotemporal dementia; Parkinson-dementia syndrome; Pick disease AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1416801; 7936288; 7936241; 7977375; 9029080; 9781517; 9789048; 10202939; 9443491; 9641683; 9708963; 9932968; 10072441; 10412802; 10534245; 10388790; 11134398; 11117542; 11445645; 11710889; 11601501; 11220749; 12177383; 12056930; 14595660; 12913211; 14991829; 15792962; 16195395; 10388790; 16278856; 17923640; 17310038; 18703462; 19884571; 19884572; 19786698; 21295377; 21555888; 21558644; 21943955; 22109955; 22482453; 22699846 MARCHF6 30550 10299 Epilepsy, familial adult myoclonic, 3 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14978679; 20548044; 31664039 MARK3 6897 4140 Visual impairment and progressive phthisis bulbi AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29771303 MARS1 6898 4141 Interstitial lung and liver disease AR Pediatric Allelic with Charcot-Marie-Tooth disease, axonal, type 2U (AD) Biochemical; Endocrine; Gastrointestinal; Hematologic; Neurologic; Pulmonary Hematologic While the condition may involve multiple issues related to medical care, the described individual had transfusion-dependent anemia, and awareness may allow prompt recognition and treatment 23729695; 24103465; 24354524; 25913036 MARS2 25133 92935 Combined oxidative phosphorylation deficiency 25; Spastic ataxia 3, autosomal recessive AR N/A N/A Biochemical; Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22448145; 25754315 MARVELD2 26401 153562 Deafness, autosomal recessive 49 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 15538632; 17186462; 18084694 MASP1 6901 5648 3MC syndrome 1 AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic Audiologic/Otolaryngologic The condition can include multiple congenital anomalies Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 690758; 17937425; 18266249; 21035106; 21258343 MASP2 6902 10747 MASP2 deficiency AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Surveillance and early treatments for autoimmune phenomena may be beneficial; Infectious sequelae have been reported, but the relation to immunosuppresion regimens is unclear 12904520; 19767106; 20338057 MAST1 19034 22983 Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30449657 MASTL 19042 84930 Thrombocytopenia 2 AD Pediatric Hematologic Hematologic Individuals may have bleeding tendency, and precautions (eg, in surgical situations) may be beneficial 10891439; 12890928; 22102272 MAT1A 6903 4143 Methionine adenosyltransferase I/III deficiency AD/AR Pediatric Biochemical; Neurologic Biochemical While the disorders frequently do not have severe sequelae, and therapy may not be required for many individuals, in some, dietary measures (eg, methionine restriction) may be beneficial; AdoMet therapy has also been described as beneficial 1191305; 7229751; 7271238; 3812486; 3339126; 1683972; 1527987; 7573050; 7560086; 8770875; 9042912; 9482646; 12705496 MATN3 6909 4148 Epiphyseal dysplasia, multiple, 5; Spondyloepimetaphyseal dysplasia, Borochowitz-Cormier-Daire type AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13849708; 11479597; 11528506; 12884427; 15121775; 14729835; 15948199; 18205203; 20301302; 21922596; 21965141 MATR3 6912 9782 Amyotrophic lateral sclerosis 21 AD N/A N/A Audiologic/Otolaryngologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9837826; 19344878; 24686783; 25154462 MAX 6913 4149 Pheochromocytoma AD Pediatric Oncologic Oncologic Surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of neoplasms, which may may reduce morbidity and mortality 21685915 MBD5 20444 55777 Mental retardation, autosomal dominant 1 AD N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17847001; 21981781 MBL2 6922 4153 Mannose-binding protein deficiency AD Pediatric Biochemical Pharmacogenomic Low MBL levels are associated with increased risk of infection in young children, cancer patients undergoing chemotherapy, and organ-transplant patients treated with immunosuppressive regimens, especially liver transplant recipients 21871896 MBOAT7 15505 79143 Mental retardation, autosomal recessive 57 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27616480 MBTPS1 15456 8720 Spondyloepiphyseal dysplasia, Kondo-Fu type AR N/A N/A Craniofacial; Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30046013 MBTPS2 15455 51360 Keratosis follicularis spinulosa decalvans, X-linked; IFAP syndrome 1 with or without BRESHECK syndrome; Olmsted syndrome, X-linked; Osteogenesis imperfecta, type XIX XL N/A N/A Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1552542; 10398262; 10694306; 8745901; 18984066; 19361614; 20672378; 22105905; 24313295; 27380894 MC1R 6929 4157 Increased analgesia from kappa-opioid receptor agonist, female specific AD Pediatric Allelic with Skin/hair/eye pigmentation, variation in, 2 (AD) General Pharmacogenomic Skin/hair/eye pigmentation, variation in may not have actionable relevance, though there may be increased risk of skin cancer Variants may have pharmacogenomic relevance, as results suggest that women with 2 variant MC1R alleles demonstrate greater analgesia from kappa-opioid pentazocine 7581459; 8894704; 11030758; 10631149; 11487574; 11500805; 11500806; 12876664; 12839583; 12663858; 16809487; 17952075; 19578364; 21693730; 21128237; 22095472; 22561518 MC2R 6930 4158 Glucocorticoid deficiency 1 AR Pediatric Endocrine Endocrine Early recognition and preventive measures and treatment related to hypoglycemia (as well as to potential infectious episodes) can be effective 13616862; 4302512; 4312011; 4342294; 4349230; 238474; 2539720; 8094489; 8227361; 7627261; 12851305; 21823545; 22337906; 22814974 MC3R 6931 4159 Obesity, severe, susceptibility to, 9 AD N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11889220; 18231126; 21047972 MC4R 6932 4160 Obesity, autosomal dominant AD N/A N/A Endocrine General Biallelic variants have been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9771698; 9771699; 10199800; 10577903; 11487744; 12646665; 12499395; 12646666; 14764818; 16507637; 16492696; 20957447; 20966905; 21047921; 21921657; 22463805 MCCC1 6936 56922 3-Methylcrotonyl-CoA carboxylase 1 deficiency AR Pediatric Biochemical; Neurologic Biochemical Therapy may not be necessary/effective in some individuals, but medical (eg, carnitine, glycine) and dietary (eg, low protein, leucine restricted) therapy may be beneficial in some individuals; Precautions in the setting of stressors such as viral illnesses may be beneficial 4194964; 5035417; 1000869; 6441868; 2515383; 1779635; 1517917; 8598648; 9187484; 10485305; 11181649; 11170888; 11893004; 16835865; 17968484; 21734494; 22264772; 22642865; 25356967 MCCC2 6937 64087 3-Methylcrotonyl-CoA carboxylase 2 deficiency AR Pediatric Biochemical; Neurologic Biochemical Therapy may not be necessary/effective in some individuals, but medical (eg, carnitine, glycine) and dietary (eg, low protein, leucine restricted) therapy may be beneficial in some individuals; Precautions in the setting of stressors such as viral illnesses may be beneficial 7128647; 1293382; 8598650; 8831079; 9544913; 11181649; 11170888; 15877210; 16835865; 17968484; 22030835; 22264772; 22642865; 25356967 MCEE 16732 84693 Methylmalonyl-CoA epimerase deficiency AR N/A N/A Biochemical; Neurologic; Ophthalmologic Biochemical No response to vitamin B12 administration was documented in the affected individual Long-term dietary (high-calorie diet low in propiogenic amino acid precursors with carnitine supplementation) and medical management (eg, IM hydroxocobalamin, antibiotics to decrease propionate production) is indicated; Fasting and high-protein consumption should be avoided; In the emergent setting, prompt recognition and appropriate metabolic care may be beneficial to decrease morbidity and mortality; Antioxidants for optic nerve atrophy may be beneficial; Liver/kidney transplant has been described in methylmalonic acidemia 16752391; 17823972; 20301409 MCFD2 18451 90411 Factor V & Factor VIII, combined deficiency of AR Pediatric Hematologic Hematologic Preventive measures and prompt treatment of bleeding diathese may reduce morbidity; Medical treatment to replace absent factors can be effective (eg, with FFP for FV, Desmopression or FVIII concentrates/recombinant products/plasma-derived factor for FVIII) 12717434; 15333032; 16304051; 19141160; 18391077; 21492322; 22535353 MCIDAS 40050 345643 Ciliary dyskinesia, primary, 42 AR Pediatric Allergy/Immunology/Infectious; Neurologic; Pulmonary Allergy/Immunology/Infectious; Pulmonary Pulmonary surveillance may be beneficial to assess respiratory function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 25048963; 30237576 MCM10 18043 55388 Immunodeficiency 80 with or without congenital cardiomyopathy AR Pediatric Allergy/Immunology/Infectious; Cardiovascular Allergy/Immunology/Infectious; Cardiovascular Individuals are susceptible to severe infections, and early and aggressive management may be beneficial related to morbidity and mortality; BMT has been described; Individuals have been described with cardiomyopathy, and early diagnosis may allow management 32865517; 33712616 MCM2 6944 4171 Deafness, autosomal dominant 70 AD N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26196677 MCM3AP 6946 8888 Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24123876; 28633435; 28969388; 29982295 MCM4 6947 4173 Immunodeficiency 54 AR Pediatric Allergy/Immunology/Infectious; Endocrine; Musculoskeletal; Oncologic Allergy/Immunology/Infectious; Endocrine; Oncologic Individuals are susceptible to recurrent infections, and early and aggressive management may be beneficial related to morbidity and mortality; Adrenal insufficiency has been described, and medical management (with corticosteroids) has been described; Individuals have been suggested to have susceptibility to cancer, and awareness may allow early detection and management 14702466; 17142786; 22354167; 22354170 MCM5 6948 4174 Meier-Gorlin syndrome 8 AR N/A N/A Craniofacial; Genitourinary; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28198391 MCM6 6949 4175 Lactose intolerance, adult type; Lactase persistence AD N/A N/A Biochemical; Gastrointestinal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7543318; 9481112; 11788828; 12915462; 15114531; 16041375; 15928901; 16019716; 17120047; 17159977; 18179885 MCM8 16147 84515 Premature ovarian failure 10 AR Pediatric Endocrine; Obstetric Endocrine Unlike some other forms of Premature ovarian failure, measures to allow fertility through egg preservation may not be helpful Individuals have been described with manifestations including hypothyroidism and hypergonadotropic hypogonadism, and response to hormonal therapy has been described as being beneficial 25437880; 25873734 MCM9 21484 254394 Ovarian dysgenesis 4 AR Pediatric Endocrine Endocrine Awareness may allow medical management (eg, with combined estrogen-progestin therapy) in order to benefit pubertal development and growth 25480036 MCOLN1 13356 57192 Mucolipidosis IV AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4365943; 166049; 7114093; 3918453; 2438637; 1789285; 9323557; 9600972; 9710036; 10973263; 11030752; 15523648; 17239335; 19006653; 20159435 MCPH1 6954 79648 Microcephaly, primary autosomal recessive, 1 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7693575; 12046007; 11857108; 15199523; 16311745; 20978018; 20101680; 21668957 MDH1 6970 4190 Developmental and epileptic encephalopathy 88 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31538237 MDH2 6971 4191 Developmental and epileptic encephalopathy 51 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27989324 MDM2 6973 4193 Lessel-Kubisch syndrome AR Pediatric Craniofacial; Dermatologic; Endocrine; Renal Renal Among other features, the condition may involve renal failure associated with severe hypertension, and awareness may allow early diagnosis and management 28846075 MDM4 6974 4194 Bone marrow failure syndrome 6 AD Pediatric Hematologic; Oncologic Hematologic; Oncologic Individuals (including based on family history) have been described with bone marrow failure as well as apparent increased risk of malignancies, and awareness may allow prompt management 32300648 MECOM 3498 2122 Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 AD Pediatric Allergy/Immunology/Infectious; Hematologic; Musculoskeletal Allergy/Immunology/Infectious; Hematologic The condition involves bone marrow failure, and awareness may allow prompt management of hematologic complications as well as complications related to susceptibility to infections; HSCT has been described 20091385; 26581901 MECP2 6990 4204 Rett syndrome; Encephalopathy, neonatal severe, due to MECP2 mutations; Autism, X-linked 3; Mental retardation, X-linked syndromic 13; Angelman-like syndrome; Mental retardation, X-linked 79; Mental retardation, X-linked syndromic, Lubs type XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5300597; 8651288; 9377804; 9326329; 9637791; 10508514; 10232754; 10398236; 10577905; 10986043; 11106359; 12615169; 11071498; 11022934; 11768391; 11309367; 11402105; 11746022; 11913564; 11930274; 11807877; 11885030; 12325019; 12615169; 12770674; 14598336; 12615169; 12615169; 15034579; 16077729; 15689435; 16080119; 17172942; 16965328; 17088400; 16690727; 16832102; 17712354; 17351020; 18477000; 18989701; 19194883; 18985075; 19365833; 20035514; 20425814; 21154482; 21104896; 22415763; 22578097; 22581587 MECR 19691 51102 Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities (DYTOABG) AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27817865 MED12 11957 9968 Lujan-Fryns syndrome; Opitz-Kaveggia syndrome; Mental retardation, X-linked, with Marfanoid habitus; FG syndrome; Ohdo syndrome, X-linked XL N/A N/A Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic General Aortic root dilatation and ventricular septal defect were reported in one individual and his maternal uncle Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4365204; 6711603; 3322000; 10405444; 10508979; 17036352; 17334363; 17369503; 18973276; 19938245; 20301719; 20507344; 20981778; 23395478 MED12L 16050 116931 Nizon-Isidor syndrome AD N/A N/A Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31155615 MED13 22474 9969 Intellectual developmental disorder, autosomal dominant 61 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29740699 MED13L 22962 23389 Transposition of the great arteries, dextro-looped 1; Mental retardation and distinctive facial features with or without cardiac defects; Congenital heart defects and intellectual disability; Intellectual disability, autosomal recessive AD/AR N/A N/A Cardiovascular; Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14638541; 21937992; 23403903; 24781760; 25137640; 25356899; 25712080 MED17 2375 9440 Microcephaly, postnatal progressive, with seizures and brain atrophy AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20950787 MED23 2372 9439 Mental retardation, autosomal recessive 18 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21868677 MED25 28845 81857 Basel-Vanagait-Smirin-Yosef syndrome; Charcot-Marie-Tooth disease, axonal, tybe 2B2 AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Neurologic; Ophthalmologic General Basel-Vanagait-Smirin-Yosef syndrome can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19290556; 25792360 MED27 2377 9442 Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33443317 MEF2C 6996 4208 Mental retardation, autosomal dominant 20 AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19876902; 19592390; 20412115; 20513142; 23001426 MEFV 6998 4210 It has been described that heterozygous variants, while potentially contributing to/causing certain autoinflammatory disorders, do not cause classic (Mendelian) Familial Mediterranean fever, but may act as risk alleles (susceptibility factors) for clinically similar forms of disease AD/AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Musculoskeletal; Renal Allergy/Immunology/Infectious It has been described that heterozygous mutations, while potentially contributing to/causing certain autoinflammatory disorders, do not cause classic (Mendelian) Familial Mediterranean fever, but may act as risk alleles (susceptibility factors) for clinically similar forms of disease Individuals with Familial Mediterranean Fever may present with periodic fever, pain (including abdominal pain, arthritis, pleurisy), and rash,and medical treatment aimed at reducing inflammation (eg, with colchicine, TNF-alpha antibodies, IL-1 decoy receptor agents) can be effective (and additional considerations related to medical treatment prior to and during pregnancy may be beneficial); BMT has been reported; Individuals with Neutrophilic dermatosis, acute febrile have been described with pediatric onset of recurrent fever and dermatologic abnormalities, and treatment (eg, with corticosteroids, adalimumab, and TNFA antagonist) has been described as potentially beneficial but not completely effective. 14162896; 4437392; 4636899; 4783424; 921085; 6822630; 3966749; 3306755; 3515182; 3694919; 8434621; 8831074; 9288094; 9288758; 9415347; 9266193; 9450890; 10528243; 10787449; 12130485; 12529300; 14679589; 15024744; 16632148; 20301405; 23075349; 23070486; 23463692; 23508419; 23505238; 23521609; 23710607; 23716950; 23742958; 23800337; 23844200; 27030597; 28835462; 31998953 MEGF10 29634 84466 Myopathy, areflexia, respiratory distress, and dysphagia, early-onset AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17236770; 22101682; 22371254; 23453856 MEGF8 3233 1954 Carpenter syndrome 2 AR N/A N/A Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal General The condition can include multiple malformations, including cardiac and genitourinary malformations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23063620 MEI1 28613 150365 Hydatidiform mole, recurrent, 3 AR Pediatric Obstetric; Oncologic Obstetric; Oncologic Women are likely to have pregnancies with hydatidiform moles, and awareness may allow reproductive planning and/or surveillance measures, which may allow early detection and treatment 30388401 MEIOB 28569 254528 Spermatogenic failure 22 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28206990 MEIS2 7001 4212 Cleft palate, cardiac defects, and mental retardation (CPCMR) AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General The condition can include multiple malformations, including cardiac malformations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24678003; 25712757; 26561393; 27225850 MEN1 7010 4221 Multiple endocrine neoplasia type I; Hyperparathyroidism, familial primary AD Adult Endocrine; Oncologic Endocrine; Oncologic Surveillance and early detection of and treatment for neoplasms, as well as related sequelae may allow treatment (eg, with PPIs/somatostatin analogs, as well as appropriate and tailored surgical interventions and follow-up), and may decrease morbidity and mortality 6108714; 2857681; 9215689; 9103196; 9236523; 9215690; 9463336; 9683585; 9554741; 9832038; 9506756; 9709923; 9792884; 10439966; 10193936; 11344233; 11739416; 11295574; 12417605; 12050235; 11836268; 12112656; 12791038; 15531478; 14871962; 15240620; 15292304; 14985373; 17879353; 20301710; 22522645; 22549346; 22581216; 22584706; 23052745; 23376981; 23443490; 23645327; 23652667; 23809488; 23919339; 23956349; 23961499; 24014011; 24037737; 24058102 MEOX1 7013 4222 Klippel-Feil syndrome 2 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23290072; 24073994 MERTK 7027 10461 Retinitis pigmentosa 38 AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11062461; 11727200; 17301963; 22180149 MESD 13520 23184 Osteogenesis imperfecta, type XX AR N/A N/A Dental; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31564437 MESP2 29659 145873 Spondylocostal dysostosis 2, autosomal recessive AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15214000; 15122512; 18485326; 20301771 MET 7029 4233 Renal cell carcinoma, papillary; Deafness, autosomal recessive 97 AD/AR Pediatric (Deafness, autosomal recessive 97); Adult (Renal cell carcinoma, papillary) Allelic with Osteofibrous dysplasia, susceptibility to (AD) Audiologic/Otolaryngologic; Musculoskeletal; Oncologic Audiologic/Otolaryngologic; Oncologic In Renal cell carcinoma, papillary, surveillance and/or awareness of cancer risk may yield early detection of neoplasms may allow early treatment, which may reduce morbidity and mortality; In Deafness, autosomal recessive 97, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 1270474; 9140397; 9234973; 9563489; 9731534; 19402075; 22717761; 25941349; 26637977 METTL13 24248 51603 Deafness, nonsyndromic, modifier 1 AD N/A N/A Audiologic/Otolaryngologic General Heterozygous variants have a protective effect (related to nonsyndromic deafness) for individuals with homozygous pathogenic variants in GAB1 Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29408807 METTL23 26988 124512 Mental retardation, autosomal recessive 44 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24501276; 24626631 METTL5 25006 29081 Intellectual developmental disorder, autosomal recessive 72 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29302074; 31564433 MFAP5 29673 8076 Aortic aneurysm, familial thoracic 9 AD Pediatric Cardiovascular Cardiovascular Individual have been described with aortic dilatation and arrhthymias, and awareness may allow surveillance and early medical and/or surgical management, which may reduce morbidity and mortality 25434006 MFF 24858 56947 Encephalopathy due to defective mitochondrial and peroxisomal fission 2 AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22499341; 26783368; 32181496 MFN2 16877 9927 Charcot-Marie-Tooth disease, type 2A2A; Charcot-Marie-Tooth disease, type 2A2B; Hereditary motor and sensory neuropathy, type VIA AD/AR N/A N/A Neurologic; Ophthalmologic General Charcot-Marie-Tooth disease, type 2A2 typically (though not always) results from heterozygous mutations; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9409358; 11148244; 12601114; 15136675; 15064763; 16043786; 16087932; 16835246; 16437557; 17309650; 18946002; 20008656; 19889647; 21715711; 22206013; 22526351; 22546700; 22653593; 22762946; 22957060; 30649465 MFRP 18121 83552 Microphthalmia, isolated 5; Nanophthalmos 2; Retinitis pigmentosa, autosomal recessive AR N/A N/A Ophthalmologic General Individuals are at risk for ophthalmologic features such as retinal detachment Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1258954; 15976030; 17167404; 18554571; 19526372; 20361016; 21810984; 22565643; 22605927; 23112574 MFSD2A 25897 84879 Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities (Microcephaly 15, primary, autosomal recessive) AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26005865; 26005868 MFSD8 28486 256471 Ceroid lipofuscinosis, neuronal, 7 AR Pediatric Biochemical; Neurologic; Ophthalmologic Neurologic The condition can include severe sequelae, including seizures, and use of a patient-specific antisense oligonucleotide has been reported as benefiting clinical findings, including related to seizure control 15074367; 15965709; 17564970; 19277732; 19201763; 18850119; 22612257; 31597037 MGAT2 7045 4247 Congenital disorder of glycosylation, type IIa AR Pediatric Audiologic/Otolaryngologic; Biochemical; Craniofacial; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 7944531; 8808595; 11228641; 19419693; 20684000; 22105986; 23023920 MGME1 16205 92667 Mitochondrial DNA depletion syndrome 11 AR Pediatric Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic Cardiovascular In addition to other manifestations, the condition has been described as including cardiovascular sequelae (eg, dilated cardiomyopathy, arrhythymias), and awareness may allow appropriate surveillance and prompt management 23313956 MGP 7060 4256 Keutel syndrome AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6468443; 3717211; 2515061; 9674914; 9916809; 15810001 MIA3 24008 375056 Ondontochondrodysplasia 2 with hearing loss and diabetes AR Pediatric Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal; Neurologic Audiologic/Otolaryngologic; Endocrine Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; The condition can involved insulin-dependent diabetes mellitus, and awareness may enable early medical management 32101163 MIB1 21086 57534 Left ventricular noncompaction 7 AD Pediatric Cardiovascular Cardiovascular Left ventricular noncompaction may manifest as depressed systolic function, with potential complications including arrhythmias, systemic embolism, heart failure and sudden death, and surveillance (eg, with echocardiogram and electrocardiogram) may allow early diagnosis and treatment 23314057 MICOS13 33702 125988 Combined oxidative phosphorylation deficiency 37 AR N/A N/A Biochemical; Cardiovascular; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27623147; 29618761; 27485409 MICU1 1530 10367 Myopathy with extrapyramidal signs AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24336167; 27123478; 29721912 MID1 7095 4281 Opitz GBBB syndrome, type I XL N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9354791; 11030761; 12833403; 15121778; 15558842; 16619207; 20301502; 20671548; 22407675 MID2 7096 11043 Mental retardation, X-linked 101 XL N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24115387 MIEF2 17920 125170 Combined oxidative phosphorylation deficiency 49 AR Pediatric Biochemical; Musculoskeletal Biochemical The condition has been described as involving muscle weakness and pain, and medical management (eg, with riboflavin and coenzyme Q10) has been described as beneficial 29361167 MIP 7103 4284 Cataract 15, multiple types AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10802646 MIPEP 7104 4285 Combined oxidative phosphorylation deficiency 31 AR Pediatric Biochemical; Cardiovascular; Craniofacial; Neurologic; Ophthalmologic Cardiovascular The condition can include hypertrophic cardiomyopathy, and awareness may allow early diagnosis and interventions 27799064 MIR140 31527 406932 Spondyloepiphyseal dysplasia, Nishimura type AD N/A N/A Craniofacial; Musculoskeletal; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30804514 MIR17HG 23564 407975 Feingold syndrome 2 AD N/A N/A Cardiovascular; Endocrine; Musculoskeletal; Neurologic General The condition can involve structural cardiac anomalies, and screening with echocardiography has been recommended; Due to endocrine findings, testing for growth hormone deficiency has been recommended in order to enable consideration of medical management 21892160; 30672094 MIR184 31555 406960 Keratoconus with cataract AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14638698; 16735990; 21996275; 22131394 MIR204 31582 406987 Retinal dystrophy and iris coloboma with or without congenital cataract AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26056285 MIR96 31648 407053 Deafness, autosomal dominant 50 AD Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Hearing loss was progressive, and was described in the earliest reported affected at 12 years in one family, while it occurred as early as 2-3 years of age in another family Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 14757864; 19363479 MITF 7105 4286 Waardenburg syndrome, type 2A; Tietz albinism-deafness syndrome; Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (COMMAD); Melanoma, cutaneous malignant, susceptibility to, 8; Renal cell carcinoma with or without malignant melanoma AD Pediatric (Waardenburg syndrome, type 2A; Tietz albinism-deafness syndrome; Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (COMMAD)); Adult (Melanoma, cutaneous malignant, susceptibility to, 8; Renal cell carcinoma with or without malignant melanoma) Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Musculoskeletal; Ophthalmologic; Oncologic Audiologic/Otolaryngologic; Oncologic Digenic inheritance (with TYR) has been reported For Waardenburg syndrome, type 2A, Tietz albinism-deafness syndrome, and COMMAD, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; For Melanoma, cutaneous malignant, susceptibility to and Renal cell carcinoma with or without malignant melanoma, awareness may allow preventive measures, surveillance, and early diagnosis and treatment of disease 13985019; 5006208; 331943; 666627; 7951321; 7874167; 7702105; 7573125; 8589691; 9158138; 10851256; 18510545; 20024939; 22012259; 22080950; 23167872; 23414473; 23774529; 23802662; 24638154; 24767713; 27889061 MKKS 7108 8195 McKusick-Kaufman syndrome; Bardet-Biedl syndrome 6 AR N/A N/A Cardiovascular; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The conditions frequently involve multiple congenital anomalies and multisystemic manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Variants may modify severity of BBS and related disorders due to variants in other BBS-associated genes 14172277; 5694533; 5545396; 7262101; 7246610; 2681663; 2564737; 8209897; 10465109; 10973251; 11102925; 10802661; 11567139; 12837689; 15637713; 16104012; 20301537; 20301675; MKRN3 7114 7681 Central precocious puberty AD N/A N/A Endocrine General In Precocious puberty, treatment with gonadotropin-releasing hormone receptor analogs/LHRH agonists can be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Variants may modify severity of BBS and related disorders due to variants in other BBS-associated genes 23738509 MKS1 7121 54903 Joubert syndrome 28; Meckel syndrome 1; Bardet-Biedl syndrome 13 AR N/A N/A Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The conditions frequently involve multiple congenital anomalies and multisystemic manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Variants may modify severity of BBS and related disorders due to variants in other BBS-associated genes 6486167; 16415886; 17377820; 17935508; 18327255; 19515853; 20301537; 24608809; 24886560 MLC1 17082 23209 Megalencephalic leukoencephalopathy with subcortical cysts 1 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11254442; 12939431; 18757878; 20301707; 20560255; 21145992; 21160490; 21487377; 22416245; 22552818; 24824219 MLH1 7127 4292 Colorectal cancer, hereditary nonpolyposis, type 2; Mismatch repair cancer syndrome 1; Endometrial cancer; Muir-Torre syndrome AD/AR Adult (Colorectal cancer, hereditary nonpolyposis, type 2; Endometrial cancer; Muir-Torre syndrome)/Pediatric (Mismatch repair cancer syndrome) Dermatologic; Oncologic Oncologic Individuals may be at risk for a number of types of cancer; Variants may also contribute to cancer susceptibility in the general population In HNPCC, for surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types (indiviudals may be at risk for a number of cancer types), awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; Individuals with Mismatch repair cancer syndrome are at risk of multiple types of malignancy, and awareness may allow early detection and management 6020987; 5684233; 4063166; 7815421; 8128251; 8145827; 7661930; 8751876; 9634524; 9927033; 10072435; 10577927; 15264268; 15077197; 16042583; 15520370; 15662714; 15235030; 17440981; 18457354; 19156169; 20301390; 24434690 MLH3 7128 27030 Colorectal cancer, hereditary nonpolyposis type 7; Endometrial carcinoma AD Adult Oncologic Oncologic The clinical significance of mutations in this gene is unclear Surveillance to allow early detection and treatment of tumors (associated with colorectal cancer) may be beneficial to reduce morbidity and mortality 12702580; 16885347 MLPH 29643 79083 Griscelli syndrome, type 3 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12148598; 12897212 MLYCD 7150 23417 Malonyl-CoA decarboxylase deficiency AR Pediatric Biochemical; Cardiovascular; Neurologic Biochemical; Cardiovascular Dietary measures (low-fat, high-carbohydrate diet, with one report describing benefit from long-chain triglyceride restriction and medium-chain triglyceride supplementation) can normalize urinary organic acid excretion and prevent hypoglycemic episodes; During infectious/febrile illnesses, inpatient care to reduce morbidity and mortalitiy may be beneficial; Surveillance for cardiac manifestations may allow early management, which may be beneficial 6145813; 3709568; 8259873; 10417274; 9869665; 10455107; 12955715; 16275149; 20549361; 22104738; 22778304; 31395333 MMAA 18871 166785 Methylmalonic acidemia, cblA type AR Pediatric Biochemical; Hematologic; Neurologic; Ophthalmologic Biochemical Long-term dietary (high-calorie diet low in propiogenic amino acid precursors with carnitine supplementation) and medical management (eg, IM hydroxocobalamin, antibiotics to decrease propionate production) is indicated; Fasting and high-protein consumption should be avoided; In the emergent setting, prompt recognition and appropriate metabolic care may be beneficial to decrease morbidity and mortality; Antioxidants for optic nerve atrophy may be beneficial; Liver/kidney transplant has been described in methylmalonic acidemia 6132336; 12438653; 20301409; 21545677; 23026888 MMAB 19331 326625 Methylmalonic acidemia, cblB type AR Pediatric Biochemical; Hematologic; Neurologic; Ophthalmologic Biochemical Long-term dietary (high-calorie diet low in propiogenic amino acid precursors with carnitine supplementation) and medical management (eg, IM hydroxocobalamin, antibiotics to decrease propionate production) is indicated; Fasting and high-protein consumption should be avoided; In the emergent setting, prompt recognition and appropriate metabolic care may be beneficial to decrease morbidity and mortality; Antioxidants for optic nerve atrophy may be beneficial; Liver/kidney transplant has been described in methylmalonic acidemia 7213387; 12471062; 16410054; 20301409; 20301503; 20556797; 21416195; 24813872 MMACHC 24525 25974 Methylmalonic aciduria and homocystinuria, cblC type AR/Digenic Pediatric Biochemical; Cardiovascular; Dermatologic; Hematologic; Neurologic; Ophthalmologic; Renal Biochemical Compound heterozygosity and digenic inheritance (with PRDX1) has been described While no treatment is completely effective, specific dietary (eg, high-calorie, low protein diet and avoidance of fasting, with measures taken to avoid/treat decompensation) and other medical measures (eg, cofactor therapy) may be beneficial to treat and prevent sequelae in the acute and chronic states 5779140; 6749192; 3257264; 2368803; 9266389; 11258350; 10399092; 11320193; 12210350; 16311595; 16714133; 17431913; 17853453; 20301503; 19370762; 20631720; 21748409; 21835369; 23837176; 29302025 MMADHC 25221 27249 Methylmalonic aciduria and homocystinuria, cblD type AR Pediatric Biochemical; Hematologic; Neurologic; Ophthalmologic Biochemical While no treatment is completely effective, specific dietary (eg, high-calorie, low protein diet and avoidance of fasting, with measures taken to avoid/treat decompensation) and other medical measures (eg, cofactor therapy) may be beneficial to treat and prevent sequelae in the acute and chronic states 5524089; 2339678; 15292234; 18385497; 20301409; 20301503; 22156578 MME 7154 4311 Spinocerebellar ataxia 43; Charcot-Marie-Tooth disease, axonal, type 2T AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26991897; 27583304 MMP13 7159 4322 Spondyloepimetaphyseal dysplasia, Missouri type (Metaphyseal anadysplasia 1); Metaphyseal dysplasia, Spahr type AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13915518; 16167086; 19615667; 24648384; 24781753 MMP14 7160 4323 Winchester syndrome AR N/A N/A Biochemical; Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4238825; 22922033 MMP19 7165 4327 Cavitary optic disc anomalies AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17368552; 17362864; 25581579 MMP2 7166 4313 Multicentric osteolysis, nodulosis, and arthropathy (Torg-Winchester syndrome) AR N/A N/A Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5795345; 2625626; 9843039; 10861676; 10861675; 11431697; 15691365; 16542393; 17059372; 20720557; 20865259; 22876575 MMP20 7167 9313 Amelogenesis imperfecta, hypomaturation type, IIA2 AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3150442; 15744043; 21597265; 23355523 MMP21 14357 118856 Heterotaxy, visceral, 7 AR N/A N/A Cardiovascular; Gastrointestinal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25807483; 26437028; 26437029 MMP9 7176 4318 Metaphyseal anadysplasia 2 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4252978; 1867263; 19615667 MMUT 7526 4594 Methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency AR Pediatric Biochemical; Hematologic; Cardiovascular; Neurologic; Ophthalmologic Biochemical Long-term dietary (high-calorie diet low in propiogenic amino acid precursors with carnitine supplementation) and medical management (eg, IM hydroxocobalamin, antibiotics to decrease propionate production) is indicated; Fasting and high-protein consumption should be avoided; In the emergent setting, prompt recognition and appropriate metabolic care may be beneficial to decrease morbidity and mortality; Antioxidants for optic nerve atrophy may be beneficial; Liver/kidney transplant has been described in methylmalonic acidemia 6132336; 1977311; 1970180; 1968706; 1346616; 1351030; 7681251; 15643616; 12948746; 16451139; 18563634; 20301409; 22614770; 22695176 MN1 7180 4330 CEBALID syndrome; Meningioma, familial AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic Audiologic/Otolaryngologic; Oncologic CEBALID syndrome may include early-onset hearing loss among other features, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Meningomia, familial, surveillance for neoplasms to enable early treatment may improve outcomes 2014801; 7731706; 31834374; 31839203 MNS1 29636 55329 Heterotaxy, visceral, 9, autosomal, with male infertility AR N/A N/A Cardiovascular; Gastrointestinal; Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30148830; 31534215 MNX1 4979 3110 Currarino syndrome AD Pediatric Gastrointestinal; Genitourinary; Musculoskeletal; Oncologic; Renal Oncologic The condition can involve multiple congenital anomalies While congenital malformations often allow clinical recognition, individuals can have presacral teratomas, which can undergo malignant transformation, and awareness may allow prompt detection and management 6789651; 2059799; 9843207; 10749657; 11528505; 15216552; 16906559; 17612791 MOCOS 18234 55034 Xanthinuria, type II AR Pediatric Biochemical; Musculoskeletal; Renal Biochemical; Renal Most individuals are described as asymptomatic, but xanthine deposition can lead to myositis, urinary tract calculi, and acute renal failure and dietary measures (eg, purine restricted, increased fluid intake) and medical measures (eg, allopurinol) may be beneficial 11302742; 14624414; 17368066; 25967871 MOCS1 7190 4337 Molybdenum cofactor deficiency, type A AR Pediatric Biochemical; Neurologic; Ophthalmologic Biochemical The disorder can have severe neurologic sequelae, and the use of substitution therapy (with IV-administered purified cyclic pyranopterin monophosphate) has been reported as showing benefit in biochemical parameters as well as clinical/neurologic manifestations 9731530; 10053004; 10327149; 16021469; 20385644; 21031595 MOCS2 7193 4338 Molybdenum cofactor deficiency, type B AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11746050; 16021469; 16429380; 19544009; 21031595 MOG 7197 4340 Narcolepsy 7 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21907016 MOGS 24862 7841 Congenital disorder of glycosylation, type IIb AR Pediatric Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Hematologic; Musculoskeletal; Neurologic Hematologic Hepatic-metabolized agents should be avoided At least theoretically, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 10788335; 20301507; 24716661 MORC2 23573 22880 Charcot-Marie-Tooth disease type, axonal, type 2Z; Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26497905; 27105897; 28771897; 32693025 MPC1 21606 51660 Mitochondrial pyruvate carrier deficiency AR N/A N/A Biochemical; Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12649063; 22628558 MPDU1 7207 9526 Congenital disorder of glycosylation, type If AR Pediatric Biochemical; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Hematologic Hepatic-metabolized agents should be avoided At least theoretically, awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 11733556; 11733564; 20301507 MPDZ 7208 8777 Hydrocephalus, nonsyndromic, autosomal recessive 2 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23240096 MPEG1 29619 219972 Immunodeficiency 77 AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described with recurrent and severe polymicrobial infections, including involving with unusual organisms, and awareness may allow preventative measures and early and aggressive management of infections and related sequelae (eg, treatment with gamma-IFN has been suggested to be as a potentially effective therapeutic modality) 28422754; 33224153 MPI 7216 4351 Congenital disorder of glycosylation, type Ib AR Pediatric Biochemical; Gastrointestinal; Hematologic Biochemical; Hematologic Hepatic-metabolized agents should be avoided Treatment with oral mannose can result in clinical improvement; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 9585601; 9525984; 10484808; 10980531; 11134235; 12414827; 18285818; 19065443; 19101627; 20301507; 20679665 MPIG6B 13937 80739 Thrombocytopenia, anemia, and myelofibrosis AR Pediatric Hematologic; Oncologic Hematologic; Oncologic Individuals have been described with myelofibrosis and early-childhood onset thrombocytopenia and anemia, and the use of RBC transfusions have been described (as well as iron and B12/folic acid) 27743390 MPL 7217 4352 Thrombocythemia 2; Amegakaryocytic thrombocytopenia AD/AR Pediatric Hematologic; Oncologic Hematologic; Oncologic For Thrombocythemia 2, manifestations may include thrombotic/hemorrhagic episodes, as well as leukemic transformation, and surveillance and prompt treatment may be beneficial; For Amegakaryocytic thrombocytopenia, individuals may have findings such as severe bleeding complications, and platelet transfusion can be beneficial; Effective SCT has been described 9029014; 10077649; 11133753; 14764528; 15269348; 16351641; 17054430 MPLKIP 16002 136647 Trichothiodystrophy 4, nonphotosensitive AR N/A N/A Allergy/Immunology/Infectious; Dental; Dermatologic; Genitourinary; Neurologic; Ophthalmologic Allergy/Immunology/Infectious A number of individuals have been reported with frequent infections, and awareness and prompt and aggressive treatment of infections may be beneficial 4847854; 984047; 2333887; 15645389; 1634754; 16977596; 18603627; 21959366 MPO 7218 4353 Myeloperoxidase deficiency AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Many individuals (including with complete myeloperoxidase deficiency) do not show obvious clinical sequelae, but increased candiasis and incidence of severe infections has been reported in some individuals, and awareness may allow prompt recognition and treatment, which may reduce morbidity and mortality 5796360; 4983030; 4109818; 6260268; 6267975; 6280744; 6321554; 2462938; 7904599; 15507752; 15108282; 17017121; 18453132; 17614858; 17650507; 23228855 MPV17 7224 4358 Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) AR Pediatric Allelic with Charcot-Marie-Tooth neuropathy, axonal, type 2EE (AR) Biochemical; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic Biochemical; Gastrointestinal; Oncologic Glycemic control (eg, with cornstarch) has been shown to slow the progression of hepatic disease; Liver transplanation has been described, though the efficacy is unclear; Awareness of the possible risk of hepatocellular carcinoma may be beneficial 16909392; 16582910; 18695062; 19520594; 19012992; 20074988; 21511859; 22508010; 22593919; 26437932; 30298599 MPZ 7225 4359 Charcot-Marie-Tooth disease, dominant intermediate 3; Charcot-Marie-Tooth disease, axonal, type 2J; Charcot-Marie-Tooth disease, axonal, type 2I; Neuropathy, congenital hypomyelinating 1; Roussy-Levy syndrome; Dejerine-Sottas disease; Charcot-Marie-Tooth disease, demyelinating, type 1B; Hypomyelinating neuropathy, congenital, 2 AD N/A N/A Neurologic General Individuals with biallelic variants have also been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7693129; 8310815; 8664899; 8816708; 9595994; 9537424; 10319895; 10329755; 10071056; 10406984; 10214757; 10553995; 10965800; 11080237; 10764043; 11835375; 14638973; 15159512; 15184631; 15326256; 15642860; 16488608; 16775239; 17663472; 17825553; 21326314; 21280073; 22222859; 22622165; 22633464; 22691094; 22734905 MPZL2 3496 10205 Deafness, autosomal recessive 111 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 29961571; 29982980 MR1 4975 3140 Paroxysmal nonkinesigenic dyskinesia 1 AD N/A N/A Neurologic General Medical treatment (eg, with benzodiazepines) have been described as beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8659518; 9490305; 15496428; 15262732; 15824259; 16216955; 17515540; 19124534; 22967746 MRAP 1304 56246 Glucocorticoid deficiency 2 AR Pediatric Endocrine Endocrine Cortisol treatment can be effective to pevent manifestations such as hypoglycemia or severe sequelae of infectious episodes in infancy/childhood 15654338; 16868047; 20427498; 21951701 MRAP2 21232 112609 Obesity, susceptibility to, 18 AD N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23869016 MRAS 7227 22808 Noonan syndrome 11 AD Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic Cardiovascular Individuals have been described with cardiac disease, inclduing cardiomyopathy as well as structural cardiac anomalies, and awareness may allow early diagnosis and management (surgical management has been described) 28289718; 31173466 MRE11 7230 4361 Breast cancer, susceptibility to AD Adult Allelic with Ataxia-telangiectasia-like disorder 1 (AR) Dermatologic; Neurologic; Oncologic; Ophthalmologic Oncologic Individuals with Ataxia-telangiectasia-like disorder 1 may be at increased risk for malignancy, though the data are unclear Awareness of the risk of malignancy may allow early surveillance, preventive measures, and early diagnosis and treatment of disease 8445618; 8684395; 10612394; 11196167; 11371508; 15269180; 15574463; 17932350; 19383352; 19584272; 19732584; 20087742; 21227757; 21799032; 22006311; 22863007; 24332946; 24549055; 24894818 MRM2 16352 29960 Mitochondrial DAN depletion syndrome 17 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28973171 MRPL12 10378 6182 Combined oxidative phosphorylation deficiency 45 AR N/A N/A Biochemical; Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23603806 MRPL3 10379 11222 Combined oxidative phosphorylation deficiency 9 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21786366 MRPL44 16650 65080 Combined oxidative phosphorylation deficiency 16 AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal Cardiovascular Individuals have been reported as teenagers with hypertrophic cardiomyopathy (as well as with infantile-onset hyptertrophic cardiomyopathy), and surveillance for cardiomyopathy (eg, with echocardiography/electrocardiography) may allow early detection and medical treatment of disease manifestations 23315540 MRPS14 14049 63931 Combined oxidative phosphorylation deficiency 38 AR Pediatric Biochemical; Cardiovascular; Craniofacial; Neurologic Cardiovascular The condition has been described as including features such as hypertrophic cardiomyopathy and arrhythmia, and awareness may allow prompt management of these features 30358850 MRPS16 14048 51021 Combined oxidative phosphorylation deficiency 2 AR N/A N/A Biochemical; Gastrointestinal; Neurologic General The described dysmorphic features may have been coincident (the patient was born to consanguineous parents) as relates to the mitochondrial disorder Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15505824 MRPS2 14495 51116 Combined oxidative phosphorylation deficiency 36 AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29576219 MRPS22 14508 56945 Combined oxidative phosphorylation deficiency 5; Ovarian dysgenesis 7 AR N/A N/A Biochemical; Cardiovascular; Craniofacial; Endocrine; Obstetric; Renal; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17873122; 21189481; 29566152 MRPS23 14509 51649 Combined oxidative phosphorylation deficiency 46 AR N/A N/A Biochemical; Gastrointestinal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26741492 MRPS25 14511 64432 Combined oxidative phosphorylation deficiency 50 AR Pediatric Biochemical; Endocrine; Neurologic Endocrine In addition to other features, an individual has been described as involving adrenal insufficiency requiring hydrocortisone replacement, and awareness may allow early diagnosis and medical management 31039582 MRPS28 14513 28957 Combined oxidative phosphorylation deficiency 47 AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Genitourinary; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30566640 MRPS34 16618 65993 Combined oxidative phosphorylation deficiency 32 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28777931 MRPS7 14499 51081 Combined oxidative phosphorylation deficiency 34 AR Pediatric Audiologic/Otolaryngologic; Biochemical; Endocrine; Neurologic; Renal Audiologic/Otolaryngologic; Endocrine Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with endocrine abnormalities including adrenal failure, and awareness may allow early medical management 25556185 MRTFA 14334 57591 Immunodeficiency 66 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious An individual has been described with severe, early-onset, and recurrent infections, as well as reaction related to BCG vaccine, and and awareness and prompt and aggressive treatment of infections and related sequelae may be beneficial 26224645 MS4A1 7315 931 Immunodeficiency, common variable, 5 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be susceptible to recurrent infections (eg, respiratory infections have been reported), and antiinfectious prophylaxis (including with IVIG therapy) and early and aggressive treatment of infections may be beneficial 20038800 MSH2 7325 4436 Colorectal cancer, hereditary nonpolyposis, type 1 (Lynch syndrome I); Endometrial cancer; Mismatch repair cancer syndrome 2; Muir-Torre syndrome AD/AR Adult (Colorectal cancer, hereditary nonpolyposis, type 1; Endometrial cancer; Muir-Torre syndrome)/Pediatric (Mismatch repair cancer syndrome) Dermatologic; Oncologic Oncologic Homozygous/compound heterozygous variants have been described in individuals with severe disease; Variants in PMS1 thought to be associated with hereditary colon cancer were found to co-segregate in individuals with MSH2 variants; Variants may also contribute to cancer susceptibility, and individuals may be at risk for a number of cancer types In HNPCC, For surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types (individuals may be at risk for a number of cancer types), awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; Individuals with Mismatch repair cancer syndrome are at risk of multiple types of malignancy, and awareness may allow early detection and management 6020987; 5684233; 4016686; 2029018; 8484121; 8252616; 8261515; 8484120; 8072530; 8931714; 9218993; 9593786; 9634524; 9843200; 10534628; 10190329; 10196371; 11600610; 11112663; 11809679; 12549480; 12650804; 14574010; 14994245; 15520370; 14871915; 15235030; 15872208; 15662714; 15937084; 16807412; 16372347; 16511680; 17539897; 17327285; 19419416; 20093870; 20301390; 20591884; 23612316; 23729658; 23891921; 23990280; 24434690 MSH3 7326 4437 Endometrial carcinoma AD Adult Oncologic Oncologic Individuals may be at risk for a number of types of cancer In HNPCC, for surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types (individuals may be at risk for a number of cancer types), awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; Individuals with Mismatch repair cancer syndrome are at risk of multiple types of malignancy, and awareness may allow early detection and management 9354786; 12732731; 15098177; 15340263; 16000562; 16283678; 17557300; 24434690 MSH5 7328 4439 Premature ovarian failure 13 AR Pediatric Endocrine; Obstetric Obstetric Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency 28175301 MSH6 7329 2956 Colorectal cancer, hereditary nonpolyposis type 5; Mismatch repair cancer syndrome 3; Endometrial cancer AD/AR Adult (Colorectal cancer, hereditary nonpolyposis type 5; Endometrial cancer)/Pediatric (Mismatch repair cancer syndrome) Oncologic Oncologic Individuals may be at risk for additional types of malignancy In HNPCC, for surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types, awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; Individuals with Mismatch repair cancer syndrome are at risk of multiple types of malignancy, and awareness may allow early detection and management 9354786; 12732731; 15098177; 15340263; 16000562; 16283678; 17557300; 29345684 MSL3 7370 10943 Basilicata-Akhtar syndrome XL N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30224647 MSMO1 10545 6307 Microcephaly, congenital cataract, and psoriasiform dermatitis AR Pediatric Allergy/Immunology/Infectious; Biochemical; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic Allergy/Immunology/Infectious; Biochemical; Dermatologic Medical management (with oral and topical cholesterol and statin supplements,) has been described as beneficial in terms of laboratory (eg, immunocyte profiles) and clinical parameters (eg, growth, arthralgias, skin disease) 21285510; 24144731 MSN 7373 4478 Immunodeficiency 50 XL Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described with early onset and recurrent bacterial or varicella zoster virus infections, and awareness may allow preventive measures and early and aggressive treatments of infections 27405666 MSR1 7376 4481 Barrett esophagus/esophageal adenocarcinoma; Prostate cancer AD Adult Gastrointestinal; Oncologic Gastrointestinal; Oncologic While some (eg, common) variants may increase the risk of prostate cancer slightly, others appear to confer much higher risk Awareness of disease risk may allow surveillance, preventive measures (eg, related to Barrett esophagus) and early treatment of malignancy, which may reduce morbidity and mortality 11443539; 12244320; 12839931; 12958598; 15536476; 16287155; 17768178; 17903305; 18398045; 20086112; 21791690 MSRB3 27375 253827 Deafness, autosomal recessive 74 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 19650862; 21185009 MSTN 4223 2660 Muscle hypertrophy AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15215484 MSTO1 29678 55154 Myopathy, mitochondrial, and ataxia AD/AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28544275; 28554942 MSX1 7391 4487 Orofacial cleft 5; Tooth agenesis, selective, 1, with/without orofacial cleft; Witkop syndrome AD N/A N/A Craniofacial; Dental; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8696335; 10742093; 11369996; 12097313; 12807959; 15264286; 15354328; 16327884; 16498076; 16868654; 16932841; 18374898; 19346736; 21297014; 21626677; 22297032 MSX2 7392 4488 Craniosynostosis 2; Parietal foramina with cleidocranial dysplasia; Parietal foramina 1 AD N/A N/A Craniofacial; Musculoskeletal General Upstream microduplications have been described as causing Cleidocranial dysplasia Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8106171; 8357019; 10742103; 14571277; 16222674; 16319823; 16642368; 17955513; 18000908; 19533795; 21082653 MT-ATP6 7414 4508 Myopathy, lactic acidosis, and sideroblastic anemia 3 Maternal N/A Allelic with Neuropathy, ataxia, and retinitis pigmentosa (Maternal); Leber hereditary optic neuropathy (Maternal); Ataxia and polyneuropathy, adult-onset (Maternal); Cardiomyopathy, infantile hypertrophic (Maternal); Leigh syndrome (Maternal); Striatonigral degeneration, infantile, mitochondrial (Maternal); Mitochondrial complex V (ATP synthase) deficiency mitochondrial type 1 (Maternal) Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular; Hematologic In many of the allelic disorders, mtochondrial variants may involve a variety of sequelae, including cardiovascular manifestations such as cardiomyopathy Among other manifestations, the conditions can involve transfusion-dependent anemia, and awareness may allow early management; Surveillance for cardiovascular manifestations may allow early medical interventions 2137962; 1436530; 1550128; 8095070; 8250532; 8042671; 8554662; 7726182; 7668837; 8739943; 9199572; 9329425; 9501263; 9631394; 9556461; 10417290; 10590437; 10604142; 10676807; 11245730; 11730668; 11843698; 17452590; 19124644; 19188198; 22231385; 22577227; 22773856; 25037980 MT-ATP8 7415 4509 Brain pseudoatrophy, reversible, valproate-induced, susceptibility to Maternal Pediatric Allelic with Cardiomyopathy, apical hypertrophic, and neuropathy (Maternal); Cardiomyopathy, infantile hypertrophic Biochemical; Cardiovascular; Neurologic Pharmacogenomic Variants can also be associated with a range of typical mitochondrial-related phenotypes, including cardiac manifestations such as cardiomyopathy Medication selection would be impacted in individuals with variants 17101920; 17954552; 19188198 MT-CO1 7419 4512 Deafness, mitochondrial Maternal Pediatric Allelic with Myoglobinuria, recurrent (maternal); Leber hereditary optic neuropathy (maternal); Sideroblastic anemia (maternal); Cytochrome C oxidase deficiency (maternal) Audiologic/Otolaryngologic; Biochemical; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal Audiologic/Otolaryngologic; Pharmacogenomic In some individuals, aminoglycoside administration can result in deafness; Cosegregation with other variants may result in disease Mitochondrial variants may involve a variety of sequelae, including hearing impairment, with highly variable age of onset, and for individuals with early-onset hearing impairment, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Aminoglycosides should be avoided 1634041; 10577941; 10980727; 12140182 MT-CO2 7421 4513 Cytochrome c oxidase deficiency Maternal N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10205264 MT-CO3 7422 4514 Myoglobinuria, recurrent Maternal N/A Allelic with Cytochrome c oxidase deficiency (Maternal); Leber hereditary optic neuropathy (Maternal) Biochemical; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8240356; 8630495; 10788526; 11063732 MT-ND1 7455 4535 Deafness, mitochondrial Maternal Pediatric Allelic with Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (Maternal); Leber hereditary optic neuropathy (Maternal); Leber optic atrophy and dystonia (Maternal) Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic Audiologic/Otolaryngologic As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Mitochondrial variants may involve a variety of sequelae, including hearing impairment, with highly variable age of onset, and for individuals with early-onset hearing impairment, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 1928099; 2018041; 1674640; 1732158; 10519336; 15466014; 15505787; 17562939; 18216301; 21625124; 21723259; 21968326; 22079202; 22241583; 22577081 MT-ND2 7456 4536 Leber hereditary optic neuropathy; Mitochondrial complex I deficiency Maternal N/A N/A Biochemical; Musculoskeletal; Neurologic; Ophthalmologic General Mitochondrial variants may involve a variety of sequelae, including hearing impairment Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1732158; 20454697; 21145289 MT-ND3 7458 4537 Leber optic atrophy and dystonia; Mitochondrial complex I deficiency, mitochondrial type 1 Maternal N/A N/A Biochemical; Neurologic; Ophthalmologic General Mitochondrial variants may involve a variety of sequelae, including hearing impairment Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14705112; 19458970 MT-ND4 7459 4538 Leber hereditary optic neuropathy; Leber optic atrophy and dystonia; Mitochondrial complex I deficiency Maternal N/A N/A Biochemical; Musculoskeletal; Neurologic; Ophthalmologic General Mitochondrial variants may involve a variety of sequelae, including hearing impairment; Variants in genes such as PRICKLE3 may modify the condition Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 201231; 2566116; 1763894; 2039048; 8644732; 18216301; 32516135 MT-ND4L 7460 4539 Leber hereditary optic neuropathy Maternal N/A N/A Biochemical; Ophthalmologic General Mitochondrial variants may involve a variety of sequelae, including hearing impairment Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11935318 MT-ND5 7461 4540 Myoclonic epilepsy with ragged red fibers; Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; Leber hereditary optic neuropathy; Mitochondrial complex I deficiency Maternal N/A N/A Biochemical; Musculoskeletal; Neurologic; Ophthalmologic General Mitochondrial variants may involve a variety of sequelae, including hearing impairment Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1900003; 1732158; 8213825; 8016139; 18524835 MT-ND6 7462 4541 Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; Oncocytoma; Leber hereditary optic neuropathy; Leber optic atrophy and dystonia; Mitochondrial complex I deficiency Maternal N/A N/A Biochemical; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Mitochondrial variants may involve a variety of sequelae, including hearing impairment Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3736869; 1417830; 8016139; 8644732; 11781695; 14735585; 16380132; 18524835; 21555623 MT-RNR1 7470 4549 Deafness, mitochondrial Maternal Pediatric Audiologic/Otolaryngologic; Biochemical; Cardiovascular Audiologic/Otolaryngologic; Pharmacogenomic In some individuals, aminoglycoside administration can result in deafness; Individuals have also been reported with cardiomyopathy Mitochondrial variants may involve a variety of sequelae, including hearing impairment, with highly variable age of onset, and for individuals with early-onset hearing impairment, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Aminoglycosides should be avoided 7689389; 9039999; 9887373; 9490575; 10326749; 10577941; 9915970; 10521300; 10788333; 11079536; 11313749; 12372057; 12920080; 12624722; 15286157; 14755216; 14681830; 15555598; 15637703; 15708009; 16380089; 16458854; 16631122; 16375862; 16782057; 17341440; 18261986; 18983818 MT-RNR2 7471 4550 Chloramphenicol toxicity/resistance Maternal Pediatric General Pharmacogenomic Medication selection would be impacted in individuals with variants; Sensitivity to streptomycin has been suggested as well 14233236; 5785754; 6273808; 7219548 MT-TC 7477 4511 Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes Maternal N/A N/A Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic General Mitochondrial variants may involve a variety of sequelae, including hearing impairment Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8829635; 9185178; 17241783; 17724295; 18386806; 18800376 MT-TE 7479 4556 Diabetes-deafness syndrome; Mitochondrial myopathy, infantile, transient; Mitochondrial myopathy with diabetes Maternal N/A N/A Audiologic/Otolaryngologic; Biochemical; Craniofacial; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic General Mitochondrial variants may involve a variety of sequelae, including hearing impairment Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4114165; 7726154; 9353617; 15048886; 19720722; 21194154; 21931168 MT-TF 7481 4558 Myoclonic epilepsy with ragged red fibers; Nephropathy, tubulointerstitial; Encephalopathy, mitochondrial; Epilepsy, mitochondrial; Myopathy, mitochondrial; Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes Maternal N/A N/A Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Renal General Mitochondrial variants may involve a variety of sequelae, including hearing impairment; As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15184630 MT-TL1 7490 4567 Brain pseudoatrophy, reversible, valproate-induced, susceptibility to Maternal Pediatric Allelic with Cytochrome c oxidase deficiency (Maternal); Myoclonic epilepsy with ragged red fibers (Maternal); Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (Maternal); Diabetes-deafness syndrome (Maternal); Cyclic vomiting syndrome (Maternal); SIDS, susceptibility to (Maternal) Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic; Renal General; Pharmacogenomic Mitochondrial variants may involve a variety of sequelae, including hearing impairment; As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection In Brain pseudoatrophy, reversible, valproate-induced, susceptibility to, variants may have pharmacogenomic importance, as medication selection would be impacted in individuals with variants 1514779; 1360090; 8254046; 9243242; 9506761; 10482110; 10519336; 10699170; 11708999; 12905015; 15466014; 16326995; 16476929; 17101920 MT-TS1 7497 4574 Deafness, nonsyndromic sensorineural, mitochondrial Maternal Pediatric Allelic with Myoclonic epilepsy with ragged red fibers (maternal); Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (maternal) Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic Audiologic/Otolaryngologic; Pharmacogenomic In some individuals, aminoglycoside administration can result in deafness Mitochondrial variants may involve a variety of sequelae, including hearing impairment, with highly variable age of onset, and for individuals with early-onset hearing impairment, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Aminoglycosides should be avoided 8019558; 10340654; 10371545; 11175301 MT-TV 7500 4577 Charcot-Marie-Tooth disease, axonal, mitochondrial form, 1 Maternal N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32715519 MTAP 7413 4507 Diaphyseal medullary stenosis with malignant fibrous histiocytoma AD Pediatric Musculoskeletal; Oncologic Oncologic Individuals are at high risk for aggressive bone sarcoma, and surveillance and early treatment may be beneficial to reduce morbidity and mortality 4713573; 3745248; 8680521; 8781110; 16244874; 22464254 MTFMT 29666 123263 Combined oxidative phosphorylation deficiency 15 AR Pediatric Allelic with Mitochondrial complex I deficiency, nuclear type 27 (AR) Biochemical; Cardiovascular; Neurologic; Ophthalmologic Cardiovascular Among other multi-systemic manifestations, the condition may include cardiac manifestations such as Wolff-Parkinson-White syndrome, and surveillance may allow early diagnosis and management 21907147; 22499348; 23499752; 24461907 MTHFD1 7432 4522 Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Hematologic; Neurologic; Renal Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical Individuals have been described as presenting with severe and recurrent infections, as well as other sequelae, such as renal disease, and medical management (with folate and hydroxycobalamin) has been described as beneficial; In addition to folate and hydroxycobalamin treatment, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Related to hearing deificits, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 23296427; 25633902; 27707659 MTHFR 7436 4524 Homocystinuria due to MTHFR deficiency AR Pediatric Biochemical; Cardiovascular; Hematologic; Neurologic Biochemical; Cardiovascular; Hematologic Variants in MTHFR may interact with variants in other genes, such as F5 to result in susceptibility to hematologic manifestations Medical therapy (eg, with folate, betaine, riboflavin, hydroxycobalamin) can be effective; In individuals with heterozygous variants, there may be an increased risk of thrombophilia, and considerations may be warranted in certain situations 3889647; 1998339; 1866027; 1627352; 8456826; 7920641; 7647779; 7726158; 7564788; 8691945; 8826441; 8892013; 8940272; 8994411; 9133512; 9341863; 9244205; 9372726; 9068801; 9878639; 10323741; 10384377; 10536004; 10679944; 10862840; 10923034; 10961793; 11508552; 11170082; 11274424; 11938441; 12142069; 12673793; 15896655; 15979034; 16145688; 16216822; 17409006; 18658082; 18708589; 19697151; 20236116; 20356773; 20850942; 22578003; 22646290; 22665071; 22721898; 22773907; 22807619; 22856671; 22947400; 23124942 MTHFS 7437 10588 Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination AR Pediatric Biochemical; Neurologic Neurologic Individuals have been described with refractory seizures and recurrent episodes of hyperthermia, which responded to lamotrigine; A combination of oral L-5-methyltetrahydrofolate and intramuscular methylcobalamin has been described as resulting in mild functional improvements 30031689 MTM1 7448 4534 Myopathy, centronuclear, X-linked XL Pediatric Gastrointestinal; Hematologic; Musculoskeletal; Renal Hematologic Increased risk of findings including subdural hemorrhage, subdural hygromas, and cephalohematomas has been reported Among other findings affecting multiple organ systems, individuals may demonstrate a vitamin-K respondent bleeding diathesis, and surveillance and treatment may be beneficial 5816884; 8640223; 9285787; 9169146; 9305655; 10726846; 9450905; 9931531; 10502779; 10323249; 10714588; 10790201; 11552027; 12707446; 15883335; 15690409; 19197364; 20434914; 20500434; 21881007; 22101172; 22153990; 22258523; 22264517; 22520358 MTMR2 7450 8898 Charcot-Marie-Tooth disease, type 4B1 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10802647 MTO1 19261 25821 Combined oxidative phosphorylation deficiency 10 AR Pediatric Biochemical; Cardiovascular; Neurologic Biochemical Biochemical treatments (eg, with a "mitochondrial cocktail") and ketogenic diet have been described, but the efficacy has been reported as unclear The condition can include findings such as hypertrophic cardiomyopathy, hypoglycemia, and and lactic acidosis; Treatment with biotin, coenzyme Q10, thiamine, and dichloroacetate has been reported as beneficial in multiple individuals 22608499; 23929671; 29331171 MTOR 3942 2475 Smith-Kingsmore syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25851998; 26542245; 27753196; 27830187 MTPAP 25532 55149 Spastic ataxia 4, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20970105; 25008111 MTR 7468 4548 Homocystinuria-megaloblastic anemia, cblG complementation type AR Pediatric Biochemical; Cardiovascular; Hematologic; Neurologic; Renal Biochemical Medical treatment may be beneficial (while hydroxycobalamin may not be as effective as in other MMA types, other treatments, such as betaine, methylfolate, and even methionine supplements may be attempted) 2897628; 2203337; 8968736; 8968737; 12068375; 20301503; 22108709 MTRR 7473 4552 Homocystinuria-megaloblastic anemia, cobalamin E complementation type AR Pediatric Biochemical; Hematologic; Neurologic; Renal Biochemical Treatment (eg, with hydroxycobalamin, folate, methylcobalamin) has been reported as effective 6700644; 2860337; 3812589; 9427140; 10444342; 15060097; 15979034; 15714522 MTTP 7467 4547 Abetalipoproteinemia AR Pediatric Gastrointestinal; Hematologic; Neurologic; Ophthalmologic Gastrointestinal Dietary measures (eg, with a low fat diet and supplementation of essential fatty acids and fat-soluble vitamins) can be beneficial, and early initiation can prevent/decrease severe sequelae 15411425; 14925152; 13745738; 14237436; 4135110; 848999; 716878; 7425890; 6959555; 2339706; 1439810; 8361539; 9686820; 17275380; 18239027; 18611256; 20402070; 21333248; 21394827; 21502686; 23090820; 23556456; 24288038 MTX2 7506 10651 Mandibuloacral dysplasia progeroid syndrome AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Cardiovascular Among other findings, individuals may have early-onset respiratory infections, and awareness may allow prompt diagnosis and management; Cardiovascular manifestations, including cardiomyopathy and valvular anomalies, have been described, and awareness may allow prompt diagnosis and management 32917887 MUC1 7508 4582 Tubulointerstitial kidney disease, autosomal dominant, 2 AD N/A N/A Renal General Renal transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15384011; 23396133 MUSK 7525 4593 Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency AR Pediatric Allelic with Fetal akinesia deformation sequence 1 (AR) Musculoskeletal; Neurologic Musculoskeletal; Neurologic; Pharmacogenomic Allelic with Fetal akinesia deformation sequence 2 (AR) likely represents an extreme phenotype of Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency Most individuals with Myasthenic syndrome, congenital benefit from AChE inhibitors and/or potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; Some individuals are treated with quinidine, which has some major side effects and may be detrimental in individuals with AChR deficiency 1783919; 8041349; 9120223; 8819551; 9546329; 12771277; 15496425; 15951177; 20301347; 25537362; 25612909 MUTYH 7527 4595 Familial adenomatous polyposis, 2; Colorectal adenomatous polyposis, autosomal recessive, with pilomatricomas AR Adult Dermatologic; Oncologic Oncologic Variants may also be inolved in susceptibility to other types of malignancies Individuals may present with colonic neoplasia, and regular surveillance for neoplasms may allow early treatment of tumors, which may improve outcomes; In some individuals, additional surgical measures such as total colectomy with ileorectal anastomosis, may be indicated in addition to surveillance for neoplasms; In addition to colorectal neoplasms, individuals are at high risk for a number of other cancer types (including breast cancer), and awareness may allow early diagnosis and treatment 11818965; 12393807; 12853198; 12606733; 15690400; 21061173; 21063410; 21171015; 21696383; 22371070; 22658618; 22744763; 22851115; 22865608 MVD 7529 4597 Porokeratosis 7, multiple types AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22983302 MVK 7530 4598 Mevalonic aciduria; Hyper-IgD syndrome AR Pediatric Allelic with Porokeratosis 3, multiple types (AD) Allergy/Immunology/Infectious; Dermatologic; Biochemical; Gastrointestinal Allergy/Immunology/Infectious In Mevalonic aciduria, diagnosis can be challenging, and effective treatment is available with specific agents (eg, steroids, leukotriene receptor antagonists); In Hyper-IgD syndrome, accurate diagnosis may be beneficial in order to avoid unnecessary surgery for suspected appendicitis/acute abdomen; Medical treatment (eg, corticosteroids, leukotriene receptor inhibitors) during the acute phase can be effective, as well as medical treatment in the non-acute phase 6144826; 3012338; 8386351; 8190036; 8973873; 10369262; 10369261; 11313769; 11742050; 15149516; 15457465; 15536479; 16835861; 18409191; 20194276; 21399979; 21548022; 22159817; 22246419; 22271696; 22983302 MYBPC1 7549 4604 Arthrogryposis, distal, type 1B; Myopathy, congenital, with tremor; Lethal congenital contractural syndrome 4 AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20045868; 22610851; 31025394; 31264822 MYBPC3 7551 4607 Cardiomyopathy, familial hypertrophic, 4; Cardiomyopathy, dilated, 1MM; Left ventricular noncompaction 10 AD/AR Pediatric Cardiovascular Cardiovascular Surveillance in order to allow early diagnosis and treatment of cardiomyopathy can be beneficial; Cardiac transplantation has been described 7493026; 7493025; 9241277; 9562578; 10424815; 12788380; 15519027; 16199542; 16679492; 17655857; 17937428; 18337725; 19858127; 21839045; 22021246; 22314326; 22455086 MYCN 7559 4613 Feingold syndrome 1 AD N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Renal General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9096752; 14518066; 15821734; 16906565; 18671284; 18470948; 19852433; 20301770; 21224895; 22842076 MYD88 7562 4615 Immunodeficiency 68 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been reported as being susceptible to severe and recurrent pyogenic bacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 18669862; 21057262; 21734245 MYF5 7565 4617 Ophthalmoplegia, external, with rib and vertebral anomalies AR N/A N/A Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29887215 MYF6 7566 4618 Myopathy, centronuclear, 3 AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11053684 MYH11 7569 4629 Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 AD/AR Pediatric Cardiovascular; Gastrointestinal; Genitourinary; Renal Cardiovascular; Gastrointestinal; Renal In Aortic aneurysm, familial thoracic 4, surveillance for aortic aneurysms and related anomalies (as well as PDA) can allow early detection and treatment, potentially decreasing morbidity and mortality; In Visceral myopathy 2, individuals have been described with a variety of gastrointestinal sequelae, some of which may benefit from medical and/or surgical interventions; Individuals with Megacystis-microcolon-intestinal hypoperistalsis syndrome may have anomalies such as intestinal and genitorenal anomalies, and awareness may allow prompt surgical and medical management 11249915; 14722581; 16444274; 17666408; 22415348; 22968129; 25407000; 29575632; 31389005; 31427716; 31944481 MYH14 23212 79784 Deafness, autosomal dominant 4; Deafness, autosomal dominant 4B; Peripheral neuropathy, myopathy, hoarseness, and hearing loss AD N/A N/A Audiologic/Otolaryngologic; Musculoskeletal; Neurologic General The onset of deafness has been described as postlingual Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7655461; 11938438; 15015131; 16222661; 21480433; 21368133 MYH2 7572 4620 Myopathy, proximal, with ophthalmoplegia AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11114175; 24193343 MYH3 7573 4621 Arthrogryposis, distal, type 2A; Arthyrgryposis, distal, type 2B3; Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A; Contractures, pterygia, and variable skeletal fusions syndrome 1B AD N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21032118; 4975238; 5467037; 4220006; 7039311; 2803721; 9138511; 4220006; 16510655; 16642020; 18695058; 19309503; 19571066; 19684571; 20924721; 21531865; 25957469; 29625835; 29805041 MYH6 7576 4624 Cardiomyopathy, dilated, 1EE; Cardiomyopathy, familial hypertrophic 14 AD Pediatric Allelic with Atrial septal defect 3 (AD) Cardiovascular Cardiovascular Permanent cardiac pacing is the only effective treatment for symptomatic/irreversible sinus node dysfunction; Sick sinus syndrome is the most common indication for permanent pacemaker implantation 11815426; 15998695; 15735645; 21378987; 22194935 MYH7 7577 4625 Cardiomyopathy, dilated, 1S; Cardiomyopathy, familial hypertrophic 1; Myopathy, distal; Myopathy, myosin storage, autosomal recessive AD/AR Pediatric Allelic with Myopathy, myosin storage, autosomal dominant (AD); Myopathy, scapuloperoneal (AD); Myopathy, distal, 1 (Laing distal myopathy) (AD) Cardiovascular; Musculoskeletal Cardiovascular Compound heterozygosity and digenic inheritance (with MYLK2) has been described as an explanation for severe manifestations in some individuals Individuals can have cardiovascular anomalies, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmias, and surveillance and early treatment may be beneficial 13732753; 4104682; 1975517; 1361491; 1552912; 8254035; 8483915; 8343162; 8282798; 7909436; 8655135; 9544842; 10521296; 10424815; 11106718; 11102913; 11424919; 11733062; 11166161; 12379228; 14663035; 12975303; 12749056; 14520662; 14659406; 15136674; 15322983; 16267253; 15483641; 15699387; 16684601; 16650083; 17372140; 17548557; 17476457; 17336526; 18175163; 18506004; 19026577; 19138847; 19336582; 20503496; 20733148; 21395566; 21896538; 23117287; 23478172; 23956225; 25666907 MYH8 7578 4626 Carney complex variant; Arthrogryposis, distal, type 7 (Trismus-pseudocamptodactyly syndrome) AD N/A N/A Craniofacial; Musculoskeletal General In one family, cardiac and dermatologic findings appeared to co-segregate with the disease Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4443857; 4837286; 12800911; 15590965; 15282353; 17041932; 18049072; 20949528 MYH9 7579 4627 Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss AD Pediatric Allelic with Deafness, autosomal dominant 17 (AD) Audiologic/Otolaryngologic; Hematologic; Ophthalmologic; Renal Hematologic In active hemorrhage, DDAVP may decrease bleeding time; otherwise, platelet transfusion is necessary; Precautions related to bleeding risk may be beneficial 13940543; 1449176; 5011389; 2981587; 3232700; 2851314; 2176899; 1396928; 1319112; 8280620; 9390828; 9915977;10973260; 10973259; 11590545; 12533692; 12621333; 12792306; 15613099; 15667538; 16969870; 17241369; 18059020; 18284620; 19208103; 19285578; 19450438; 19860543; 20002731; 20174760; 20221761; 20301740; 20601875; 22541678; 23123319 MYL1 7582 4632 Myopathy, congenital, with fast-twitch (type II) fiber atrophy AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30215711 MYL2 7583 4633 Cardiomyopathy, familial hypertrophic, 10 AD Pediatric Allelic with Infantile type I muscle fibre disease and cardiomyopathy (AR) Cardiovascular; Musculoskeletal Cardiovascular Medical/surgical (ICD) management may ameliorate/prevent severe sequelae 8673105; 9535554; 12404107; 21896538; 23365102 MYL3 7584 4634 Cardiomyopathy, familial hypertrophic, 8 AD/AR Pediatric Cardiovascular Cardiovascular Early recognition may allow preventive measures and early medical management, which may ameliorate severe sequelae 6211078; 8673105; 12021217; 16267253; 21239446; 21896538 MYL4 7585 4635 Atrial fibrillation, familial, 18 AD Pediatric Cardiovascular Cardiovascular Although only affected adults have been described, earlier surveillance is anticipated to reveal sequelae in children with variants The condition involves conduction disease with atrial fibrillation and reduced left atrial function, and early recognition may allow preventive measures and early medical and surgical management, which may ameliorate severe sequelae 25807286; 27066836 MYLK 7590 4638 Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 AD/AR Pediatric Cardiovascular; Gastrointestinal; Renal Cardiovascular; Gastrointestinal; Renal In Aortic aneurysm, familial thoracic, preventive measures and medical management may be helpful to help decrease morbidity; Individuals with Megacystis-microcolon-intestinal hypoperistalsis syndrome may have intestinal anomalies and hydronephrosis, and awareness may allow prompt surgical and medical management 21055718; 20301299; 28602422 MYLK2 16243 85366 Cardiomyopathy, hypertrophic AD/Digenic Pediatric Cardiovascular Cardiovascular Digenic inheritance (with MYH7) has been described Surveillance for cardiomyopathy (eg, with echocardiography/electrocardiography) and early medical treatment may reduce morbidity 11733062 MYLPF 29824 29895 Arthrogryposis, distal, type 1C AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32707087 MYMK 33778 389827 Carey-Fineman-Ziter syndrome AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28681861; 29560417 MYO15A 7594 51168 Deafness, autosomal recessive 3 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 17851452; 23226338 MYO18B 18150 84700 Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25748484 MYO1A 7595 4640 Deafness, autosomal dominant 48 AD Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic The condition has variable age of onset and severity Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12596055; 12736868 MYO1E 7599 4643 Focal segmental glomerulosclerosis 6 AR Pediatric Renal Renal The condition can involve early-onset renal disease, and awareness may allow prompt diagnosis and management (eg, glucocorticoid and cyclosporine use has been descvribed as beneficial); Renal transplant has been described 21756023 MYO3A 7601 53904 Deafness, autosomal recessive 30 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12032315 MYO5A 7602 4644 Griscelli syndrome, type 1 AR N/A N/A Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9207796; 10704277; 12452176 MYO5B 7603 4645 Diarrhea 2, with microvillus atrophy AR Pediatric Gastrointestinal; Renal Gastrointestinal; Renal Individuals may require nutritional support with parenteral nutrition; Renal fanconi syndrome has been described, and appropriate care of related sequelae may be beneficial 16800870; 19006234; 18724368; 21199752; 20186687; 22030065; 21206382; 22441677 MYO6 7605 4646 Deafness, autosomal recessive 37 AR Pediatric Allelic with Deafness, autosomal dominant, 22 (AD), which has later onset Audiologic/Otolaryngologic Audiologic/Otolaryngologic One kindred has been described also segregating hypertrophic cardiomyopathy with the MYO6 variant, but the overall evidence appears mixed as relates to cardiac findings Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 11468689; 12687499; 15060111; 18212818; 18348273; 19893302; 28000701; 29044474; 29224747 MYO7A 7606 4647 Deafness, autosomal recessive 2; Usher syndrome, type I AR Pediatric Allellic with Deafness, autosomal dominant 11 (AD) Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic The timing of onset has been reported as highly variable, though heterozygous variants appear to result in postlingual onset Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 7951250; 8776602; 9171832; 7870171; 9171833; 11391666; 11889386; 15221449; 18181211; 20132242; 21436283; 21150918; 23226338 MYO9A 7608 4649 Myasthenic syndrome, congenital, 24, presynaptic AR Pediatric Musculoskeletal; Neurologic Musculoskeletal; Neurologic Individuals have been described as benefiting from medical management (with pyridostigmine and 3,4-DAP) 26752647; 27259756 MYOC 7610 4653 Glaucoma 1, open angle, A AD/AR/Digenic Pediatric Ophthalmologic Ophthalmologic; Pharmacogenomic Digenic inheritance (with CYP1B1) has been reported Early diagnosis and treatment may be effective to decrease morbidity and mortality related to vision loss; Agents that may contribute to glaucoma should be avoided 8513321; 9005853; 9535666; 10330365; 11535458; 11709019; 11774072; 15025728; 15108121; 15733270; 17562996; 17197538; 17499207 MYOCD 16067 93649 Megabladder, congenital AD N/A N/A Genitourinary; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31513549 MYOD1 7611 4654 Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies AR N/A N/A Craniofacial; Musculoskeletal; Pulmonary; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26733463; 30403323; 31260566 MYORG 19918 57462 Basal ganglia calcification, idiopathic, 7, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29910000; 30460687; 30656188; 30649222 MYOT 12399 9499 Myopathy, myofibrillar, 3 AD Pediatric Allelic with Muscular dystrophy, limb-girdle, 1A (AD); Myopathy, spheroid body (AD) Cardiovascular; Musculoskeletal; Neurologic Cardiovascular Individuals typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD, as well as medical treatment with ACE inhibitors and/or beta-blockers); Cardiac transplantation may be necessary in individuals with severe forms of cardiomyopathy 571956; 3275904; 9270668; 10958653; 12428213; 15111675; 16380616; 20301672; 21336781; 21676617 MYOZ2 1330 51778 Cardiomyopathy, familial hypertrophic, 16 AD Pediatric Cardiovascular Cardiovascular Surveillance and preventive measures related to cardiac manifestations, which have been reported as including arrhythmias, may allow early diagnosis and medical management as well as pacemaker placement, which may reduce morbidity and mortality 17347475; 19472918 MYPN 23246 84665 Cardiomyopathy, dilated, 1KK; Cardiomyopathy, familial hypertrophic, 22; Cardiomyopathy, familial restrictive, 4 AD Pediatric Allelic with Nemaline myopathy 11, autosomal recessive Cardiovascular; Neurologic Cardiovascular Surveillance (eg, including echocardiogram and electrocardiogram) and preventive measures related to cardiac manifestations may allow early diagnosis and management, which may reduce morbidity and mortality 18006477; 22286171; 22892539; 28017374 MYRF 1181 745 Encephalitis/encephalopathy, mild, with reversible myelin vacuolization AD Pediatric Allelic with Cardiac-Urogenital syndrome (AD) Cardiovascular; Gastrointestinal; Genitourinary; Neurologic; Pulmonary Neurologic The condition, which involves acute reversible encephalopathy in children, and is frequently associated with a trigger, such as a febrile illness, has been reported as being treatable with steroids 29265453; 29446546; 30070761; 30532227 MYT1L 7623 23040 Mental retardation, autosomal dominant 39 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21990140; 23033978; 23160955; 25232846; 26240977; 30055078 NAA10 18704 8260 Ogden syndrome XL Pediatric Allelic with Microphthalmia, syndromic 1 (Lenz microphthalmia) (XL) Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal Cardiovascular Though the overall phenotype may be recognizable, reported individuals have died due to sequelae of arrhythmias, and surveillance and awareness may allow early diagnosis and treatment, which may reduce morbidity and mortality 11426460; 21700266; 24431331; 25099252; 26522270 NAA15 30782 80155 Mental retardation, autosomal dominant, 50 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28191889 NACC1 20967 112939 Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination (NECFM) AD N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28132692 NADK2 26404 133686 2,4-dienoyl-CoA reductase deficiency AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24847004 NADSYN1 29832 55191 Vertebral, cardiac, renal, and limb defects syndrome 3 AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Pulmonary; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31883644 NAGA 7631 4668 Kanzaki disease; Alpha-n-acetylgalactosaminidase deficiency; Schindler disease type I; Schindler disease type III AR N/A N/A Biochemical; Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2564952; 2243144; 7707696; 8071745; 8040340; 8782044; 11313741; 11251574; 14685826; 15619430 NAGLU 7632 4669 Mucopolysaccharidosis type IIIB (Sanfilippo syndrome B) AR N/A Allelic with Charcot-Marie-Tooth disease, axonal, type 2V (AD) Biochemical; Musculoskeletal; Neurologic General BMT has been reported as beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4261742; 3118713; 1606713; 1293388; 8650226; 3118713; 11068184; 12202988; 15933803; 18218046; 20852935; 21937992; 21712855; 22976768; 25818867 NAGS 17996 162417 N-acetylglutamate synthase deficiency AR Pediatric Biochemical; Neurologic Biochemical The condition may manifest with severe neurological sequelae secondary to the accumulation of ammonia, and medical treatment both in the acute and chronic setting (eg, with N-carabamylglutamate) can be effective 7453791; 3139931; 2373115; 1405478; 7623444; 9877039; 10626533; 12594532; 17421020; 17510757; 19533169; 20301396; 21941437; 22594780; 23776373; 25135652 NALCN 19082 259232 Congenital contractures of the limbs and face, hypotonia, and developmental delay; Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 AD/AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12558119; 23749988; 25683120 NANOS1 23044 340719 Spermatogenic failure 12 AD N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23315541 NANS 19237 54187 Spondyloepimetaphyseal dysplasiam Genevieve type AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27213289 NARS1 7643 4677 Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities AD/AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32738225; 32788587 NARS2 26274 79731 Deafness, autosomal recessive 94 AR Pediatric Allelic with Combined oxidative phosphorylation deficiency 24 (AR) Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic Audiologic/Otolaryngologic Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25385316; 25629079; 25807530 NAT1 7645 9 Acetylation, NAT1-related AD Pediatric Biochemical Pharmacogenomic Medication dosage/selection may be affected related to multiple agents, including isoniazid, hydralazine, phenytoin, procainamide, and some sulfa drugs 17909564; 21878835 NAT2 7646 10 Acetylation, NAT2-related AD Pediatric Biochemical Pharmacogenomic Variants may have pharmacogenomic importance, as medication dosage/selection may be affected related to multiple agents, including isoniazid, hydralazine, phenytoin, procainamide, and some sulfa drugs 13820968; 14164493; 5414058; 871863; 913027; 7378086; 3707628; 3712391; 3778197; 3815349; 1968463; 2068113; 8102597; 7920692; 7668286; 8637343; 9918135; 9660060; 12654968; 16416399; 19379125; 19891553; 20485159; 20602614; 20860460; 20941486; 22092036 NAT8L 26742 339983 N-acetylaspartate deficiency AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11310630; 15328569; 16802720; 19807691 NAXD 25576 55739 Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 AR Pediatric Allergy/Immunology/Infectious; Hematologic; Neurologic Allergy/Immunology/Infectious In addition to severe neurologic features, individuals have been described with skin lesions consistent with epidermal necrosis and pancytopenia, and awareness may allow care related to immune and infectious complications 30576410 NAXE 18453 128240 Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy (PEBEL) AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27122014; 27616477 NBAS 15625 51594 Infantile liver failure syndrome 2; Short stature, optic nerve atrophy, and Pelger-Huet anomaly (SOPH syndrome) AR N/A N/A Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20577004; 26073778 NBEA 7648 26960 Neurodevelopmental disorder with or without early-onset generalized epilepsy AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28554332; 30269351 NBEAL2 31928 23218 Gray platelet syndrome AR Pediatric Hematologic Hematologic Individuals may manifest with anemia (sometimes requiring RBC transfusions) due to bleeding tendencies, and preventive measures and treatment (eg, when surgery is needed) may be beneficial; Recognition of the development of myelofibrosis may also be beneficial in order to allow prompt management 5129551; 6156948; 3414674; 8192152; 20709904; 21765411; 21765412; 21765413; 23100277 NBN 7652 4683 Breast cancer, susceptibility to; Nijmegen breakage syndrome AD/AR Pediatric (Nijmegen breakage syndrome); Adult (Breast cancer, susceptibility to) Allergy/Immunology/Infectious; Hematologic; Musculoskeletal; Neurologic; Oncologic Allergy/Immunology/Infectious; Hematologic; Oncologic Variants may result in increased risk of a number of malignancies, including acute lymphoblastic leukemia In Breast cancer, susceptibility to, awareness may allow surveillance, preventive measures, and early recognition and treatment of disease; Nijmegen breakage syndrome may be recognizable, but surveillance for cancer may be beneficial, and specific treatment modalities may be preferable (eg, cytostatics are first-line, radiomimetics and radiation therapy should be avoided, and reduced-dose chemotherapy should be used); Surveillance and prompt treatment of hematologic manifestations (eg, aplastic anemia, bone marrow failure) may be beneficial; Due to immunodeficiency, early and aggressive treatment of infections can be beneficial 3802554; 7545870; 8929954; 9590181; 9590180; 15474156; 15338273; 16634478; 16033915; 20143155; 21166880; 21799032; 21700777; 20143155; 21656575; 22006311; 22070649; 22114071; 22373003; 22491912; 22864661 NCAPD2 24305 9918 Microcephaly 21, primary, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27737959; 28097321 NCAPD3 28952 23310 Microcephaly 22, primary, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27737959 NCAPG2 21904 54892 Kahn-Kahn-Katsanis syndrome AR N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30609410 NCAPH 1112 23397 Microcephaly 23, primary, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27737959 NCF1 7660 653361 Granulomatous disease, chronic, autosomal recessive, 1 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Surveillance for infections and infectious complications is indicatred, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation 5755008; 6848934; 3011845; 3339133; 2770793; 2011585; 11060536; 10706888; 11133775; 16972229; 19329991; 22157170; 22876374; 22924696 NCF2 7661 4688 Granulomatous disease, chronic, autosomal recessive, 2 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Surveillance for infections and infectious complications is indicatred, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation 2770793; 7795241; 10498624; 11060536; 22157170; 22876374; 23264412 NCF4 7662 4689 Granulomatous disease, chronic, autosomal recessive, 3 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Surveillance for infections and infectious complications is indicatred, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation 19692703; 22157170; 22876374 NCKAP1L 4862 3071 Immunodeficiency 72 with autoinflammation AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious The condition can involve early-onset and severe infections, as well as other immunologic manifestations, and awareness may allow early and aggressive treatment of infections; Medical management of autoimmune disease (with immunomodulatory agents) has been described as beneficial in some individuals 32647003 NCSTN 17091 23385 Acne inversa, familial 1 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20929727; 22622421 NDE1 17619 54820 Lissencephaly 4; Microhydranencephaly AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10762554; 21529751; 21529752; 22526350 NDNF 26256 79625 Hypogonadotropic hypogonadism 25 with anosmia AD Pediatric Endocrine; Genitourinary; Neurologic Endocrine In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 20301509; 31883645 NDP 7678 4693 Norrie disease; Exudative vitreoretinopathy, 2, X-linked XL N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 95062; 1303235; 1307245; 1642288; 8252044; 8457509; 8110678; 7662640; 7814011; 7795608; 7627181; 8990009; 17325173; 17334993; 20301506; 20491809; 20679667; 21179243; 21960066; 22563645; 22674248 NDRG1 7679 10397 Charcot-Marie-Tooth disease, type 4D AR N/A N/A Audiologic/Otolaryngologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10831399; 22978647; 23163601; 24136616 NDST1 7680 3340 Mental retardation, autosomal recessive 46 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21937992; 25125150 NDUFA1 7683 4694 Mitochondrial complex I deficiency, nuclear type 12 XL N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 17262856; 21596602 NDUFA10 7684 4705 Mitochondrial complex I deficiency, nuclear type 22; Leigh syndrome AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 21150889 NDUFA11 20371 126328 Mitochondrial complex I deficiency, nuclear type 14 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 18306244 NDUFA12 23987 55967 Mitochondrial complex I deficiency, nuclear type 23; Leigh syndrome AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21617257 NDUFA13 17194 51079 Thyroid carcinoma, Hurthle cell AD Adult Allelic with Mitochondrial complex I deficiency, nuclear type 28 (AR) Biochemical; Neurologic; Oncologic; Ophthalmologic Oncologic In Mitochondrial complex I deficiency, medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Surveillance and/or awareness of thyroid cancer risk may allow early diagnosis and treatment of neoplasms, which may improve outcomes 15841082; 25901006 NDUFA2 7685 4695 Mitochondrial complex I deficiency, nuclear type 13; Leigh syndrome AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 18513682 NDUFA4 7687 4697 Mitochondrial complex IV deficiency, nuclear type 21 AR N/A N/A Biochemical; Musculoskeletal; Neurologic Biochemical In addition to other features, individuals have been described as presenting in infancy with lactic acidosis, necessitating treatment with sodium bicarbonate 23746447 NDUFA6 7690 4700 Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, uniquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30245030 NDUFA8 7692 4702 Mitochondrial complex I deficiency, nuclear type 37 AR N/A N/A Biochemical; Neurologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32385911; 33153867 NDUFA9 7693 4704 Mitochondrial complex I deficiency, nuclear type 26; Leigh syndrome AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22114105 NDUFAF1 18828 51103 Mitochondrial complex I deficiency, nuclear type 11 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 17557076; 21931170 NDUFAF2 28086 91942 Mitochondrial complex I deficiency, nuclear type 10; Leigh syndrome AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 16200211; 20571988; 20818383 NDUFAF3 29918 25915 Mitochondrial complex I deficiency, nuclear type 18 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 19463981 NDUFAF4 21034 29078 Mitochondrial complex I deficiency, nuclear type 15 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 18179882 NDUFAF5 15899 79133 Mitochondrial complex I deficiency, nuclear type 16 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 18940309; 19542079; 21607760 NDUFAF6 28625 137682 Fanconi renotubular syndrome 5 AR Pediatric Allelic with Mitochondrial complex I deficiency, nuclear type 17 (AR) Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary; Renal Renal In Mitochondrial complex I deficiency, nuclear type 17, medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Individuals with Fanconi renotubular syndrome may have renal tubular disease, and medical management (eg, correction of acidosis, phosphate, and vitamin D levels) has been shown to be beneficial; Renal transplant has been described 17690917; 18614015; 27466185 NDUFAF8 33551 284184 Mitochondrial complex I deficiency, nuclear type 34 AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31866046 NDUFB10 7696 4716 Mitochondrial complex I deficiency, nuclear type 35 AR N/A N/A Biochemical; Cardiovascular General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28040730 NDUFB11 20372 54539 Linear skin defects with multiple congenital anomalies 3 XL Pediatric Allelic with Mitochondrial complex I deficiency, nuclear type 30 (XL) Biochemical; Cardiovascular; Dermatologic; Neurologic Cardiovascular Cardiac transplantation has been described Among other findings, individuals have been described with early-onset cardiomyopathy, and awareness may allow prompt awareness and management 25772934; 26741492 NDUFB3 7698 4709 Mitochondrial complex I deficiency, nuclear type 25 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 15534765; 22277967 NDUFB8 7703 4714 Mitochondrial complex I deficiency, nuclear type 32 AR N/A N/A Biochemical; Cardiovascular; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29429571 NDUFB9 7704 4715 Mitochondrial complex I deficiency, nuclear type 24 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22200994 NDUFC2 7706 4718 Mitochondrial complex I deficiency, nuclear type 36 AR N/A N/A Biochemical; Cardiovascular; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32969598 NDUFS1 7707 4719 Mitochondrial complex I deficiency, nuclear type 5 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 11349233; 15824269; 16478720; 20382551; 21203893 NDUFS2 7708 4720 Mitochondrial complex I deficiency, nuclear type 6 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 11220739; 20819849; 22036843 NDUFS3 7710 4722 Mitochondrial complex I deficiency, nuclear type 8; Leigh syndrome AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 14729820; 22499348; 33097395 NDUFS4 7711 4724 Mitochondrial complex I deficiency, nuclear type 1; Leigh syndrome AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9463323; 10944442; 11743516; 11181577; 12616398; 16478720; 19107570; 19364667; 22326555 NDUFS6 7713 4726 Mitochondrial complex I deficiency, nuclear type 9 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 15372108; 19259137 NDUFS7 7714 374291 Mitochondrial complex I deficiency, nuclear type 3; Leigh syndrome AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10330338; 11743516; 17275378; 17604671 NDUFS8 7715 4728 Mitochondrial complex I deficiency, nuclear type 2; Leigh syndrome AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9837812; 11743516; 15159508 NDUFV1 7716 4723 Mitochondrial complex I deficiency, nuclear type 4 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10080174; 11743516; 18991197; 21696386 NDUFV2 7717 4729 Mitochondrial complex I deficiency, nuclear type 7 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 12754703; 21548921 NEB 7720 4703 Nemaline myopathy 2, autosomal recessive; Arthrogryposis multiplex congenita 6 AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10051637; 10619714; 12207937; 15221447; 16917880; 19232495; 19805734; 21798101; 22367672; 23010307; 25205138; 26578207; 27933661; 28336317; 29274205; 33376055 NECAP1 24539 25977 Developmental and epileptic encephalopathy 21 AR N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24399846; 30525121; 30626896 NECTIN1 9706 5818 Cleft lip/palate-ectodermal dysplasia syndrome AD/AR N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10932188; 11559849 NECTIN4 19688 81607 Ectodermal dysplasia-syndactyly syndrome 1 AR N/A N/A Dental; Dermatologic; Musculoskeletal General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1646587; 20691405; 21346770 NEDD4L 7728 23327 Periventricular nodular heterotopia 7 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27694961 NEFH 7737 4744 Charcot-Marie-Tooth disease, axonal, type 2CC AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27040688 NEFL 7739 4747 Charcot-Marie-Tooth disease, axonal, type 2E; Charcot-Marie-Tooth disease, dominant intermediate G; Charcot-Marie-Tooth disease, type 1F AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10841809; 12481988; 14733962; 15111691; 16619203; 17620486; 18758688; 19158810; 19286384; 20039262; 20301366; 22206013; 24887401; 25877835; 26645395; 28364294 NEK1 7744 4750 Short-rib thoracic dysplasia 6 with or without polydactyly AR/Digenic N/A Allelic with Amyotrophic lateral sclerosis, susceptibility to, 24 (AD) Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal General Heterozygous (digenic) variants in both NEK1 and DYNC2H1 can result in disease Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21211617; 22499340; 22795106; 22499340; 26945885; 27455347 NEK10 18592 152110 Ciliary dyskinesia, primary, 44 AR Pediatric Allergy/Immunology/Infectious; Pulmonary Allergy/Immunology/Infectious; Pulmonary Pulmonary surveillance may be beneficial to assess respiratory function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 20301301; 31959991 NEK2 7745 4751 Retinitis pigmentosa 67 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24043777 NEK8 13387 284086 Nephronophthisis 9; Renal-hepatic-pancreatic dysplasia 2 AR N/A N/A Cardiovascular; Gastrointestinal; Musculoskeletal; Pulmonary; Renal General While individuals were first described with having cystic kidneys, later reports included cysts affecting other organs, such as the liver and pancreas, as well as cardiac disease Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18199800; 23418306; 26697755; 26862157; 26967905 NEK9 18591 91754 Arthrogryposis, Perthes disease, and upward gaze palsy; Lethal congenital contracture syndrome 10 AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21271645; 26633546; 26908619 NEMF 10663 9147 Intellectual developmental disorder with speech delay and axonal peripheral neuropathy AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32934225; 33048237 NEPRO 24496 25871 Anauxetic dysplasia 3 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26633546; 29620724; 31250547 NEU1 7758 4758 Sialidosis, type I; Sialidosis, type II AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic ; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 610425; 610423; 107795; 6777097; 6839532; 3742847; 8985184; 9054950; 11063730; 11829139; 14695530; 15908988; 19568825 NEUROD1 7762 4760 Maturity onset diabetes of the young 6 AD N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10545951 NEUROD2 7763 4761 Developmental and epileptic encephalopathy 72 AD Pediatric Neurologic Neurologic The condition can include refractory seizures and other neurologic manifestations, and placement of a vagal-nerve stimulator has been reported as benefiting seizure control as well as development 30323019 NEUROG3 13806 50674 Diarrhea 4, malabsorptive, congenital AR Pediatric Endocrine; Gastrointestinal Gastrointestinal Individuals may present in infancy with severe hyperchloremic metabolic acidosis due to vomiting and diarrhea, and may require parenteral nutrition and limited enteral feeding (with oral vitamins and electrolyte supplementation); Surveillance may allow early recognition and treatment of diabetes mellitus (including with insulin); One reported individual required liver/intestinal transplant 16855267; 21490072 NEXMIF 29433 340533 Mental retardation, X-linked 98 XL N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15466006; 23615299 NEXN 29557 91624 Cardiomyopathy, familial hypertrophic, 20; Cardiomyopathy, dilated, 1CC AD Pediatric Cardiovascular Cardiovascular Surveillance (eg, including echocardiogram/electocardiogram) and preventive measures, including medical management, may reduce morbidity and severe sequelae such as sudden cardiac death; Cardiac transplantation has ben reported 19881492; 20970104 NF1 7765 4763 Neurofibromatosis type 1, Neurofibromatosis-Noonan syndrome; Watson syndrome AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic Cardiovascular; Oncologic; Ophthalmologic The condition can involve multiple organ systems affected by neoplastic and other complications that would warrant intervention As clinical diagnosis can be challenging early, and optic pathway gliomas affect approximately 15% of people with NF1 (a minority can cause blindness), children should undergo surveillance by a pediatric ophthalmologist to screen for evidence of optic nerve damage from an occult optic nerve glioma; Surveillance for other manifestations and their sequelae, such as cardiovacular anomalies, may also be beneficial; Awareness of the risk of malignancy (in addition to benign neurofibromas and optic gliomas, NF1 includes a risk of brain tumors, and malignant peripheral nerve sheath tumors, as well as hematologic malignancies) may allow prompt detection and management; An antineoplastic agent (selumetinib) has been reported to improve some clinical parameters, such as pain, quality of life, strength, and range of motion 6798841; 14050005; 6025371; 4965691; 4633999; 1131001; 6777096; 6786260; 6814376; 6417335; 6422759; 3083645; 3083258; 2897130; 2510517; 2134734; 1770531; 1909491; 1719426; 1302608; 8317503; 7931405; 7874161; 7477989; 7502979; 8644707; 9128932; 9126041; 9529361; 10204844; 10480204; 10699117; 10951462; 11078559; 11041400; 11292406; 11298367; 11704931; 11453810; 11176707; 11296017; 11283797; 12011145; 12180143; 12089128; 12707950; 12588224; 12566521; 15019338; 16380919; 15690406; 16787982; 17105749; 17362838; 17327286; 17932395; 19845691; 19449407; 19117870; 20301288; 22934576; 22943186; 22961690; 22965642; 22965773; 23047517; 23047742; 23060584; 23071069; 23099008; 23696535 23812910; 32187457 NF2 7773 4771 Neurofibromatosis type II; Schwannomatosis 2 AD Pediatric Oncologic Oncologic In order to detect neoplasms (individuals are predisposed to a variety of types of central nervous system tumors), surveillance with regular cranial MRI is indicated, which may allow detection and treatment; In the treatment of neoplasms, radiation therapy should be avoided (especially in childhood) due to the risk of causing or accelerating other neoplasms 5304294; 4990044; 1479599; 1479598; 8379998; 7913580; 7747758; 8188242; 8751853; 8755919; 9399891; 9643284; 9811917; 9817927; 9863591; 10569966; 10220142; 9874852; 10771486; 11159946; 11342693; 11425952; 12136076; 12235555; 12473765; 12011146; 12566519; 15190457; 15235024; 15831594; 15994874; 16341811; 16521120; 16534111; 16983642; 19476995; 19880713; 20301380; 21451418; 21358190; 22038540; 22098617; 22929112; 22931905; 22989157; 23682341; 23921933; 23931824; 23939548 NFASC 29866 23114 Neurodevelopmental disorder with central and peripheral motor dysfunction AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28940097; 30124836; 30850329 NFE2L2 7782 4780 Immunodeficiency, developmental delay, and hypohomocysteinemia (IMDDHH) AD Pediatric Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Gastrointestinal; Neurologic Allergy/Immunology/Infectious; Biochemical The condition can manifest with immunodeficiency (for which antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial), liver damage, and other features, and medical management (with luteolin and ascorbic acid) has been described as beneficial related to certain parameters, such as liver enzymes and reported frequency of infections 29018201 NFIA 7784 4774 Brain malformations with or without urinary tract defects AD Pediatric Neurologic; Renal Renal The condition can include renal anomalies such as hydronephrosis and vesicoureteral reflux and awareness may allow early management, which may help prevent or manage renal sequelae 17530927; 24462883; 27081522 NFIB 7785 4781 Macrocephaly, acquired, with impaired intellectual development AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30388402 NFIX 7788 4784 Marshall-Smith syndrome; Sotos syndrome 2 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20673863; 22301465; 22982744 NFKB1 7794 4790 Immunodeficiency, common variable, 12 AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described with immunodeficiency and recurrent infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 26279205 NFKB2 7795 4791 Immunodeficiency, common variable, 10 AD Pediatric Allergy/Immunology/Infectious; Endocrine; Renal Allergy/Immunology/Infectious; Endocrine Individuals have been described with immunodeficiency and recurrent infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Central adrenal insufficiency has been described, and medical management (with glucocorticoid and mineralocorticoid replacement) has been described as beneficial 24140114; 24888602; 25237204; 25524009; 31417880 NFKBIA 7797 4792 Ectodermal dysplasia and immunodeficiency 2 AD Pediatric Allergy/Immunology/Infectious; Dental; Dermatologic; Gastrointestinal Allergy/Immunology/Infectious Syndromic features may not be clinically recognizable prior to infectious manifestations In addition to ectodermal manifestations, individuals have immunodeficiency, and surveillance/prophylaxis/aggressive treatments of infection may be beneficial; BMT has been reported as effective 15337789; 16769798; 17931563; 18412279; 23708964; 23864385; 23870671; 26691317; 28417298; 28597146; 29948576 NFU1 16287 27247 Multiple mitochondrial dysfunctions syndrome 1 AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11156534; 21944046 NGF 7808 4803 Neuropathy, hereditary sensory and autonomic, type V AR N/A N/A Neurologic General Insensivity to pain may result in injuries and infections Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14976160; 20978020 NGLY1 17646 55768 Congenital disorder of deglycosylation AR Pediatric Biochemical; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 22581936; 24651605 NHEJ1 25737 79840 Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Some individuals may not demonstrate obvious dysmorphic features Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 12604777; 16439204; 16439205; 17191205; 20597108 NHLRC1 21576 378884 Epilepsy, progressive myoclonic 2B (Lafora) AR N/A N/A Neurologic General While antiepileptic drugs may be effective, certain medications (eg, phenytoin, and possibly carbamazepine, oxcarbazepine, and lamotrigine) can exacerbate myoclonus Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10513696; 14663053; 12958597; 15781812; 16021330; 16356781; 16950819; 19267391; 20301563 NHLRC2 24731 374354 Fibrosis, neurodegeneration, and cerebral angiomatosis AR N/A N/A Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Hematologic; Neurologic; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29423877 NHP2 14377 55651 Dyskeratosis congenita, autosomal recessive 2 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic; Oncologic; Pulmonary Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; Lung transplant may be indicated in individuals with advanced lung diease; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal 18523010; 20301779 NHS 7820 4810 Nance-Horan syndrome; Cataract 40 XL N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4470901; 458526; 11836358; 14564667; 15623749; 16736028; 17256798; 19414485; 20882036; 25266737 NIN 14906 51199 Seckel syndrome 7 AR N/A N/A Craniofacial; Endocrine; Musculoskeletal; Neurologic Endocrine The condition can include manifestations including endocrine anomalies (eg, hypothyroidism, hypogonadism), some of which may respond to appropriate hormonal therapy (eg, thyroid hormone replacemetn therapy, estrogen therapy) 22933543 NIPA1 17043 123606 Spastic paraplegia 6, autosomal dominant AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7854534; 14508710; 15711826; 21419568; 21599812; 22302102 NIPAL4 28018 348938 Ichthyosis, congenital, autosomal recessive AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15317751; 17557927; 20301593 NIPBL 28862 25836 Cornelia de Lange syndrome 1 AD N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Renal General Somatic mosaicism is relatively frequent Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2246693; 2333897; 8291513; 8281279; 8291537; 8291518; 9279756; 12784293; 15146185; 15146186; 15633188; 16236812; 16770807; 17661813; 20301283; 20358602; 20583156; 22241092; 22581668; 22676896; 22965847; 23254390; 23304577; 23313159; 23505322 NKAP 29873 79576 Intellectual developmental disorder, X-linked, syndromic, Hackman-Di Donato type XL Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General The condition can include cardiovascular anomalies, including valvular and other anomalies, and awareness may allow early detection (eg, via echocardiogram) and management 26358559; 31587868 NKX2-1 11825 7080 Choreoathetosis, hypothyroidism, and neonatal respiratory distress; Thyroid cancer, nonmedullary 1 AD Pediatric/Adult Allelic with Chorea, hereditary benign (AD) Allergy/Immunology/Infectious; Endocrine; Neurologic; Oncologic; Pulmonary Allergy/Immunology/Infectious; Endocrine; Neurologic; Oncologic; Pulmonary Choreoathetosis, hypothyroidism, and neonatal respiratory distress manifests in the childhood; Thyroid cancer, nonmedullary 4 has been reported as manifesting in adulthood Individuals with Choreoathetosis, hypothyroidism, and neonatal respiratory distress may have congenital hypothyroidism necessitating thyroxine replacement; Response to levodopa has also been reported; Neonates may require ventilatory support, and may be prone to recurrent respiratory infections, and awareness may allow prophylactic measures, as well as prompt and aggressive treatment of infections; For Thyroid cancer, nonmedullary 1, individuals have been described as being susceptible to nonmedullary thyroid cancer, and awareness may allow early surveillance, diagnosis, and management 9565498; 10931427; 11854319; 11854318; 11971878; 12891678; 15289765; 15955952; 19176457; 19336474; 22488412; 22825795 NKX2-5 2488 1482 Atrial septal defect 7, with or without AV conduction defects; Conotruncal heart malformations; Hypothyroidism, congenital nongoitrous, 5 AD Pediatric Allelic with Hypoplastic left heart syndrome 2 (AD); Ventricular septal defect 3 (AD); Conotruncal heart malformations, variable (AD); Tetralogy of Fallot (AD) Cardiovascular; Endocrine Cardiovascular; Endocrine Individuals may have arrhythmias as well as congenital cardiac malformations (and can have arrhthymias without obvious structural cardiac malformations), and surveillance and treatment may be beneficial; In Hypothyroidism, congenital nongoitrous, medical treatment for thyroid insufficiency may be effective, and individuals may also be at risk for cardiac anomalies 1260978; 9651244; 10587520; 11714651; 12414819; 14607454; 15810002; 16418214; 16896344; 20659440; 21110066; 19948535; 20456451; 21637914 NKX2-6 32940 137814 Persistent truncus arteriosus; Conotruncal heart malformations AR N/A N/A Cardiovascular General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15649947 NKX3-2 951 579 Spondylo-megaepiphyseal-metaphyseal dysplasia AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3925497; 13680008; 20004766 NKX6-2 19321 84504 Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28575651 NLGN1 14291 22871 Autism, susceptibility to, 20 AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28841651; 30460678 NLGN3 14289 54413 Asperger syndrome, X-linked 1; Autism, X-linked 1 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12669065 NLGN4X 14287 57502 Asperger syndrome, X-linked 2; Autism, X-linked 2; Mental retardation, X-linked XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12669065; 14963808; 18231125; 19645625; 19726642 NLRC4 16412 58484 Autoinflammation with infantile enterocolitis (AIFEC); Familial cold autoinflammatory syndrome 4 AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious In Autoinflammation with infantile enterocolitis, individuals present with recurrent autoinflammatory manifestations in infancy, and treatment with IL1R antagonists has been described as beneficial (decreased frequency of flares, corticosteroid requirements, and clinical and lab severity); In Familial cold autoinflammatory syndrome 4, manifestations frequently resolve without treatments, though analgesics may be helpful related to joint pain 25217959; 25217960; 25385754 NLRP1 14374 22861 Palmoplantar carcinoma, multiple self-healing; Autoinflammation with arthritis and dyskeratosis AD/AR Pediatric N/A Allergy/Immunology/Infectious; Dermatologic; Hematologic; Musculoskeletal; Oncologic; Ophthalmologic Hematologic; Oncologic Palmoplantar carcinoma involves recurrent palmoplantar, conjunctival, and corneal keratoacanthomas, and individuals have been described as having high susceptibility to malignant squamous cell carcinoma; Features of Autoinflammation with arthritis and dyskeratosis have been described as including anemia severe enough to necessitate splenectomy, and awareness may allow prompt diagnosis and management; Individuals were not reported to benefit from Vitamin A supplementation 23349227; 27662089; 27965258 NLRP12 22938 91662 Familial cold autoinflammatory syndrome 2 AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Medical treatment (eg, with prednisone or colchicine) has been reported as effective in reducing fever 18230725; 22753383; 27314497; 27633793 NLRP3 16400 114548 Chronic Infantile Neurologic Cutaneous Articular (CINCA) syndrome; Deafness, autosomal dominant, 34, with or without inflammation; Muckle-Wells syndrome; Neonatal Onset Multisystem Inflammatory Disease (NOMID) AD Pediatric Allelic with Familial cold-induced autoinflammatory syndrome 1 (AD) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Renal Allergy/Immunology/Infectious Individuals may present with autoinflammatory manifestions, which can be severe, progressive, and ultimately fatal, medical treatment with IL1R antagonists (eg, anakinra, canakinumab) has been described as an effective treatment 14476827; 5769632; 5173311; 49161; 447320; 11687797; 12032915; 12483741; 11992256; 12928894; 16532456; 21356079; 21538043; 21859692; 21967869; 22193915; 22723549; 28847925 NLRP7 22947 199713 Hydatidiform mole, recurrent, 1 AR Pediatric Obstetric; Oncologic Obstetric; Oncologic Women are likely to have pregnancies with hydatidiform moles, with a high risk of persistent trophoblastic disease, including requiring chemotherapeutic treatment, and awareness may allow reproductive planning and/or surveillance measures, which may allow early detection and treatment 16874523; 16462743; 19066229; 19246479; 22315435; 22770628; 23125094 NME8 16473 51314 Ciliary dyskinesia, primary, 6 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Pulmonary and audiologic surveillance may be beneficial to assess respiratoryand hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 17360648; 20301301 NMNAT1 17877 64802 Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis" AR Pediatric Allelic with Leber congenital amaurosis 9 (AR) Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic Audiologic/Otolaryngologic Among other findings, the condition can include sensorineural hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 22842227; 22842229; 22842230; 22842231; 32533184; 33668384 NNT 7863 23530 Glucocorticoid deficiency 4, with or without mineralocorticoid deficiency AR Pediatric Cardiovascular; Endocrine Cardiovascular; Endocrine The condition can involve early-onset life-threatening sequelae of glucocorticoid deficiency as well as later effects involving mineralocorticoid deficiency and other manifestations (eg, possible thyroid and cardiac findings) and awareness may allow preventive/treatment measures (eg, with corticosteroid replacement therapy) related to adrenal insufficiency 22634753; 23474776; 25879317; 26070314; 27129361 NOBOX 22448 135935 Premature ovarian failure 5 AD Pediatric Endocrine; Obstetric Obstetric Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency 17701902; 21837770; 25514101 NOD2 5331 64127 Blau syndrome; Sarcoidosis, early-onset AD/AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Musculoskeletal; Ophthalmologic; Pulmonary Allergy/Immunology/Infectious Variants may also be related to susceptibility to Yao syndrome Bi-allelic variants result in a ~40-fold higher relative risk of Crohn disease; In Blau syndrome, individuals have been described as responding to TNF-alpha or IL1B inhibitory medications 4056967; 3993660; 8394645; 8882056; 9508240; 11385576; 11528384; 12879366 ; 15086578; 15459013; 17698784; 17804789 ; 21788900; 21914217; 21951874; 22147245; 22509093; 22821420; 22859352; 23102769; 23124805; 26070941 NODAL 7865 4838 Heterotaxy, visceral, 5, autosomal AD N/A N/A Cardiovascular; Gastrointestinal; Pulmonary; Renal General The condition can involve multiple congenital anomalies; Cardiac transplantation has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19064609 NOG 7866 9241 Brachydactyly, type B2; Tarsal-carpal coalition syndrome; Multiple synostosis syndrome 1; Symphalangism, proximal, 1A; Stapes ankylosis with broad thumb and toes (Teunissen-Cremers syndrome) AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal Audiologic/Otolaryngologic Some conditions may be frequently recognizable based on clinical manifestations Hearing impairment may be prelingual in some individuals, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 7245852; 6638061; 4019538; 10080184; 10069712; 11545688; 1846737; 12089654; 15770128; 16532400; 17668388; 18440889; 20503332; 19471170; 20503332; 21358557; 21538686; 22855651 NOL3 7869 8996 Myoclonus, familial,1 AD N/A N/A Neurologic General The condition may be exacerbated by alcohol, and alleviated by medical treatment (eg, with clonazepam) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22926851 NONO 7871 4841 Mental retardation, X-linked, syndrome 34 XL N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26571461 NOP10 14378 55505 Dyskeratosis congenita, autosomal recessive 1 AR Pediatric Allergy/Immunology/Infectious; Dental; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic; Oncologic; Pulmonary Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; Lung transplant may be indicated in individuals with advanced lung diease; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal 17507419; 20301779 NOP56 15911 10528 Spinocerebellar ataxia 36 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21683323; 22744658; 22492559 NOS1AP 16859 9722 Nephrotic syndrome, type 22 AR N/A N/A Renal General Renal transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33523862 NOTCH1 7881 4851 Aortic valve disease 1 AD Pediatric Allelic with Adams-Oliver syndrome 5 (AD) Cardiovascular; Dermatologic; Musculoskeletal Cardiovascular Variants in some affected individuals were also found in apparently unaffected parents Individuals may have a variety of cardiovascular malformations, and early diagnosis and treatment (including surgical treatment in some individuals) may reduce morbidity and mortality 16025100; 18593716; 21785343; 22307742; 23102684; 23578328; 25132448; 25963545 NOTCH2 7882 4853 Alagille syndrome 2 AD Pediatric Allelic with Hajdu-Cheney syndrome (AD); Serpentine fibula-polycystic kidney syndrome (AD) Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal Cardiovascular; Gastrointestinal; Renal The condition may not be clinically apparent; for hepatic complications, medications (eg, ursodeoxycholic acid, cholestyramine), and, when necessary, partial external biliary diversion may be beneficial; other treatments, such as fat-soluble vitamin supplementation may be beneficial; Surveillance for other manifestations, including cardiac and renal manifestations (such as renal tubular acidosis, which has been described in affected individuals), may be beneficial in order to allow early diagnosis and treatment and/or preventive measures 18918373; 14303950; 8723560; 11343321; 16773578; 17159511; 20301450; 21378989; 21681853; 21378985; 21712856; 21793104; 21934706; 22209762; 22488849; 23117206; 23389697; 23401378; 23566664; 24265536 NOTCH2NLC 53924 100996717 Neuronal intranuclear inclusion disease; Tremor, hereditary essential, 6 AD N/A N/A Neurologic General Reported variants have involved repeat expansions in the 5-prime untranslated region of the NOTCH2NLC gene Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31332380; 31332381; 31819945; 32516806 NOTCH3 7883 4854 Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 (CADASIL1); Myofibromatosis, infantile 2 AD Pediatric Allelic with Lateral meningocele syndrome (AD) Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Oncologic Cardiovascular; Oncologic In Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 (CADASIL1), certain agents (eg, angiography, anticoagulants, thrombolytic therapy) should be avoided; Myofibromatosis, infantile 2 involves benign tumors affecting the skin, muscle, bone, and viscera, and awareness of visceral neoplasms may be beneficial in order to diagnose and manage lesions 7486874; 7564728; 7654071; 7500094; 8878478; 9188658; 9818928; 10371078; 12136071; 15096408; 15210914; 15313839; 15378071; 15666314; 16009764; 16263847; 15851739; 17135568; 16717210; 16864835; 18765654; 19174371; 20038773; 20301673; 21337686; 21671395; 22218279; 22996955; 23025651; 23696373; 23731542; 24000151; 25394726 NOVA2 7887 4858 Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32197073 NPAT 7896 4863 Nodular lymphocyte predominant Hodgkin lymphoma, familial AD Adult Oncologic Oncologic Individuals have been described as being at risk of nodular lymphocyte predominant Hodgkin lymphoma, and awareness may allow early disease detection and managament 21562039; 21778346 NPC1 7897 4864 Niemann-Pick disease, type C1; Niemann-Pick disease, type D AR N/A N/A Biochemical; Gastrointestinal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3865225; 3378364; 9211849; 9245994; 9634529; 9512307; 10361985; 10480349; 11182931; 12555942; 12408188; 15596783; 12955717; 15465421; 15465428; 16098014; 17497724; 17689147; 20301473; 19206179; 20484681; 32033912 NPC1L1 7898 29881 Ezetimibe, nonresponse to AD/AR Pediatric General Pharmacogenomic Variants may have pharmacogenomic relevance and medication selection may be affected in patients with variants 15679830; 20686565 NPC2 14537 10577 Niemann-pick disease, type C2 AR N/A N/A Biochemical; Gastrointestinal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; BMT has been described 8554047; 11125141; 11567215; 12447927; 17470133; 20301473; 20393800 NPHP1 7905 4867 Joubert syndrome 4; Nephronophthisis 1; Senior-Loken syndrome 1 AR N/A N/A Hematologic; Neurologic; Ophthalmologic; Renal General The conditions may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Renal transplant has been described, though nephrotic syndrome may recur post-transplantation Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14823504; 13763238; 13910672; 9326933; 9361039; 9856524; 10196704; 15138899; 16155189; 16571882; 20301500; 20454808; 20652329; 21068128; 21258817; 21866095; 23559409 NPHP3 7907 27031 Nephronophthisis 3; Meckel syndrome 7; Renal-hepatic-pancreatic dysplasia 1 AR N/A N/A Gastrointestinal; Hematologic; Musculoskeletal; Renal General Liver-kidney transplantation has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8874114; 12872122; 18371931; 19303681; 19177160; 20007846; 21068128; 21642631;21866095 NPHP4 19104 261734 Nephronophthisis 4; Senior-Loken syndrome 4 AR N/A N/A Ophthalmologic; Renal General Avoidance of certain medications (eg, nephrotoxic agents) may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12205563; 11920287; 12244321; 21068128; 21866095 NPHS1 7908 4868 Nephrotic syndrome, type 1 AR N/A N/A Renal General Medical therapy to control bacterial infections, along with renal transplantation, can be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6384451; 9660941; 10577936; 17413422; 17290294; 20650908; 20798252; 21125408; 22009864; 22565185; 22584503; 22653594 NPHS2 13394 7827 Nephrotic syndrome, type 2 AR N/A N/A Renal General The disease is steroid resistant; Partially steroid-responsive AD forms have been described; Renal transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8589695; 8606597; 10742096; 11729243; 12464671; 12707396; 17109732; 22036940; 22080622; 22228437; 22565185; 23013956 NPPA 7939 4878 Atrial fibrillation, familial, 6; Atrial standstill 2 AD/AR Adult Cardiovascular Cardiovascular The clinical onset of manifestations has been described in the adult period, but earlier surveillance may be beneficial Surveillance, preventive measures, and early medical intervention to prevent morbidity related to arrhthymias (atrial standstill/atrial fibrillation, depending on the inheritance pattern) may be beneficial 6225642; 18614783; 20064500; 20543198; 23275345 NPR2 7944 4882 Epiphyseal chondrodysplasia, Miura type; Short stature with nonspecific skeletal abnormalities; Acromesomelic dysplasia, Maroteaux type AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15146390; 16384845; 22691581; 22870295; 24001744; 24057292; 24259409; 24471569; 26336901; 26537434 NPRL2 24969 10641 Epilepsy, familial focal, with variable foci 2 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26505888; 27173016 NPRL3 14124 8131 Epilepsy, familial focal, with variable foci 3 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26285051; 26505888; 27173016 NR0B1 7960 190 Adrenal hypoplasia, congenital; 46,XY sex reversal 2 XL Pediatric Endocrine; Genitourinary; Obstetric; Oncologic Endocrine; Genitourinary; Obstetric; Oncologic Digenic inheritance (with GNRH1) has been reported; Dosage-sensitive sex reversal has been described due to duplications Affected individuals typically present in infancy with acute-onset adrenal insufficiency, which can be lethal, and preventive and treatment measures can be effective; In individuals with hypogonadotropic hypogonadism, testosterone may be required to induce puberty; Surgical interventions may decrease the risk of gonadal tumors 6891556; 7951319; 7990958; 9003500; 9529340; 10022408; 11549627; 11788621; 12519885; 17503084; 17164309; 20301604; 20301714; 21408189; 21632081; 21739173; 21925982; 22456342; 22570964 NR1H4 7967 9971 Cholestasis, progressive familial intrahepatic 5 AR Pediatric Gastrointestinal Gastrointestinal The condition involves rapidly progressive, neonatal-onset intralobular cholestasis leading to liver failure and death without liver transplant 26888176 NR2E3 7974 10002 Enhanced S-cone syndrome; Retinitis pigmentosa 37 AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13553271; 11071390; 10655056; 15229190; 17564971; 18294254; 20212206; 21364904; 22605927; 22807301 NR2F1 7975 7025 Bosch-Boonstra optic atrophy syndrome AD N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24462372 NR2F2 7976 7026 Congenital heart defects, multiple types; 46 XX sex reversal 5 AD N/A N/A Cardiovascular; Craniofacial; Endocrine; Genitourinary; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18371933; 24702954; 29478779; 31687637 NR3C1 7978 2908 Glucocorticoid resistance AD/AR Pediatric Endocrine Endocrine Treatment focuses on suppression of excess ACTH production, and may include high-dose mineralocorticoid-sparing synthetic glucocorticoids; Individuals may also display other endocrinologic anomalies (eg, growth hormone deficiency), and surveillance and prompt recognition and treatment may be beneficial 186477; 6841559; 2996089; 1704018; 8445027; 8863343; 11701741; 11589680; 11932321; 12050230; 12754700; 14764810; 15769988; 16449337; 17635946; 18319312; 19694013; 19933394; 23076843 NR3C2 7979 4306 Pseudohypoaldosteronism type I, autosomal dominant; Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy AD Pediatric Obstetric; Renal Obstetric; Pharmacogenomic; Renal In Pseudohypoaldosteronism type I, autosomal dominant Although the disorder may eventually become asymptomatic, individuals can present with neonatal salt wasting, and prompt recognition and treatment of electrolyte imbalances (eg, with sodium supplementation) can be beneficial; In Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy, hypertension can be severe, and present relatively early in life, and additionally may be exacerbated in pregnancy, and may be accompanied by findings such as hypokalemia, and may necessitate interventions including delivery; It has been suggested the spironolactone is contraindicated 1939532; 9662404; 10884226; 11134129; 11344206; 12788847; 16954160; 16972228; 20453518; 21159846; 21903996; 21932599 NR5A1 7983 2516 Adrenocortical insufficiency; 46,XX sex reversal 4; 46, XY sex reversal 3; Premature ovarian failure 7 AD/AR Pediatric Allelic with Spermatogenic failure 8 (AD) Endocrine; Genitourinary; Obstetric; Oncologic Endocrine; Genitourinary; Obstetric; Oncologic In adrenocortical insufficiency, which can manifest with severe electrolyte abnormalities and neurologic sequelae, recognition may allow beneficial medical management (eg, with hydrocortisone, fludrocortisone); In 46, XX and 46, XY sex reversal surgical removal of abdominal dysgenetic gonads and streak gonads is indicated due to increased risk of tumors; In 46, XY sex reversal, it has been suggested that early sperm cryopreservation may be beneficial for males to allow reproduction; Hormone replacement therapy may be beneficial in puberty; In Premature ovarian failure 7, genetic knowledge may be beneficial to allow Interventions such as preserving eggs in women with premature ovarian insufficiency 1956279; 10369247; 11038323; 11932325; 15070943; 15579739; 15472171; 16439367; 16684822; 17200175; 17694559; 19246354; 19318730; 19439508; 19849982; 20301714; 20453312; 20861607; 20887963; 21163476; 21535007; 21654157; 21691975; 22028768; 22080441; 22474171; 22549935; 22907560; 22909003; 23044873; 23095176; 23096908; 23153500; 23168057; 23299922; 23543655; 23918653; 24067197; 24073220; 24157186; 24231572; 27378692; 27610946; 27490115; 27855412 NRAS 7989 4893 Autoimmune lymphoproliferative syndrome type IV; Noonan syndrome 6 AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic; Oncologic Cardiovascular; Oncologic Noonan syndrome may include multiple congenital anomalies The condition may also include cardiac anomalies and dysrhythmias, and appropriate care may be beneficial; Individuals with Autoimmune lymphoproliferative syndrome type IV may be at risk of hematologic malignancies, and individuals with Noonan syndrome 6 have been described with juvenile myelomonocytic leukemia such that surveillance/early treatment may reduce morbidity 17517660; 19775298; 19966803; 20301303; 21901340; 22855653; 22887781 NRIP1 8001 8204 Congenital anomalies of the kidney and urinary tract 3 AD Pediatric Allelic with Schizophrenia (AD) Neurologic; Renal Renal Evidence or clinical applicability is unclear 21743468; 28381549 NRL 8002 4901 Retinitis pigmentosa 27; Clumped pigmentary retinal degeneration AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10192380; 11039579; 12796249; 15591106; 17335001 NRROS 24613 375387 Seizures, early-onset, with neurodegeneration and brain calcification AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32100099; 32197075 NRXN1 8008 9378 Schizophrenia 17; Pitt-Hopkins-like syndrome 2 AD/AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18369103; 17989066; 18945720; 19896112; 21424692 NSD1 14234 64324 Sotos syndrome 1; Weaver syndrome; Beckwith-Wiedemann syndrome AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Cardiovascular; Oncologic; Renal The conditions may include multiple congenital anomalies While only reported in the minority of individuals, individuals are at increased risk of malignancy, and recognition may allow prompt diagnosis and treatment; Surveillance for cardiac and renal complications may also be beneficial in order to allow prompt recognition and management 14148233; 4366187; 6324572; 3565472; 2319581; 1552397; 10507738; 10434127; 11146472; 11078573; 11813184; 11896389; 12464997; 12525543; 14517949; 14571271; 14997421; 15125616; 16010674; 15452385; 15362962; 15455365; 15365454; 16170239; 15942875; 15852475; 16222665; 16780628; 16329110; 17825104; 17480008; 17420391; 18304174; 19914434; 20101679; 20420030; 21677402; 21738022; 21834047; 22012791; 21342349; 20301652 NSDHL 13398 50814 Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome); CK syndrome XL N/A N/A Cardiovascular; Dermatologic; Musculoskeletal; Pulmonary; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5696317; 7408908; 8882402; 10710233; 10710235; 11907515; 12966526; 19842190; 19377476; 20605772; 21129721; 21290788 NSMCE2 26513 286053 Seckel syndrome 10 AR Pediatric Cardiovascular; Craniofacial; Endocrine; Musculoskeletal Cardiovascular; Musculoskeletal Among other features, individuals have been described with childhood-onset hypertriglyceridemia, and awareness may allow early diagnosis and dietary/medical management; An individual has been described with aortic aneurysm, and awareness may allow surveillance and early diagnosis and management 25105364 NSMCE3 7677 56160 Lung disease, immunodeficiency, and chromosome breakage syndrome AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Pulmonary Allergy/Immunology/Infectious Individuals have been described with severe and early-onset infections, and early awareness may allow preventive measures and early and aggressive treatment of infections 27427983 NSMF 29843 26012 Hypogonadotropic hypogonadism 9 with or without anosmia AD Pediatric Endocrine; Neurologic General Hormonal treatment may be effective to induce and maintain secondary sex characteristics, as well as to allow reproduction; Syngergistic effects (eg, with FGFR1) have been reported Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15362570; 17235395; 21300340; 21700882; 22035731 NSUN3 26208 63899 Combined oxidative phosphorylation deficiency 48 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27356879; 32488845 NT5C2 8022 22978 Spastic paraplegia 45 AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19415352; 24482476 NT5C3A 17820 51251 Uridine 5-prime monophosphate hydrolase deficiency, hemolytic anemia due to AR Pediatric Hematologic Hematologic The condition may manifest with hereditary hemolytic anemia, and transfusions have been reported as necessary (though only infrequently in the described individuals) 4372252; 6317231; 6307548; 3352512; 11369620; 16402212; 17128459; 18499901 NT5E 8021 4907 Calcification of joints and arteries AR N/A N/A Cardiovascular; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21288095 NTF4 8024 4909 Glaucoma 1, open angle, O AD Adult Ophthalmologic Ophthalmologic; Pharmacogenomic Open-angle glaucoma is typically asymptomatic until late stages, when irreversible nerve damage has already taken place; Agents that may contribute to glaucoma should be avoided 19765683; 20215012 NTHL1 8028 4913 Familial adenomatous polyposis 3 AR Adult Oncologic Oncologic Individuals have been described as affected by multiple types of cancer, including colorectal cancer, endometrial cancer, and other neoplasms, and awareness may allow surveillance and early management 25938944; 26559593 NTN1 8029 9423 Mirror movements 4 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28945198 NTNG2 14288 84628 Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31372774; 31692205; 31668703 NTRK1 8031 4914 Insensitivity to pain, congenital, with anhidrosis AR Pediatric Allelic with Medullary thyroid carcinoma, familial (AD), but the evidence/clinical applicability is unclear Allergy/Immunology/Infectious; Dermatologic; Neurologic Allergy/Immunology/Infectious; Dermatologic; Neurologic Individuals may manifest with poor thermoregulation due to anhidrosis, which may result in potentially severe fevers, and awareness can allow measures to help control temperature in order to decrease potential sequelae; Congenital insensitivity to pain can result in injuries, some of which may in theory be preventable with early diagnosis and preventive measures (eg, tooth extraction may be indicated); Recurrent infections have been described, and preventive measures and awareness allowing early diagnosis and aggressive treatmentment of infections may be beneficial 8696348; 10088743; 10861667; 11744315; 12949319; 15534759; 15695606; 16490492; 19618435; 20301726; 19089473; 17915006; 20647579; 21559108; 21708027; 22032467; 22355435; 22653642; 22814739; 22957891; 23112235 NTRK2 8032 4915 Obesity, hyperphagia, and developmental delay AD N/A Allelic with Developmental and epileptic encephalopathy 58 (AD) Endocrine; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15494731; 27884935; 29100083 NUBPL 20278 80224 Mitochondrial complex I deficiency, nuclear type 21 AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may have cardiac involvement Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11743516; 20818383; 23553477; 31917109 NUDT15 23063 55270 Thiopurines, poor metabolism of, 2 AD Pediatric General Pharmacogenomic Individuals have been reported as having severe hematopoietic toxicity when treated with standard doses of thiopurines, and awareness may allow adjustments to the medication regimen 25108385; 26878724 NUP107 29914 57122 Nephrotic syndrome, type 11; Ovarian dysgenesis 6; Galloway-Mowat syndrome 7 AR N/A N/A Craniofacial; Endocrine; Musculoskeletal; Neurologic; Obstetric; Renal General In Nephrotic syndrome and Galloway-Mowat syndrome, renal transplantation has been described; In Ovarian dysgenesis, to induce/maintain secondary sex characteristics, specific interventions (eg, medical hormonal treatment) may be necessary Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25558065; 26411495; 26485283; 28117080; 28280135; 30179222 NUP133 18016 55746 Nephrotic syndrome, type 18; Galloway-Mowat syndrome 8 AR N/A N/A Audiologic/Otolaryngologic; Craniofacial; Neurologic; Renal General In Galloway-Mowat syndrome, renal transplantation has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11793129; 30179222; 30427554 NUP155 8063 9631 Atrial fibrillation 15 AR Pediatric Cardiovascular Cardiovascular Though described individuals have suffered early morbidity and mortality despite early recognition and management, it is possible that preventive measures (including medical and surgical treatments) may be beneficial related cardiac arrthymias (atrial fibrillation) 15596564; 19070573 NUP160 18017 23279 Nephrotic syndrome, type 19 AR N/A N/A Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30179222 NUP188 17859 23511 Sandestig-Stefanova syndrome AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32021605; 32275884 NUP205 18658 23165 Nephrotic syndrome, type 13 AR N/A N/A Renal General Renal transplantation has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26878725 NUP214 8064 8021 Encephalopathy, acute, infection-induced, suseptibility to, 9 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30758658; 31178128 NUP37 29929 79023 Microcephaly 24, primary, autosomal recessive AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30179222 NUP62 8066 23636 Striatonigral degeneration, infantile AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3729745; 12374138; 14718703; 16786527 NUP85 8734 79902 Nephrotic syndrome, type 17 AR N/A N/A Musculoskeletal; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30179222 NUP88 8067 4927 Fetal akinesia deformation sequence 4 AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30543681 NUS1 21042 116150 Mental retardation, autosomal dominant, 55, with seizures; Congenital disorder of glycosylation, type 1aa AD/AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25066056; 29100083 NUTM2B-AS1 51204 101060691 Oculopharyngeal myopathy with leukoencephalopathy 1 AD N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31332380 NXF5 8075 55998 Familial heart block and focal segmental glomerulosclerosis XL Pediatric Allelic with Mental retardation, syndromic, X-linked (XL) Cardiovascular; Neurologic; Renal Cardiovascular For Mental retardation, syndromic, X-linked, the evidence of variants as being related to disease causation has been questioned due to subsequent population-based studies In Familial heart block and focal segmental glomerulosclerosis, awareness of the risk of cardiac complications, including progressive heart block, may allow surveillance (eg, with electrocardiogram) and treatment (eg, with pacemaker placement); Renal transplant has been described 11566096; 23686279; 23871722 NXN 18008 64359 Robinow syndrome, autosomal recessive 2 AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29276006 NYX 8082 60506 Night blindness, congenital stationary, type 1A XL N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8434607; 9662400; 11062471; 11062472; 16670814; 18617546; 20301423; 20850105; 22183355 OAT 8091 4942 Gyrate atrophy of choroid and retina AR Pediatric Biochemical; Musculoskeletal; Neurologic; Ophthalmologic Biochemical Dietary management (eg, with arginine restriction) may be beneficial 4122112; 572946; 7444439; 7356686; 3339136; 1737786; 11831916; 10604138; 110617919; 1297489; 15750329; 22674428 OBSL1 29092 23363 Three M syndrome 2 AR N/A N/A Craniofacial; Endocrine; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19481195; 23457316; 27796265 OCA2 8101 4948 Albinism, oculocutaneous, type II; Albinism, brown oculocutaneous; Skin/hair/eye pigmentation 1 AD/AR N/A N/A Dermatologic; Ophthalmologic General In Albinism, oculocutaneous, type II; Albinism, brown oculocutaneous, Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Skin/hair/eye pigmentation 1 is a susceptibility factor locus for a multifactorial disease (melanoma) 14904868; 687204; 7920637; 8302318; 7874125; 7762554; 7887411; 8723691; 10649493; 11179026; 12163334; 14704187; 15889046; 16341609; 17236130; 17952075; 18449927; 18680187; 20861488; 21471978; 21085994; 23103111 OCLN 8104 100506658 Pseudo-TORCH syndrome 1 (Band-like calcification with simplified gyration and polymicrogyria) AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19012351; 19530192; 20727516 OCRL 8108 4952 Dent disease 2; Lowe syndrome XL Pediatric Musculoskeletal; Neurologic; Ophthalmologic; Renal Pharmacogenomic; Renal In Dent disease, surveillance and treatment related to manifestations such as hypercalciuria in order to prevent kidney stones, nephrocalcinosis, and to delay the progression of kidney dysfunction may be beneficial (though efficacy is unclear, treatment may include thiazide diuretics, ACE inhibitors, and ARBs); Vitamin D and phosphorous may be beneficial related to skeletal manifestations; Growth hormone may be indicated; Nephrotoxic agents (eg, NSAIDs, aminoglycosides) should be avoided; In Lowe syndrome, which may represent the severe end of of the spectrum of variant-positive individuals, similar treatment related to renal manifestations may be beneficial, as well as care related to other organ systems 8504307; 9199559; 9632163; 9682219; 199559; 9917791; 10364518; 0923037; 10767176; 15627218; 17162149; 19390221; 21031565 ODAD1 26560 93233 Ciliary dyskinesia, primary, 20 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 23261302; 23261303 ODAD2 25583 55130 Ciliary dyskinesia, primary, 23 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations 23849778; 24203976 ODAD3 28303 115948 Ciliary dyskinesia, primary, 30 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Musculoskeletal; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 25192045; 25224326 ODAD4 25280 83538 Ciliary dyskinesia, primary, 35 AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal Allergy/Immunology/Infectious; Pulmonary The condition can involve multiple anomalies Pulmonary surveillance may be beneficial to assess respiratory function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 27486780 ODAPH 26300 152816 Amelogenesis imperfecta, hypomaturation type, IIA4 AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22901946 ODC1 8109 4953 Neurodevelopmental disorder with alopecia and brain imaging abnormalities (Bachmann-Bupp syndrome) AD N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30239107; 30475435 OFD1 2567 8481 Orofaciodigital syndrome 1; Simpson-Golabi-Behmel syndrome type 2; Joubert syndrome 10; Retinitis pigmentosa 23 XL N/A N/A Craniofacial; Dental; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Pulmonary; Renal General The conditions can involve multiple congenital anomalies, as well as, in some individuals, recurrent respiratory infections Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15444577; 13707262; 1248177; 11179005; 16783569; 16397067; 19800048; 20301500; 20301367; 20818665; 21729220; 22353940; 22548404; 22619378; 23033313 OGT 8127 8473 Mental retardation, X-linked 106 XL N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28302723; 28584052 OPA1 8140 4976 Glaucoma, normal tension, susceptibility to AD Adult Allelic with Optic atrophy 1 (AD); Optic atrophy with or without deafness (AD); Ophthalmoplegia, myopathy, ataxia, and neuropathy (AD) (in which deafness has been reported as occuring in early childhood, but is typically later-onset); Behr synrome (AR); Mitochondrial DNA depletion syndrome 14 (AR) Audiologic/Otolaryngologic; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic Ophthalmologic; Pharmacogenomic As IOP is normal and patients usually have good central vision, normal tension glaucoma is underdiagnosed tends to presents late, and genetic knowledge could allow preventive measures and treatment related to vision preservation; Agents that may contribute to glaucoma should be avoided 6493699; 4058877; 11017080; 11017079; 12566046; 15505825; 15531309; 16240368; 15781809; 16158427; 17306754; 18158317; 18496845; 18195150; 18065439; 19029523; 18287570; 19181907; 20417568; 20417570; 20157015; 21621262; 21636302; 20837821; 22776096; 22857269; 22042570; 22382025; 25012220; 25012222; 25146916; 26561570 OPA3 8142 80207 3-methylglutaconic aciduria, type III; Optic atrophy 3, autosomal dominant AD/AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2494568; 7510656; 11668429; 12126933; 15342707; 22776096; 23700088; 24749080; 26190011 OPHN1 8148 4983 Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance XL N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9582072; 12807966; 16158428; 16221952; 20528889 OPLAH 8149 26873 5-oxoprolinase deficiency AR N/A N/A Biochemical; Gastrointestinal; Renal General Transient neonatal hypoglycemia has been reported Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6113726; 6790862; 8127060; 21651516 OPN1LW 9936 5956 Colorblindness, partial, protan series; Blue cone monochromacy; Red cone polymorphism XL (involving both OPN1 genes) N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2847528; 2788922; 1881435; 1415215; 1302020; 8213841; 8792812; 10982039; 11772996; 12051694; 20579627; 23139274 OPN1MW 4206 2652 Colorblindness, partial, deutan series; Cone dystrophy 5, X-linked; Blue cone monochromacy XL (involving both OPN1 genes) N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2788922; 1881435; 1302020; 8213841; 8666378; 10982039; 11772996; 15094734; 19421413; 20579627; 23139274 OPN1SW 1012 611 Tritanopia AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14946611; 1531728 OPTN 17142 10133 Glaucoma, normal tension, susceptibility to; Glaucoma primary open angle AD Adult Allelic with Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia (AD/AR) Neurologic; Ophthalmologic Ophthalmologic; Pharmacogenomic Open-angle glaucoma is typically asymptomatic until late stages, when irreversible nerve damage has already taken place; Agents that may contribute to glaucoma should be avoided 11834836; 17389490; 20428114; 21613650; 21644038; 21730848; 22708870; 22402017; 23062601; 21852022; 21802176 ORAI1 25896 84876 Immunodeficiency 9 AR Pediatric Allelic with Myopathy, tubular aggregate, 2 (AD) Allergy/Immunology/Infectious; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Antiinfectious prophylaxis; early and aggressive treatment of infections 8814256; 15452313; 16582901; 21873530; 24591628; 25227914 ORC1 8487 4998 Meier-Gorlin syndrome 1 AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 819054; 11477602; 14564153; 21358632; 21358633; 21358631; 22333897 ORC4 8490 5000 Meier-Gorlin syndrome 2 AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11477602; 21358632; 21358631; 22333897 ORC6 17151 23594 Meier-Gorlin syndrome 3 AR N/A N/A Craniofacial; Genitourinary; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7710253; 21358632; 22333897 OSBPL2 15761 9885 Deafness, autosomal dominant 67 AD N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25077649; 25759012 OSGEP 18028 55644 Galloway-Mowat syndrome 3 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28272532; 28805828 OSMR 8507 9180 Amyloidosis, primary localized cutaneous, 1 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18179886; 19690585 OSTM1 21652 28962 Osteopetrosis, autosomal recessive 5 AR N/A N/A Hematologic; Musculoskeletal; Neurologic; Ophthalmologic General HSCT has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3513575; 10325711; 12627228; 15177004; 15108279; 16813530; 17922613; 17985267; 19507210 OTC 8512 5009 Ornithine transcarbamylase deficiency XL Pediatric Biochemical; Gastrointestinal; Neurologic Biochemical; Pharmacogenomic While males are typically severely affected and may require liver transplant (therapy with modalities such as adult derived human liver stem/progenitor cells has also been described), the presentation in females may be more subtle Treatment to prevent and treat severe sequelae can be beneficial, including prompt recognition and management of acute decompensation (eg, with rapid measures to control hyperammonemia, such as with dialysis, nitrogen scavengers therapy, appropriate treatment related to catabolism and hydration, and replacement of citrulline/arginine); Long-term dietary measures (eg, decreasing the nitrogen load with low protein diet, use of nitrogen scavengers, and administration of arginine/citrulline) may be beneficial; Certain agents (eg, valproate, haloperidol, and systemic corticosteroids, as well as triggers such as fasting, and physical/psychological stress, with specific considerations during pregnancy to decrease the risk of catabolism) should be avoided due to the potential of adverse events; Hepatic transplant is considered in certain individuals with frequent hyperammonemic episodes, and has been described in infancy 13975632; 6112522; 7351973; 7078580; 7151305; 6427608; 3001312; 2983225; 3945292; 3826955; 3202644; 2843770; 3170748; 1671317; 2342525; 2298453; 1720458; 1549234; 8364586; 8778603; 8786061; 10946359; 11804205; 12063505; 18071043; 20142522; 20301396; 20458665; 20497355; 20817516; 21061009; 21585627; 21642786; 21884343; 21918856; 21926883; 21956151; 22138526; 22232626; 22264779; 22340867; 22507172; 22563224; 22583334; 22594780; 22727265; 22728053; 23209112; 23231960; 23278509; 23283608; 23430866; 23551631; 23568734; 23640148; 23790482; 24006547; 24073003; 24113687; 24142276; 25135652; 29396029; 31441224 OTOA 16378 146183 Deafness, autosomal recessive 22 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 11972037; 19888295 OTOF 8515 9381 Deafness, autosomal recessive 9; Neuropathy, autosomal recessive, 1 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Individuals with NSRAN can have normal otoacoustic emissions test, but pure-tone audiometry/ABR will show abnormalities Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 10192385; 12114484; 12525542; 16097006; 16371502; 19461658 OTOG 8516 340990 Deafness, autosomal recessive 18B AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 23122587 OTOGL 26901 283310 Deafness, autosomal recessive 84B AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 23122586 OTUD5 25402 55593 Multiple congenital anomalies-neurodevelopmental syndrome, X-linked XL N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33131077; 33523931 OTUD6B 24281 51633 Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies (IDDFSDA) AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28343629 OTULIN 25118 90268 Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious The condition can manifest in early childhood with a variety of autoinflammatory sequelae, and patients has been described as responding to medical management (eg, with systemic steroids, IL1R antagonist, TNF inhibitor) 27523608; 27559085 OTX2 8522 5015 Pituitary hormone deficiency, combined 6; Microphthalmia, syndromic 5; Retinal dystrophy, early-onset, and pituitary dysfunction AD Pediatric Endocrine; Genitourinary; Neurologic; Ophthalmologic Endocrine; Genitourinary Hormone replacement therapy can be effective, as individuals may have multiple pituitary insufficiency (eg, manifesting with hypothyroidism, growth hormone, gonadotropin, and cortisol deficiency) 15846561; 18628516; 18728160; 18781617; 19956411; 18854396; 19965921; 20396904; 20486942; 20494911; 21353197; 22198066; 24859618; 25293953; 25589041 OVOL2 15804 58495 Corneal dystrophy, posterior polymorphous, 1 AD Pediatric Ophthalmologic Ophthalmologic A variant in the OVOL2 promoter have been described in Corneal dystrophy, posterior polymorphous, 1 Individuals are at risk of glaucoma prior to or following corneal transplantation, and surveillance and early treatment may be beneficial 4900143; 26749309 OXCT1 8527 5019 Succinyl CoA:3-oxoacid CoA transferase deficiency AR Pediatric Biochemical Biochemical Diagnosis may allow prompt recognition and treatment of ketoacidotic episodes (eg, with IV glucose and sodium bicarbonate), which may be beneficial to reduce morbidity and mortality 4258782; 1405472; 8751852; 9521962; 10964512; 11286388; 11757586; 20652411 OXR1 15822 55074 Cerebellar hypoplasia/atrophy, epilepsy, and global developmental delay AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31785787 P2RX2 15459 22953 Deafness, autosomal dominant 41 AD N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12161595; 23345450; 24211385 P2RY12 18124 64805 Bleeding disorder, platelet-type, 8 AD/AR Pediatric Hematologic Hematologic Affected individuals can have excessive posttraumatic/postsurgical blood loss, as well as life-threatening bleeding episodes, and awareness may allow preventive measures and prompt treatment 1333302; 7706468; 11196645; 12578987; 19229056; 20966167 P3H1 19316 64175 Osteogenesis imperfecta, type VIII AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17277775; 19088120; 22281939; 22608605; 23613367 P3H2 19317 55214 Myopia, high, with cataract and vitreoretinal degeneration AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21885030; 24172257; 25469533 P4HA2 8547 8974 Myopia 25, autosomal dominant AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25741866 P4HB 8548 5034 Cole-Carpenter syndrome 1 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3794889; 25683117 P4HTM 28858 54681 Hypotonia, hyperventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities AR Pediatric Craniofacial; Neurologic; Ophthalmologic; Pulmonary Pulmonary Individuals have been described with respiratory difficulties, including bradypnea, hypoventilation, recurrent pneunomia, and sleep apnea (often requiring nighttime BiPAP), and awareness may allow early management of pulmonary issues 25078763; 30940925 PABPN1 8565 8106 Oculopharyngeal muscular dystrophy AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13997067; 13963574; 9462747; 11712939; 15725589; 15694141; 16648376; 20301305; 21647273; 21742497; 21956377; 22817818 PACS1 30032 55690 Schuss-Hoeijmakers syndrome (Mental retardation, autosomal dominant 17) AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23159249 PACS2 23794 23241 Developmental and epileptic encephalopathy 66 AD N/A N/A Cardiovascular; Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29656858 PADI3 18337 51702 Uncombable hair syndrome 1 AR N/A N/A Dermatologic General The clinical relevance of the condition is unclear 27866708 PADI6 20449 353238 Preimplantation embryonic lethality 2 AR Adult Obstetric Obstetric Genetic knowledge may be beneficial to allow reproductive-related interventions 27545678 PAFAH1B1 8574 5048 Lissencephaly 1 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9063735; 9817918; 11502906; 11754098; 12621583; 17664403; 18285425; 19050731; 19667223; 20846927; 25140959 PAH 8582 5053 Phenylketonuria; Hyperphenylalaninemia, non-PKU mild AR Pediatric Biochemical; Dermatologic; Neurologic Biochemical Dietary measures, including avoidance of aspartame, as well as adjuvant medical therapy, can be effective in preventing severe sequelae, including in preconception/prenatal circumstances 13452670; 5391176; 3008810; 3945244; 2889860; 3308176; 3819940; 2279504; 1361103; 8353710; 7885543; 8828601; 8648535; 9066890; 10472530; 10685924; 10685922; 10636975; 10683054; 11328945; 12555935; 12408183; 11999982; 12501224; 14726806; 15303001; 17935162; 20123473; 20301677; 22669364; 22841515; 22854513; 23062575; 33485801 PAK1 8590 5058 Intellectual developmental disorder with macrocephaly, seizures, and speech delay AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30290153 PAK3 8592 5063 Mental retardation, X-linked 30 XL N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8826460; 9332663; 9731525; 10946356; 12884430; 17853471; 18523455 PALB2 26144 79728 Breast cancer; Pancreatic cancer, susceptibility to 3; Fanconi anemia, complementation group N AD/AR Pediatric (Fanconi anemia, complementation group N); Adult (Breast cancer, Pancreatic cancer, susceptibility to 3) Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic The condition may include multiple congenital anomalies For Fanconi anemia, specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; surveillance for complications such as bone marrow failure is recommended; For pancreatic and breast cancer, surveillance and early treatment may be beneficial 17200668; 17287723; 17200671; 17200672; 19264984; 20858716; 22241545; 20301575; 23448497; 25099575 PALLD 17068 23022 Pancreatic cancer, susceptibility to, 1 AD Adult Oncologic Oncologic Individuals are reported to be at increased risk of pancreatic cancer, and awareness may allow early diagnosis and management 17194196 PAM16 29679 51025 Spondylometaphyseal dysplasia, Megarbane-Dagher-Melki type AR N/A N/A Cardiovascular; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18925669; 24458487; 24786642 PANK2 15894 80025 Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration; Neurodegeneration with brain iron accumulation 1 AD/AR N/A N/A Gastrointestinal; Hematologic; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 477009; 7158329; 3969211; 1447570; 1734303; 7885538; 7898702; 8944032; 11479594; 12058097; 12510040; 14638969; 15911822; 15642932; 16240131; 16437574; 16687521; 18981035; 20301663; 21286947 PANX1 8599 24145 Oocyte maturation defect 7 AD N/A N/A Obstetric General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30918116 PAPSS2 8604 9060 Brachyolmia 4 with mild epiphyseal and metaphyseal changes AR N/A N/A Endocrine; Musculoskeletal General The condition may include endocrinological manifestations such as premature pubarche Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9714015; 9771708; 19474428 PARK7 16369 11315 Parkinson disease 7, autosomal recessive early-onset AR Adult Neurologic Neurologic Response to levodopa has been documented 11462174; 11835383; 12953260; 12446870; 14638971; 16240358; 20837857; 21506293; 22956510 PARN 8609 5073 Pulmonary fibrosis and/or bone marrow failure, telomere-related 4; Dyskeratosis congenita, autosomal recessive 6 AD/AR Pediatric Dermatologic; Hematologic; Neurologic; Oncologic; Pulmonary Hematologic; Oncologic; Pulmonary In dyskeratosis congenita, the presentation many not always be classic, and individuals are at high risk for hematologic anomalies (including bone marrow failure) and malignancy, and surveillance and prompt diagnosis and treatment may be beneficial; In Aplastic anemia, surveillance and prompt treatment of aplastic anemia and bone marrow failure may reduce morbidity; For treatment related to pulmonary fibrosis, immunotherapy may be beneficial, though lung transplantation may be indicated in individuals with severe/refractory disease 25848748; 25893599; 26342108 PARS2 30563 25973 Developmental and epileptic encephalopathy 75 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25629079; 27290639; 28077841; 29410512; 29915213 PATL2 33630 197135 Oocyte maturation defect 4 AR N/A N/A Obstetric General Attempts at IVF were not described as effective Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28965844; 28965849 PAX1 8615 5075 Otofaciocervical syndrome 2 AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 23851939 PAX2 8616 5076 Isolated renal hypoplasia; Papillorenal syndrome; Focal segmental glomerulosclerosis 7 AD Pediatric Allelic with Focal segmental glomerulosclerosis 7 (AD) Audiologic/Otolaryngologic; Ophthalmologic; Renal Renal It has been suggested that variants may result in isolated renal hypoplasia without other manifestations, though on examination, many individuals have been found to have opthalmalogic anomalies The disorders may be recognizable in some individuals, but individuals are at risk of renal findings such as unrecognized vesicoureteral reflux, which can cause renal damage, and early diagnosis to allow management may be beneficial 3377002; 8589702; 7795640; 8588587; 10533062; 11093271; 11730657; 11241473;11297491; 11461952; 20301624; 20358591; 21380624; 22213154 PAX3 8617 5077 Waardenburg syndrome, type 1; Waardenburg syndrome, type 3; Craniofacial-deafness-hand syndrome AD/AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Musculoskeletal; Ophthalmologic Audiologic/Otolaryngologic The condition may be clinically recognizable, especially in individuals with one allelic form, Waardenburg syndrome, type 3, which includes features such as upper limb anomalies; A homozygous individual has been described, with very severe phenotypic effects Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 14902764; 6059431; 091186; 6859126; 1887852; 1347149; 1536170; 1347148; 1576755; 8423616; 8447316; 7981674; 8588597; 8533800; 7726174; 8664898; 9279758; 9654197; 11683776; 14556253; 12949970; 20024939; 20199465; 20478267; 20664692; 21965087 PAX4 8618 5078 Diabetes mellitus AD N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14602731; 15509590; 17130187; 16520476; 17426099; 18292467; 21263211 PAX5 8619 5079 Leukemia, acute lymphoblastic, susceptibility to, 3 AD Pediatric Oncologic Oncologic Awareness of B-ALL risk may allow surveillance and early detection and management, which may benefit morbidity and mortality; HSCT has been described 24013638 PAX6 8620 5080 Anterior segment dysgenesis 5; Cataract with late-onset corneal dystrophy; Aniridia; Aniridia, cerebellar ataxia, and mental retardation (Gillespie syndrome); Optic nerve hypoplasia; Keratitis; Foveal hypoplasia 1; Coloboma, ocular, autosomal dominant; Morning glory disc anomaly AD Pediatric Neurologic; Ophthalmologic Ophthalmologic; Pharmacogenomic Severe and difficult to treat glaucoma has been reported in many individuals with Anterior segment dysgenesis; Homozygous/compound heterozygous variants may cause severe disease, including neuroanatomic anomalies Individuals with PAX6 related eye anomalies may be recognizable, but some may also be at high risk of developing glaucoma; Agents that may contribute to glaucoma should be avoided 17948455; 14246186; 868970; 1302030; 8364574; 7951315; 8162071; 7550230; 7668281; 8640214; 9138149; 9482572; 9705283; 9931324; 11553050; 11826019; 12325030; 12721955; 15629294; 16543198; 17148041; 17417613; 17595013; 19876904; 22171686; 24290376 PAX7 8621 5081 Myopathy, congenital progressive, with scoliosis AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31092906 PAX8 8622 7849 Hypothyroidism, congenital, nongoitrous 2 AD Pediatric Endocrine; Renal Endocrine Individuals with genitourinary anomalies possibly associated with the variant have been described The untreated condition can result in severe neurological damage, and recognition can allow early medical treatment with thyroid hormone replacement can prevent such sequelae 9590296; 11502839; 11232006; 15356023; 15718293; 20718765; 20857061; 21450989; 21689132; 21976720; 22898500; 23647375 PAX9 8623 5083 Tooth agenesis, selective, 3 AD N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10615120; 11941488; 11827258; 14571272; 16333316; 16479262; 18701815; 19429910; 20485064; 20618716; 21098475; 21443745; 22058014; 22277187; 22747565 PBRM1 30064 55193 Clear cell renal cell carcinoma AD Adult Oncologic Oncologic Variants have been described as segregating with clear cell renal cell carcinoma, and awareness may be beneficial for surveillance to allow early diagnosis and management 25911086 PBX1 8632 5087 Congenital anomalies of the kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay (CAKUTHED) AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Neurologic; Renal Audiologic/Otolaryngologic; Renal Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with a variety of renal anomalies and monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function 28270404; 28566479 PC 8636 5091 Pyruvate carboxylase deficiency AR Pediatric Biochemical; Neurologic Biochemical In acute episodes, acidosis correction and glucose-containing rehydration are beneficial; Dietary (eg, with high-carbohydrate, low-protein diet, with avoidance of fasting/ketogenic diet) and medical (eg, with supplementation/substrate therapy with citrate, aspartic acid, biotin, triheptanoin) therapy may be beneficial; Liver transplant may be required in some individuals 5771860; 817914; 826106; 6422151; 6424438; 3101494; 1909777; 9585612; 12112657; 16325442; 17403843; 18676167; 19306334; 20301764 PCARE 34383 388939 Retinitis pigmentosa 54 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20398884; 20398886; 20811058; 21412943; 21792230 PCBD1 8646 5092 Hyperphenylalaninemia, BH4-deficient, D AR Pediatric Biochemical; Endocrine; Renal Renal Individuals have been treated with phenylalanine restriction and BH4 supplementation, but such interventions may not be indicated In addition to other findings, patients may develop hypomagnesemia with renal magnesium loss, and awareness may allow medical management (magnesium supplementation), which has been reported as clinically beneficial 8352282; 9585615; 9760199; 24204001; 24848070 PCCA 8653 5095 Propionic acidemia AR Pediatric Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Hematologic; Neurologic Biochemical; Cardiovascular In acute episodes, acidosis and hypoglycemia correction, with IV carnitine are beneficial (hemodialysis may be required); Dietary (including protein restriction, to decrease propiogenic substrates) and medical (eg, l-carnitine, metronidazole, N-carbamoylglutamate) therapy may be beneficial; Liver transplant may be required in some individuals; Fasting should be avoided, and care should be taken in the setting of acute stressors; Individuals are at risk for manifestations such as cardiovascular aberrations, and surveillance may be beneficial 4815259; 10502773; 17051315; 19157943; 20301313; 22033733; 22593918 ; 23053474; 30879957 PCCB 8654 5096 Propionic acidemia AR Pediatric Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Hematologic; Neurologic Biochemical; Cardiovascular In acute episodes, acidosis and hypoglycemia correction, with IV carnitine are beneficial (hemodialysis may be required); Dietary (including protein restriction, to decrease propiogenic substrates) and medical (eg, l-carnitine, metronidazole, N-carbamoylglutamate) therapy may be beneficial; Liver transplant may be required in some individuals; Fasting should be avoided, and care should be taken in the setting of acute stressors; Individuals are at risk for manifestations such as cardiovascular aberrations, and surveillance may be beneficial 10502773; 17051315; 19238581; 20301313; 22593918; 22033733; 23053474; 30879957 PCDH12 8657 51294 Microcephaly, seizures, spasticity, and brain calcifications (MISSBC) AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27164683; 28804758 PCDH15 14674 65217 Deafness, autosomal recessive 23; Usher syndrome, type 1F; Usher syndrome, type 1D/F, digenic AR/Digenic Pediatric Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic Inheritance can be digenic, involving CDH23 Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 11398101; 14570705; 15537665; 17653769; 18719945; 19107147 PCDH19 14270 57526 Epileptic encephalopathy, early infantile, 9 XL N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18469813; 19214208; 19752159; 20830798; 20713952; 21519002; 21777234; 22050978; 22267240; 22633638; 22848613; 22949144 PCGF2 12929 7703 Turnpenny-Fry syndrome AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25533962; 30343942 PCK1 8724 5105 Phosphoenolpyruvate carboxykinase-1, cytosolic, deficiency AR Pediatric Biochemical Biochemical Individuals have been described with manifestations such as early-onset hypoglycemia, and awareness can allow prompt treatment of acute episodes as well as longer-term dietary management (low-fat, high-carbohydrate diet with frequent feedings) 24863970; 26971250; 28216384 PCNA 8729 5111 Ataxia-telangiectasia-like disorder 2 AR Pediatric Dermatologic; Neurologic; Oncologic; Ophthalmologic Oncologic An individual has been described with evidence of predisposition to malignancy related to sun exposure, and preventive measures and surveillance may allow prevent oncologic disease and allow early diagnosis and management 24911150 PCNT 16068 5116 Microcephalic osteodysplastic primordial dwarfism, type II AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Individuals may have cerebral neurovascular anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7201238; 9800906; 9800908; 12400072; 12210304; 15368497; 15372530; 18157127; 18174396; 20358609; 19643772; 21567919 PCSK1 8743 5122 Proprotein convertase 1/3 deficiency AD N/A N/A Endocrine; Gastrointestinal Gastrointestinal Endocrinologic interventions can allow induction of secondary sex characteristic and reproduction Presentations may be diverse, and interventions such as early parenteral nutrition may be necessary 7477119; 9207799; 14617756; 17595246 PCSK9 20001 255738 Hypercholesterolemia, familial, 3 AD Pediatric Cardiovascular Cardiovascular Interventions to maintain lipid profiles at a more desirable level can decrease morbidity/mortality, such as relates to CAD 10205269; 10764678; 12730697; 15166014; 14727156; 14727179; 15654334; 15772090; 16554528; 16909389; 18354102; 22683120 PCYT1A 8754 5130 Spondylometaphyseal dysplasia with cone-rod dystrophy AR N/A N/A Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24387990; 24387991 PCYT2 8756 5833 Spastic paraplegia 82, autosomal recessive AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31637422 PDCD10 8761 11235 Cerebral cavernous malformations 3 AD Pediatric Cardiovascular; Neurologic Cardiovascular; Neurologic; Pharmacogenomic Surveillance measures (eg, spinal cord MRI, annual brain gradient echo or susceptibility-weighted imaging) has been advocated; Agents that increase risk of hemorrhage should be avoided (eg, aspirin, NSAIDs, heparin, warfarin) 15543491; 16380626; 18060436; 19088123; 20301470; 21029238; 23485406; 23595507; 23663874 PDE10A 8772 10846 Striatal degeneration, autosomal dominant 2 AD/AR Pediatric Allelic with Infantile-onset dyskinesia (AR) Neurologic Neurologic In Striatal degeneration, autosomal dominant 2, treatment with levodopa has been described as beneficial in some individuals who developed Parkinsonism 27058446; 27058447 PDE11A 8773 50940 Pigmented nodular adrenocortical disease, primary, 2 AD Pediatric Endocrine Endocrine Treatment of adrenal disease (eg, potentially including surgical intervention) may be beneficial 16767104; 20351491; 21115159 PDE1C 8776 5137 Deafness, autosomal dominant 74 AD N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29860631 PDE2A 8777 5138 Intellectual developmental disorder with paroxysmal dyskinesia or seizures AR Pediatric Craniofacial; Neurologic Neurologic While the seizures have been desribed as refractory to antieepileptic mediactions, medical management (eg, with vigabatrin) has been reported as transiently improving the neurologic abnormalities in an individual, and deep brain neurostimulation has been described as resulting in clinical improvement of the movement disorder 29392776; 32196122; 32467598 PDE3A 8778 5139 Hypertension with brachydactyly AD Pediatric Cardiovascular; Musculoskeletal Cardiovascular Individuals have been described as suffering from death by stroke by age 50 when untreated, and awareness may allow early management of hypertension, which has been described as having onset in childhood 4774535; 9415685; 25961942 PDE4D 8783 5144 Acrodysostosis 2, with or without hormone resistance AD Pediatric Cardiovascular;Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic Cardiovascular; Endocrine Individuals have been described with cardiovascular anomalies, including deep vein thrombosis, and awareness may allow early recognition and treatment; Individuals have been described with endocrine anomalies, including parathyroid hormone resistance and hypogonadism, and awareness may allow surveillance and early medical interventions 11200992; 22464252; 22464250; 22464252; 23033274; 24203977 PDE6A 8785 5145 Retinitis pigmentosa 43 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7493036; 18723146; 21039428 PDE6B 8786 5158 Night blindness, congenital stationary, autosomal dominant 2; Joubert syndrome 22; Retinitis pigmentosa 40 AD/AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8394174; 8075643; 7599633; 17044014; 18854872; 20655036; 24166846; 30423442 PDE6C 8787 5146 Cone dystrophy 4 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19887631; 19615668 PDE6D 8788 5147 Joubert syndrome 22 AR N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24166846 PDE6G 8789 5148 Retinitis pigmentosa 57 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20655036 PDE6H 8790 5149 Achromatopsia 6; Retinal cone dystrophy 3A AD/AR N/A N/A Ophthalmologic General Inheritance is unclear, and may involve recessive model or incomplete penetrance Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15629837; 22901948 PDE8B 8794 8622 Pigmented nodular adrenocortical disease, primary, 3 AD Pediatric Allelic with Striatal degeneration, autosomal dominant 1 (AD) Endocrine; Neurologic Endocrine Treatment of adrenal disease (eg, potentially including surgical intervention) may be beneficial 15210883; 18272904; 21115159; 20085714; 20373981 PDGFB 8800 5155 Basal ganglia calcification, idiopathic, 5 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23913003 PDGFRA 8803 5156 Gastrointestinal stromal tumor; GIST-plus syndrome AD Adult Craniofacial; Dental; Dermatologic; Musculoskeletal; Oncologic Oncologic Individuals with Gastrointestinal stromal tumor may be at high risk for the development of gastrointestinal stromal tumor, and surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality; Individuals with GIST-plus syndrome may be at risk of multiple mesenchymal tumors of the gastrointestinal tract, and surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality 14699510; 17087943; 17566086; 25975287; 29486293 PDGFRB 8804 5159 Basal ganglia calcification, idiopathic, 4; Kosaki overgrowth syndrome; Myofibromatosis, infantile 1; Premature aging syndrome, Penttinen type AD Pediatric Allelic with Basal ganglia calcification, idiopathic, 4 (AD); Kosaki overgrowth syndrome (AD); Premature aging syndrome, Penttinen type (AD) Craniofacial; Dermatologic; Musculoskeletal; Neurologic Oncologic Myofibromatosis, infantile 1 involves benign tumors affecting the skin, muscle, bone, and viscera, and awareness of visceral neoplasms may be beneficial in order to diagnose and manage lesions 9056558; 23255827; 23720404; 23731537; 23731542; 25454926; 26279204 PDHA1 8806 5160 Pyruvate dehydrogenase E1-alpha deficiency; Leigh syndrome, X-linked XL Pediatric Biochemical; Neurologic Biochemical Therapy may not be effective in many individuals, but dietary (ketogenic diet) and medical (eg, thiamine) therapy may be beneficial 5786203; 4343503; 824610; 413346; 4050860; 2537010; 1293379; 1301207; 7692352; 7880337; 7808831; 8032855; 8199595; 8498846; 9727848; 10486093; 12379317; 12621116; 15138885; 18197404; 18398624; 18504677; 19517265; 19639391; 20002461; 20301764; 20462777; 21470495; 21914562; 23021068 PDHB 8808 5162 Pyruvate dehydrogensae E1-beta deficiency AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15138885; 21914562 PDHX 21350 8050 Pyruvate dehydrogenase E3-binding protein deficiency AR Pediatric Biochemical; Neurologic Biochemical Medical and dietary treatment (eg, ketogenic diet) may be beneficial 2112155; 8229524; 8584393; 9399911; 9501264; 10590436; 11935326; 12208141; 12557299; 15303005; 16566017; 16843025; 17152059; 20002125; 21914562; 21937992; 22766002; 25087164 PDK3 8811 5165 Charcot-Marie-Tooth disease, X-linked, dominant,6 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23297365 PDP1 9279 54704 Pyruvate dehydrogenase phosphatase deficiency AR N/A N/A Biochemical; Neurologic General As with other conditions that involve seizures, optimal seizure control is important, and may be influenced by knowing the molecular cause Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15855260; 19184109; 31392110 PDSS1 17759 23590 Coenzyme Q10 deficiency 2 AR Pediatric Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Renal Biochemical There can be a wide range of manifestations, and in some individuals, treatment with Coenzyme Q10 supplementation can be beneficial 17332895; 22231380 PDSS2 23041 57107 Coenzyme Q10 deficiency 3 AR Pediatric Biochemical; Neurologic; Renal Biochemical Treatment with Coenzyme Q10 supplementation may be beneficial 17186472; 22231380 PDX1 6107 3651 Pancreatic agenesis 1; Neonatal diabetes mellitus AR Pediatric Allelic with Maturity-onset diabetes of the young, type 4 (AD); Lactic acidemia due to PDX1 deficiency (AR) Biochemical; Endocrine; Gastrointestinal; Neurologic Endocrine; Gastrointestinal Individuals may manifest in infancy with findings including intrauterine growth retardation, postnatal growth deficiency, and signs of diabetes mellitus (eg, hyperglycemia, glycosuria), as well as severe dehydration, and recognition can allow preventive measures related to potential sequelae, surveillance (eg, with blood glucose monitoring as well as surveillance for other common sequelae of diabetes mellitus affecting systems such as the renal and ophthalmogic systems); In the case of an acute diabetic crisis, rapid treatment (eg, with rehydration and IV insulin, transitioning to SQ insulin when stable) is indicated, though rapid-acting and (non-continuous) short-acting insulin preparations may result in severe hypoglycemia in young patients; Due to exocrine (as well as endocrine) pancreatic insufficiency, some individuals may benefit from enzymatic replacement 8506821; 8988180; 9326926; 9399911; 9649577; 10545531; 10545530; 10720084; 11575290; 11935326; 12970316; 19496967; 20009086; 20301620; 20546293; 20621032; 21521318; 21937992; 22124438; 23320570; 25087164 PDXK 8819 8566 Hereditary motor and sensory neuropathy, type VIC, with optic atrophy (Charcot-Marie-Tooth disease, type 6C) AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31187503 PDYN 8820 5173 Spinocerebellar ataxia 23 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15306549; 21035104 PDZD7 26257 79955 Deafness, autosomal recessive 57; Usher syndrome, type IIC AR/Digenic Pediatric Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic For Usher syndrome, type IIc, digenic inheritance (with GRP98) has been described Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 19028668; 20440071; 26416264; 26849169; 29048736 PEPD 8840 5184 Prolidase deficiency AR Pediatric Allergy/Immunology/Infectious; Biochemical; Craniofacial; Dermatologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Individuals may have a number of manifestations, including frequent and severe respiratory and other infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 4828441; 874681; 908977; 7095220; 6727550; 1972707; 8198124; 8900231; 12384772; 16470701; 18340504; 19308961; 19937054 PER2 8846 8864 Advanced sleep phase syndrome, familial,1 AD N/A N/A Neurologic General The clinical relevance of the condition is unclear 15800623 PER3 8847 8863 Advanced sleep phase syndrome, familial, 3 AD N/A N/A Neurologic General The clinical relevance of the condition is unclear 27001847 PERCC1 52293 105371045 Diarrhea 11, malabsorptive, congenital AR Pediatric Gastrointestinal Gastrointestinal Noncoding variants in what has been designated as an "intestine critical region" (ICR) affect expression of the PERCC1 gene The condition can involve severe and early-onset diarrhea, and awareness may help with management (eg, via parenteral nutrition, which has been described as necessary) 31217582 PERP 17637 64065 Olmsted syndrome 2; Erythrokeratodermia variabilis et progressiva 7 AD/AR N/A N/A Dental; Dematologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30321533; 31361044; 31898316 PET100 40038 100131801 Mitochondrial complex IV deficiency, nuclear type 12 AR N/A N/A Biochemical; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24462369 PET117 40045 100303755 Mitochondrial complex IV deficiency, nuclear type 19 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28386624 PEX1 8850 5189 Heimler syndrome 1 AR Pediatric Allelic with Peroxisome biogenesis factor disorder 1A (AR); Peroxisome biogenesis factor disorder 1B (AR) Audiologic/Otolaryngologic; Biochemical; Craniofacial; Dental; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal Audiologic/Otolaryngologic The conditions can involve multiple congenital anomalies Heimler syndrome 1, representing a mild peroxisomal biogenesis disorder, includes sensorineural hearing loss among other features, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 2063923; 10636745; 9398848; 9398847; 9817926; 9539740; 10447258; 11389485; 12402331; 12032265; 15098231; 16086329; 16088892; 16141001; 20212125; 21844578; 22378672; 26387595 PEX10 8851 5192 Peroxisome biogenesis disorder 6A (Zellweger syndrome); Peroxisome biogenesis disorder 6B AR N/A N/A Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9700193; 9683594; 12794690; 10862081; 17041890; 19127411; 20695019 PEX11B 8853 8799 Peroxisome biogenesis factor disorder 14B AR N/A N/A Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22581968 PEX12 8854 5193 Peroxisome biogenesis disorder 3A; Peroxisome biogenesis factor disorder 3B AR N/A N/A Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9090384; 9354782; 9632816; 9792857; 14571262; 17041890; 17534573 PEX13 8855 5194 Peroxisome biogenesis disorder 11A (Zellweger syndrome); Peroxisome biogenesis disorder 11B AR N/A N/A Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9480815; 10441568; 10332040; 17041890; 19449432 PEX14 8856 5195 Peroxisome biogenesis factor disorder 14; Zellweger syndrome AR N/A N/A Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15146459; 18285423; 21686775 PEX16 8857 9409 Peroxisome biogenesis factor disorder 8A (Zellweger syndrome); Peroxisome biogenesis disorder 8B AR N/A N/A Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9837814; 11890679; 20647552 PEX19 9713 5824 Peroxisome biogenesis disorder, 19; Zellweger syndrome AR N/A N/A Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9727033; 10051604; 20683989 PEX2 9717 5828 Peroxisome biogenesis disorder 5A; Peroxisome biogenesis disorder 5B AR N/A N/A Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1546315; 7541833; 10528859; 14630978; 17041890; 21392394 PEX26 22965 55670 Peroxisome biogenesis disorder 7A; Peroxisome biogenesis disorder 7B; Adrenoleukodystrophy, neonatal; Refsum disease, infantile AR N/A N/A Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12851857; 12717447; 15542397; 15858711; 19105186 PEX3 8858 8504 Peroxisome biogenesis factor disorder 3; Peroxisome biogenesis disorder 10A (Zellweger); Peroxisome biogenesis disorder 10B AR N/A N/A Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10968777; 10679269; 10942428; 27557811 PEX5 9719 5830 Peroxisome biogenesis disorder 2A (Zellweger syndrome); Peroxisome biogenesis disorder 2B; Rhizomelic chondrodysplasia punctata, type 5 AR N/A N/A Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7719337; 26220973 PEX6 8859 5190 Heimler syndrome 2 (Peroxisome biogenesis disorder 4C) AR Pediatric Allelic with Peroxisome biogenesis disorder 4A (AR); Peroxisome biogenesis disorder 4B (AR) Audiologic/Otolaryngologic; Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal Audiologic/Otolaryngologic The conditions can involve multiple congenital anomalies Heimler syndrome 2, representing a mild peroxisomal biogenesis disorder, includes sensorineural hearing loss among other features, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 8940266; 8670792; 10408779; 11355018; 16530715; 17041890; 19877282; 21937992; 22894767; 26387595 PEX7 8860 5191 Refsum disease AR Pediatric Allelic with Peroxisome biogenesis disorder 9B (AR); Rhizomelic chondrodysplasia punctata, type 1 (AR) Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic Biochemical Dietary measures (eg, phytanic acid restriction, high calorie diet) can help with dermatologic and neurologic manifestations; Surveillance and medical carefor cardiac arrhythmias and cardiomyopathy can reduce morbidity/mortality; Plasmapheresis/lipid apheresis may be used; Fasting and ibuprofen should be avoided 18140089; 13045168; 4159604; 85164; 6160883; 2452736; 7541833; 9090381; 9090382; 9090383; 12325024; 11781871; 12522768; 14974078; 17325280; 20301527; 23352163 PFKM 8877 5213 Glycogen storage disease VII AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic; Renal Cardiovascular; Musculoskeletal; Renal There is a wide range of types and severity, but avoidance of excessive exercise may be beneficial in order to avoid renal sequale; Surveillance for cardiovascular complications (eg, cardiac hypertrophy) may allow early detection and treatment 14339001; 4228297; 4228753; 4258222; 6444532; 6444721; 6943439; 6220601; 2945125; 2960695; 2140573; 1533013; 8444874; 8037209; 7513946; 7550225; 7479776; 8889589; 9389749; 22133655; 22364848 PFN1 8881 5216 Amyotrophic lateral sclerosis 18 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22801503; 23141414 PGAM2 8889 5224 Glycogen storage disease X AR Pediatric Biochemical; Musculoskeletal; Renal Renal Preventive measures to reduce the chance of severe sequelae can be beneficial, as individuals can present with exercise intolerance, and renal failure has been described 6283419; 6262916; 6308514; 8447317; 10545043; 19273759 PGAP1 25712 80055 Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24784135 PGAP2 17893 27315 Hyperphosphatasia with mental retardation syndrome 3 AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21629298; 21643797; 23561846; 23561847 PGAP3 23719 93210 Hyperphosphatasia with mental retardation syndrome 4 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22315194; 24439110; 29620724; 30217754; 30345601 PGK1 8896 5230 Phosphoglycerate kinase 1 deficiency XL Pediatric Hematologic; Musculoskeletal; Neurologic; Renal Hematologic; Musculoskeletal; Renal Individuals (males by report) may have partially transfusion-dependent anemia, as well as hemolytic crises requiring measures such as exchange transfusion; Rhabdomyolysis leading to acute renal failure has also been reported, and 5764452; 6933565; 7082849; 3605066; 2715616; 1547346; 7577653; 9512313; 16412025; 16567715; 17222195; 22705348 PGM1 8905 5236 19625727; 22492991; 24499211; 28617415; 33342467 AR Pediatric Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Renal Biochemical; Cardiovascular; Hematologic; Pharmacogenomic; Renal Treatment with galactose has been described as beneficial (including related to individuals with reported hypogonadotropic hypogonadism as well as parameters related to hepatic function); Individuals may have exercise-induced intolerance with episodic rhabdomyolysis, and precautions may decrease associated morbidity; Individuals have been described with dilated cardiomyopathy, and surveillance may allow early medical management; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery; Hepatic-metabolized agents should be avoided; Cardiac transplant has been described 19625727; 22492991; 24499211; 28617415 PGM3 8907 5238 Immunodeficiency 23 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Oncologic Allergy/Immunology/Infectious; Oncologic Individuals are susceptible to recurrent and severe viral, bacterial, and fungal infections (as well as sequelae such as EBV-related lymphoma), and and prophylaxis, as well as prompt and aggressive treatment of infections may be beneficial 14981714; 24589341; 24698316; 24931394 PHACTR1 20990 221692 Developmental and epileptic encephalopathy 70 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23033978; 30256902 PHC1 3182 1911 Microcephaly 11, primary, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23418308 PHEX 8918 5251 Hypophosphatemic rickets, X-linked dominant XL Pediatric Cardiovascular; Dental; Musculoskeletal; Neurologic; Renal Cardiovascular; Renal Frequent oral administration of phosphate and high-dose calcitriol can be beneficial for bowing of long bones during growth and for pain; Diagnosis can help avoid therapies that may result in adverse sequelae; Due to reported cardiovascular manifestations (eg, hypertension, left ventricular hypertrophy), surveillance may allow early diagnosis and management 4305189; 4333173; 188828; 2984933; 3839245; 2571821; 1660099; 1660098; 1414477; 1464657; 7550339; 9106524; 9253316; 9768646; 10874297; 12915641; 14769584; 16055933; 18252791; 21050253; 21524226; 22319799 PHF21A 24156 51317 Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30487643; 31649809 PHF6 18145 84295 Borjeson-Forssman-Lehmann syndrome XL N/A N/A Craniofacial; Endocrine; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13871358; 4465467; 12415272; 15241480; 14756673; 15994862; 16912705; 19264739; 22190899; 23906836 PHF8 20672 23133 Siderius X-linked mental retardation syndrome XL N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10398231; 16199551; 17594395; 17661819; 23092983 PHGDH 8923 26227 Phosphoglycerate dehydrogenase deficiency AR Pediatric Allelic with Neu-Laxova syndrome 1 (AR) Biochemical; Craniofacial; Dermatologic; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary Biochemical Neu-Laxova syndrome can involve multiple congenital anomalies Amino acid therapy (eg, with L-serine, glycine) has been reported as beneficial for at least some clinical parameters, especially if early treatment is inititiated (reports include benefits to prenatal treatment) 8739971 ; 8758134; 11055895; 12118526; 15610810; 16763900; 19235232; 20196394; 21113737; 24836451; 28135894 PHIP 15673 55023 Chung-Jansen synrome (Developmental delay, intellectual disability, obesity, and dysmorphic features) AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23033978; 27900362; 29209020 PHKA1 8925 5255 Glycogen storage disease, type IXd XL Pediatric Biochemical; Musculoskeletal; Renal Pharmacogenomic; Musculoskeletal; Renal Individuals should avoid circumstances such as vigorous exercise as well as certain medications (eg, succinylcholine, statins) due to risk of rhabdomyolysis 2252364; 7874115; 9731190; 12825073; 21634085 PHKA2 8926 5256 The conditions can include manifestations such as hypoglycemia, ketosis, and growth retardation, and recommendations for care include laboratory-based monitoring (eg, including liver function tests, glucose, and ketones), radiological monitoring (abdominal imaging), and nutritional recommendations and avoidance of certain medications in order to help improve metabolic to control and prevent the primary complications; Specific care during pregnancy has been recommended XL Pediatric Biochemical; Gastrointestinal; Musculoskeletal; Neurologic Biochemical; Gastrointestinal The conditions can include manifestations suc has hypoglycemia, ketosis, and growth retardation, and recommendations for care include laboratory-based monitoring (eg, including liver function tests, glucose, and ketones), radiological monitoring (abdominal imaging), and nutritional recommendations and avoidance of certain medications in order to help improve metabolic to control and prevent the primary complications; Specific care during pregnancy has been recommended 5306139; 4518931; 280544; 2303074; 7711737; 7847371; 8733134; 9600238; 9835437; 9870210; 10330341; 11286390; 12809646; 12862311; 16354226; 17581768; 17689125; 19856867; 21131218; 21646031; 21634085; 21844581; 21857251; 21911307; 24055370; 25266922; 30659246; 33317799 PHKB 8927 5257 Glycogen storage disease IXb AR Pediatric Biochemical; Gastrointestinal; Musculoskeletal Biochemical; Gastrointestinal; Musculoskeletal Dietary measures to prevent sequelae (eg, frequent feedings high in complex carbohydrates/protein), as well as specific measures if hypoglycemia/ketosis is present (eg, Polycose, fruit juice, IV glucose) can be beneficial; Surveillance liver ultrasonography is indicated in childhood; Certain diets and medications should be avoided (eg, copious simple sugars, sulfonylureas, alcohol, succinylcholine, statins), as well as vigorous exercise 6938920; 6422139; 9215682; 17689125; 21646031; 21634085; 25266922; 33317799 PHKG2 8931 5261 Glycogen storage disease IXc AR Pediatric Biochemical; Gastrointestinal; Musculoskeletal; Neurologic Biochemical; Gastrointestinal In Liver PhK deficiency, dietary management can prevent and treat hypoglycemia during acute and stable periods; Specific hepatic surveillance is indicated in childhood; Other interventions have also been reported as beneficial 6952760; 6962066; 8896567; 9245685; 9384616; 10905889; 12930917; 17689125; 21646031; 21634085; 24102521; 25266922; 33317799 PHOX2A 691 401 Fibrosis of extraocular muscles, congenital, 2 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11600883 PHOX2B 9143 8929 Central hypoventilation syndrome, congenital; Neuroblastoma with Hirschsprung disease; Neuroblastoma, susceptiblity to, 2 AD Pediatric Gastrointestinal; Neurologic; Oncologic Neurologic; Oncologic Individuals are also at risk of additional autonomic nervous system anomalies including Hirschsprung disease In Central hypoventilation syndrome, congenital, early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality; In Neuroblastoma, susceptibility to, 2 and Neuroblastoma with Hirschsprung disease, surveillance and/or awareness of cancer risk (involving the sympathetic nervous system) may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality 10390427; 12640453; 14566559; 15024693; 16873766; 16691592; 20301600; 32073407 PHYH 8940 5264 Refsum disease AR Pediatric Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic Biochemical; Cardiovascular; Pharmacogenomic Dietary measures (high calorie diet with phytanic acid restriction) may be beneficial; Surveillance can allow early diagnosis and treatment of cardiac manifestsations (eg, cardiac arrhythmias, cardiomyopathy); Plasmapheresis/lipid apheresis may be indicated in severe situations; Certain agents/circumstances (eg, fasting, ibuprofen) should be avoided 13045168; 18140089; 4159604; 85164; 6160883; 2452736; 9326939; 9326940; 10767344; 17905308; 20301527; 20547622; 22156782 PHYKPL 28249 85007 Phosphohydroxylysinuria AR N/A N/A Biochemical General Individuals have been described with multiple phenotypes, but the overall consequences are unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2387074; 23242558 PI4KA 8983 5297 Perisylvian polymicrogyria, cerebellar hypoplasia, and arthrogryposis AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25855803 PIBF1 23352 10464 Joubert syndrome 33 AR N/A N/A Craniofacial; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26167768; 29695797; 30858804 PIEZO1 28993 9780 Dehydrated hereditary stomatocytosis 1 with or without pseudohyperkalemia and/or perinatal edema AD Pediatric Allelic with Lymphatic malformation 6 (AR) Dermatologic; Hematologic Hematologic The condition is highly variable, and can involve moderately symptomatic hemolysis, severe iron overload requiring hepatic transplantation, and life-threatening thromboembolic disease after splenectomy, and awareness may allow early medical management 22529292; 23479567; 23695678; 26333996 PIEZO2 26270 63895 Arthrogryposis, distal, type 3; Arthrogryposis, distal, type 5; Marden-Walker syndrome; Arthrogryposis, distal, with impaired proprioception and touch AD/AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23487782; 24726473; 27607563; 27653382 PIGA 8957 5277 Multiple congenital anomalies-hypotonia-seizures syndrome 2 XL N/A N/A Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22305531 PIGB 8959 9488 Developmental and epileptic encephalopathy 80 AR N/A N/A Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31256876 PIGC 8960 5279 Glycosylphosphatidylinositol biosynthesis defect 16 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27694521 PIGG 25985 54872 Mental retardation, autosomal recessive 53 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26996948 PIGH 8964 5283 Glycosylphosphatidylinositol biosynthesis defect 17 AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29573052; 29603516 PIGK 8965 10026 Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31353022 PIGL 8966 9487 CHIME syndrome AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Neurologic; Ophthalmologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22444671 PIGM 18858 93183 Glycosylphosphatidylinositol biosynthesis defect 1 AR Pediatric Biochemical; Hematologic; Neurologic Biochemical; Hematologic; Neurologic; Pharmacogenomic Medical treatment may be beneficial (eg, prophylactic oral anticoagulants to prevent thrombosis; sodium phenylbutyrate for seizure control); Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery; Hepatic-metabolized agents should be avoided 16767100; 17442906; 19168132; 31445883 PIGN 8967 23556 Multiple congenital anomalies-hypotonia-seizures syndrome 1 AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Genitourinary; Neurologic; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21493957; 24253414 PIGO 23215 84720 Hyperphosphatasia with mental retardation syndrome 2 AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22683086 PIGP 3046 51227 Developmental and epileptic encephalopathy 55 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28334793 PIGQ 14135 9091 Multiple congenital anomalies-hypotonia-seizures syndrome 4 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24463883; 25558065; 31148362 PIGS 14937 94005 Developmental and epileptic encephalopathy 95 AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic Neurologic Among other manifestations, individuals may have difficult-to-control seizures, and management with oral pyridoxine has been described as beneficial 30269814; 33410539 PIGT 14938 51604 Multiple congenital anomalies-hypotonia-seizures syndrome 3 AR N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23636107; 24906948; 25943031; 28728837 PIGU 15791 128869 Neurodevelopmental disorder with brain anomalies, seizures, and scoliosis AR N/A N/A Biochemical; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31353022 PIGV 26031 55650 Hyperphosphatasia with mental retardation syndrome 1 AR N/A N/A Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5465362; 1724113; 16638507; 17351347; 20080219; 20802478; 20578257; 21739589; 22315194 PIGW 23213 284098 Glycosylphosphatidylinositol biosynthesis defect 11 AR N/A N/A Craniofacial; Gastrointestinal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24367057 PIGY 28213 84992 Hyperphosphatasia with mental retardation syndrome 6 AR N/A N/A Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26293662 PIK3C2A 8971 5286 Oculoskeletodental syndrome AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic Audiologic/Otolaryngologic; Ophthalmologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; The condition can include secondary glaucoma, and awareness may allow prompt diagnosis and management 31034465 PIK3CA 8975 5290 Cowden syndrome 5 AD Adult Dermatologic; Endocrine; Oncologic Oncologic Individuals have been reported with a variety of types of cancer, including breast, thyroid, renal, and endometrial cancer, and surveillance and awareness may allow early detection and management of neoplastic disease 23246288 PIK3CD 8977 5293 Immunodeficiency 14A, autosomal dominant; Immunodeficiency 14B, autosomal recessive AD/AR Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic Biallelic variants, along with biallelic variants in KNSTRN, have been described as causing Roifman-Chitayat syndrome, digenic Individuals with Immunodeficiency 14A and Immunodeficiency 14B have been described as having a primary immunodeficiency, with susceptibility to respiratory and other infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals with Immunodeficiency 14A, autosomal dominant have been described as developing lymphoma, and awareness may allow early recognition and management 24136356; 24165795; 24610295; 30040974; 30336224 PIK3R1 8979 5295 Agammaglobulinemia 7, autosomal recessive; Immunodeficiency 36 AR Pediatric Allelic with SHORT syndrome (AD) Allergy/Immunology/Infectious; Craniofacial; Dental; Endocrine; Musculoskeletal; Ophthalmologic Allergy/Immunology/Infectious Individuals may demonstrate susceptibility to severe infections (in addition to autoimmune-type sequelae in some conditions) and prophylactic measures (eg, including IVIG administration), as well as early and aggressive treatment of infections, has been reported as being beneficial 7705412; 22351933; 23810378; 23810382; 25133428 PIK3R2 8980 5296 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17675034; 22729224; 23745724 PIK3R5 30035 23533 Ataxia-oculomotor apraxia 3 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22065524 PIKFYVE 23785 200576 Corneal fleck dystrophy AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15902656; 23288988; 26396486 PINK1 14581 65018 Pediatric AR N/A Neurologic Neurologic Heterozygotes may display more subtle signs of disease, and have been described as susceptibility alleles Response to levodopa has been documented 15505170; 15349870; 15087508; 15955954; 15970950; 16969854; 17030667; 16769864; 16966503; 16632486; 18685134; 18541801; 21784538; 22581678; 22956510 PIP5K1C 8996 23396 Lethal congenital contractural syndrome 3 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17701898 PITPNM3 21043 83394 Cone-rod dystrophy 5 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8586428; 17377520; 18188949; 22405330 PITX1 9004 5307 Clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly; Liebenberg syndrome AD N/A N/A Craniofacial; Musculoskeletal General Liebenberg syndrome may be caused by abornmal gene expression due to gene-regulatory anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18950742; 21775501; 22258522; 23022097 PITX2 9005 5308 Axenfeld-Rieger syndrome, type 1; Ring dermoid of cornea; Anterior segment dysgenesis 4; Anterior segment dysgenesis 5 AD Adult Dental; Ophthalmologic Ophthalmologic; Pharmacogenomic Severe and difficult to treat glaucoma has been reported in many individuals with Anterior segment dysgenesis Individuals have a high risk of developing glaucoma, but treatment may not be effective in the majority of cases; Agents that may contribute to glaucoma should be avoided 4953922; 6029228; 6871144; 2594319; 7581385; 8944018; 9437321; 9618168; 10051017; 11004268; 11929847; 12015277; 15591271; 17197537; 22569110 PITX3 9006 5309 Cataract 11, multiple types; Cataract 11, syndromic; Anterior segment dysgenesis 1 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6801987; 9620774; 10361984; 15286169; 16565358; 17888164; 18989383; 21633712; 22223473 PJVK 29502 494513 Deafness, autosomal recessive 59 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 17718865; 17373699; 7301963; 17329413 PKD1 9008 5310 Polycystic kidney disease 1 with or without polycystic liver disease AD Pediatric Cardiovascular; Gastrointestinal; Renal Cardiovascular; Gastrointestinal; Pharmacogenomic; Renal A number of manifestations can benefit from surveillance and early treatment, including surveillance for cardiovascular findings such as intracranial aneurysms and aortic dilation can allow early detection and treatment; Treatment for hypertension is frequently required (eg, with ACE inhibitors/angiotensin II receptor blockers); A number of agents should be avoided, including nephrotoxic agents, estrogens, smoking and agents that increase renal cysts; Additional considerations related to hepatic and other cyst-related manifestations may be beneficial 13723091; 5641158; 6102642; 6766288; 6835317; 3419455; 2198396; 1670785; 1513348; 1583643; 8004675; 7633405; 9650770; 11359016; 11134267; 11752048; 12842373; 12900587; 15458452; 15086900; 12631134; 14581387; 15034105; 14531813; 17699192; 16354965; 17699202; 16707749; 17035604; 16775462; 18299682; 17699395; 17533013; 17434405; 19443633; 19470662; 20301424; 20219616; 21551026; 21544064; 21333426 PKD1L1 18053 168507 Heterotaxy, visceral, 8, autosomal AR N/A N/A Cardiovascular; Gastrointestinal; Renal General The ocndition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27616478 PKD2 9009 5311 Polycystic kidney disease 2 with or without polycystic liver disease AD Pediatric Cardiovascular; Gastrointestinal; Renal Cardiovascular; Gastrointestinal; Pharmacogenomic; Renal A number of manifestations can benefit from surveillance and early treatment, including surveillance for cardiovascular findings such as intracranial aneurysms and aortic dilation can allow early detection and treatment; Treatment for hypertension is frequently required (eg, with ACE inhibitors/angiotensin II receptor blockers); A number of agents should be avoided, including nephrotoxic agents, estrogens, smoking and agents that increase renal cysts; Additional considerations related to hepatic and other cyst-related manifestations may be beneficial 8650545; 9402976; 9326320; 9773786; 9573526; 11156533; 11752048; 17699192; 17699202; 16707749; 17035604; 19443633; 20301424; 20219616; 21544064; 21551026 PKDCC 25123 91461 Rhizomelic limb shortening with dysmorphic features AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30478137 PKHD1 9016 5314 Polycystic kidney disease 4 with or without polycystic liver disease AR Pediatric Allergy/Immunology/Infectious; Endocrine; Gastrointestinal; Renal Allergy/Immunology/Infectious; Gastrointestinal; Pulmonary; Pharmacogenomic; Renal Initially, neonates may require interventions related to compromises in respiratory and renal function, including surgical interventions and dialysis as necessary (renal transplant may be indicated as well); Surveillance and interventions for complications related to systemic and portal hypertension can be beneficial; Medical treatment (eg, with ACE inhibitors or ARBs) can be beneficial; Other interventions, such as nutritional and endocrinological (eg, GH treatment) support may be beneficial; Prophylaxis against specific infectious agents is indicated; Certain types of medications, such as sympathomimetic or nephrotoxic agents should be avoided or used judiciously if necessary 13764315; 4688793; 2702087; 7554350; 11919560; 12506140; 12728091; 15108277; 15706593; 16523049; 21896375; 20301501; 21046169; 22464505; 22882926; 23041322; 23941846; 24114580; 24162162 PKLR 9020 5313 Pyruvate kinase deficiency of red cells AR Pediatric Allelic with Adenosine triphosphate, elevated, of erythrocytes (AD) Hematologic Hematologic In some individuals, due to severe anemia, RBC transfusion and/or splenectomy may be beneficial 13924348; 13919474; 14014643; 14255553; 14300761; 4160306; 5940199; 7426754; 1896471; 1536957; 8285758; 7949104; 7706479; 8161798; 8807089; 8664896; 8579052; 8616073; 9090535; 9057665; 9160692; 9657767; 9886305; 10772876; 9827908; 12393511; 15491302; 15953013; 15982340; 16704447; 18420493; 18759866; 19085939; 19743919; 23082140 PKP1 9023 5317 Ectodermal dysplasia/skin fragility syndrome AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9326952; 10951270; 1615972; 19016709; 22309335 PKP2 9024 5318 Arrhythmogenic right ventricular dysplasia, familial 9 AD Pediatric Cardiovascular Cardiovascular Due to risk of severe sequelae including sudden cardiac death, individuals require ICD placement regardless of classic risk factors related to ICD necessity in clinically similar patients without PKP2 variants 15489853; 16549640; 20301310 PLA2G4A 9035 5321 Gastrointestinal ulceration, recurrent, with dysfunctional platelets AR Pediatric Gastrointestinal; Hematologic Gastrointestinal; Hematologic Surveillance for bleeding complications may be beneficial, as a described individual had chronic GI blood loss from childhood, with multiple small intestinal ulcers discovered in the context of severe bleeding and perforations during adulthood; Awareness of GI complications, including Cryptogenic multifocal ulcerating stenosing enteritis, as has been described in one pair of siblings, may allow early medical and/or surgical management 18451993; 23268370 PLA2G5 9038 5322 Fleck retina, familial benign AR N/A N/A Ophthalmologic General The clinical relevance of the condition is unclear 8703867; 17502520; 22137173 PLA2G6 9039 8398 Parkinson disease 14, autosomal recessive AR Adult Allelic with Neurodegeneration with brain iron accumulation 2A (AR); Neurodegeneration with brain iron accumulation 2B (AR) Neurologic Neurologic Some individuals with Neurodegeneration with brain iron accumulation have been described as having Karak syndrome In Parkinson disease 14, response to levodopa has been documented 17033970; 16783378; 18443314; 18981035; 18570303; 20584031; 20886109; 20938027; 21520282; 21700586; 21812034; 22934738 PLA2G7 9040 7941 Platelet-activating factor acetylhydrolase deficiency AR N/A N/A Biochemical; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3198761; 8675689; 10194471; 10733466 PLAA 9043 9373 Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28007986; 28413018 PLAG1 9045 5324 Silver-Russell syndrome 4 AD Pediatric Craniofacial; Endocrine; Musculoskeletal Endocrine Among other findings, response to growth hormone therapy has been described, and awareness may allow early diagnosis and management of this issue 28796236 PLAGL1 9046 5325 Diabetes mellitus, transient neonatal AD Pediatric Endocrine Endocrine The pathogenesis may involve loss of methylation Individuals present early in life with failure to thrive, hyperglycemia, and dehydration, and prompt recognition and treatment can reduce morbidity 11448939; 20803656 PLAU 9052 5328 Quebec platelet disorder AD Pediatric Hematologic Hematologic Fibrinolytic inhibitors can be effective for treatment of bleeding disorder 15026313; 18988861; 20007542 PLCB1 15917 23236 Developmental and epileptic encephalopathy 12 AR Pediatric Neurologic Neurologic As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Individuals may manifest with seizures, and specific knowledge of the underlying cause can help direct selection of optimal therapies for management based on the genetic etiology 20833646; 22690784; 28331464 PLCB3 9056 5331 Spondylometaphyseal dysplasia with corneal dystrophy AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29122926 PLCB4 9059 5332 Auriculocondylar syndrome 2 AD N/A N/A Craniofacial General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16114046; 22560091 PLCD1 9060 5333 Nail disorder, nonsyndromic congenital, 3 AD/AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21665001 PLCE1 17175 51196 Nephrotic syndrome, type 3 AR N/A N/A Renal General Most described individuals have had steroid-resistant disease Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17086182; 18065803; 20591883; 21415313; 23349334; 23595123 PLCG2 9066 5336 Familial cold autoinflammatory syndrome 3 (PLAID); Autoinflammation, antibody deficiency, and immune dysregulation syndrome (APLAID) AD Pediatric Allergy/Immunology/Infectious; Dermatologic Allergy/Immunology/Infectious Individuals with Familial cold autoinflammatory syndrome 3 (PLAID) may be susceptible to recurrent and severe infections, and prophylaxis (eg, with IVIG) as well as early and aggressive treatment of infections may be beneficial; Individuals with APLAID may present with multi-system inflammation (eg, affecting the skin and GI system), and may demonstrate immune deficiency (eg, with frequent upper respiratory infections), and medical treatment (eg, with IL1 antagonists and high-dose corticosteroids) has been reported as beneficial 19910034; 22236196; 23000145 PLCZ1 19218 89869 Spermatogenic failure 17 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26721930 PLD1 9067 5337 Cardiac valvular defect, developmental AR Pediatric Cardiovascular Cardiovascular Individuals may manifest with cardiac valvular disease, and awareness may allow early diagnosis and medical or surgical management 27799408 PLD3 17158 23646 Spinocerebellar ataxia 46 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8595484; 29053796 PLEC 9069 5339 Muscular dystrophy, limb-girdle, type 2Q; Epidermolysis bullosa simplex with pyloric atresia; Epidermolysis bullosa simplex with muscular dystrophy; Epidermolysis bullosa simplex, Ogna type; Epidermolysis bullosa simplex with nail dystrophy AR N/A N/A Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7136614; 3355199; 2662909; 8894687; 8696340; 10446808; 10570379; 11122061; 11851880; 14675180; 15681471; 15654962; 21109228; 21263134; 21674528; 25712130 PLEKHG2 29515 64857 Leukodystrophy and acquired microcephaly with or without dystonia AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26573021 PLEKHG5 29105 57449 Charcot-Marie-Tooth disease, recessive intermediate C; Spinal muscular atrophy, distal, autosomal recessive, 4 AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16728649; 17564964; 23777631; 23844677 PLEKHM1 29017 9842 Osteopetrosis, autosomal dominant 3; Osteopetrosis, autosomal recessive 6 AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17404618; 17997709; 27291868 PLG 9071 5340 Plasminogen deficiency, type I AR Pediatric Dermatologic; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic; Pulmonary Hematologic; Ophthalmologic Medical treatment (eg, with hyaluronidase-containing eyedrops, topical corticosteroids, heparin, FFP, immunosuppression, and lysine-conjugated plasminogen) has been described as variably beneficial 3723296; 9242524; 9834305; 10233898; 16849641; 17900274; 21174000 PLIN1 9076 5346 Lipodystrophy, familial partial, type 4 AD Pediatric Cardiovascular; Endocrine; Gastrointestinal Cardiovascular; Endocrine; Gastrointestinal Medical treatment of factors such as diabetes, hypertension, and lipid abnormalities may be beneficial to reduce morbidity/mortality; Recognition and treatment of hypertriglyceridemia can help avoid sequelae such as acute pancreatitis 21345103; 21757733 PLK4 11397 10733 Microcephaly and chorioretinopathy, autosomal recessive 2 AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25320347; 25344692 PLN 9080 5350 Cardiomyopathy, dilated, 1P; Cardiomyopathy, familial hypertrophic, 18 AD/AR Pediatric Cardiovascular Cardiovascular The severity may depend on inheritance (ie, heterozygosity vs. homozygosity/compound heterozygosity) Surveillance and preventive measures, including medical management, may reduce morbidity and mortality 12639993; 12705874; 12610310; 16432188; 17655857; 18241046; 21167350 PLOD1 9081 5351 Ehlers-Danlos syndrome, kyphoscoliotic type, 1 AR Pediatric Cardiovascular; Dermatologic; Musculoskeletal; Ophthalmologic; Renal Cardiovascular; Ophthalmologic; Renal EDS VI may be clinically recognizable, but care may be considered related to issues such as potential severe vascular rupture (beneficial preventive measures include blood pressure management); Adequate hydration to prevent nephroliathisis may be beneficial; Though not frequent, individuals may demonstrate ophthalmologic sequelae (eg, glaucoma), and appropriate surveillance and preventive measures may be beneficial 4342967; 5027136; 5016372; 4373475; 1184396; 429005; 2504907; 8449506; 7977351; 8574422; 9152832; 9220536; 9557891; 9686670; 15666309; 15979919; 16329110; 17100196; 19320026; 20301635; 22001912 PLOD2 9082 5352 Bruck syndrome 2 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12881513; 15523624; 22689593 PLOD3 9083 8985 Bone fragility with contractures, arterial rupture, and deafness AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Musculoskeletal; Ophthalmologic Audiologic/Otolaryngologic; Cardiovascular The condition may be clinically recognizable in most individuals, but recognition may allow surveillance for and prompt treatment of vascular anomalies; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 18834968 PLP1 9086 5354 Spastic paraplegia-2; Pelizaeus-Merzbacher disease XL N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2479017; 2773936; 7539211; 8659540; 8696336; 10210128; 10417279; 11093273; 11761472; 15627202; 16130097; 16157902; 16374829; 16778599; 17438221; 17568416; 18190592; 19396823; 20513814; 20660364; 21623770; 22422208; 27882623; 29478609; 29486744 PLPBP 9457 11212 Epilepsy, early-onset, vitamin B6-dependent AR Pediatric Neurologic Neurologic The condition involves neonatal or early-onset seizures, and medical treatment (with activated vitamin B6 and/or pyridoxine) has been reported as beneficial related to seizure control 27912044 PLS1 9090 5357 Deafness, autosomal dominant 76 AD Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 30872814; 31397523 PLS3 9091 5358 Osteoporosis and osteoporotic fractures XL N/A N/A Musculoskeletal General Variants may also act as susceptibility factors related to osteoporosis, fractures, and related phenotypes Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24088043 PLVAP 13635 83483 Diarrhea 10, protein-losing enteropathy type AR Pediatric Craniofacial; Gastrointestinal; Genitourinary Gastrointestinal The condition can involve severe protein-losing enteropathy, and awareness may allow early diagnosis and management (eg, with low-fat diet and middle-chain triglyceride-rich formula) which has been reported as beneficial in some individuals 26207260; 29661969; 29875123 PMFBP1 17728 83449 Spermatogenic failure 31 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30032984 PMM2 9115 5373 Congenital disorder of glycosylation, type Ia AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 6543331; 3703266; 2890978; 3162953; 2466439; 1929507; 1293380; 8256592; 9140401; 10571009; 10527672; 10801058; 11916319; 11134235; 11343337; 11596651; 12905014; 17158594; 18203160; 20301507; 20301289; 21937992 PMP2 9117 5375 Charcot-Marie-Tooth disease, demyelinating, type 1G AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26257172; 26828946; 27009151; 30249361 PMP22 9118 5376 Roussy-Levy syndrome; Charcot-Marie-Tooth syndrome, type 1A; Charcot-Marie-Tooth syndrome with deafness (type 1E); Neuropathy, hereditary, with liability to pressurve palsies; Dejerine-Sottas disease; Neuropathy, inflammatory demyelinating AD/AR N/A N/A Audiologic/Otolaryngologic; Neurologic General CMT, 1A can be due to a common 17p11.2 duplication; The variant type (eg, deletions vs. duplications) influences the phenotype; Compound heterozygous variants have been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13184660; 7139106; 2290479; 1349106; 1303281; 8422677; 7834893; 7903071; 8012388; 8210227; 7501152; 7666403; 8644705; 8981968; 9208274; 9179161; 9391880; 9543325; 9703447; 10489052; 10330345; 10211478; 11376203; 11835375; 12439896; 12499508; 12427913; 12084875; 12578939; 15205993; 17620487; 18698610; 19705173; 19888301; 20301566; 20301384; 22006697; 22190321; 22382358 PMPCA 18667 23203 Spinocerebellar ataxia, autosomal recessive 2 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10528257; 25808372; 26657514 PMPCB 9119 9512 Multiple mitochondrial dysfunctions syndrome 6 AR N/A N/A Biochemical General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29576218 PMS2 9122 5395 Colorectal cancer, hereditary nonpolyposis type 4; Mismatch repair cancer syndrome 4 AD/AR Adult (Colorectal cancer, hereditary nonpolyposis type 4)/Pediatric (Mismatch repair cancer syndrome) Dermatologic; Oncologic Oncologic Individuals may be at risk for additional types of malignancy For surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types (individuals may be at risk of a number of cancer types), awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; Individuals with Mismatch repair cancer syndrome are at risk of multiple types of malignancy, and awareness may allow early detection and management 8072530; 7661930; 4574005; 15077197; 17557300; 19851131; 20587412; 20301390; 22461402; 22577899; 22933731; 24434690; 25856668; 29345684 PMVK 9141 10654 Porokeratosis 1, multiple types AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26202976 PNKP 9154 11284 Ataxia-oculomotor apraxia 4; Charcot-Marie-Tooth disease, type 2B2; Microcephaly, seizures, and developmental delay AR N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20118933; 23224214; 25728773; 27066567; 30039206 PNLIP 9155 5406 Pancreatic lipase deficiency AR Pediatric Gastrointestinal Gastrointestinal Individuals have been described with exocrine pancreatic failure, and medical management (eg, with ADEK vitamin and pancreatic enzyme replacement) has been described as beneficial 24262094 PNP 7892 4860 Purine nucleoside phosphorylase deficiency AR Pediatric Allergy/Immunology/Infectious; Biochemical; Neurologic; Oncologic Allergy/Immunology/Infectious ; Oncologic Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Surveillance for malignancy (eg, lymphoma has been described) can be beneficial; BMT/HSCT has been reported 5579411; 825775; 102751; 111549; 6774252; 3029074; 1931007; 1384322; 8774508; 8931706; 9067751; 9737781; 11498751; 11453975; 11902746; 17910661; 18208442; 19584574; 19733163; 19657670; 20544539; 22132981 PNPLA1 21246 285848 Ichthyosis, congenital, autosomal recessive 10 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22246504; 24344921; 26691440; 28403545 PNPLA2 30802 57104 Neutral lipid storage disease with myopathy AR N/A N/A Dermatologic; Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17187067; 22832386 PNPLA6 16268 10908 Boucher-Neuhauser syndrome; Laurence-Moon syndrome; Oliver-McFarlane syndrome AR Pediatric Allelic with Spastic paraplegia 39 (AR) Craniofacial; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic Endocrine For Boucher-Neuhauser syndrome, Laurence-Moon syndrome, and Oliver-McFarlane syndrome, management related to hypogonadotropic hyponadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) may be beneficial; Related to fertility in Boucher-Neuhaser syndrome, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required; For Oliver-McFarlane syndrome, recognition of other pituitary deficiencies (such as thyroid hormone deficiency) may allow prompt diagnosis and medical management 8053762; 18313024; 24355708; 25033069; 25480986 PNPLA8 28900 50640 Mitochondrial myopathy with lactic acidosis AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25512002 PNPO 30260 55163 Pyridoxamine 5'-phosphate oxidase deficiency AR Pediatric Biochemical; Neurologic Biochemical; Neurologic Individuals may manifest with severe seizures starting in the immediate neonatal period (or even before birth), and medical treatment (with pyridoxal phosphate) can be effective as an antiepileptic agent 12200739; 12747882; 15772097; 24266778; 24658933; 28331464 PNPT1 23166 87178 Deafness, autosomal recessive 70 AR Pediatric Allelic with Combined oxidative phosphorylation deficiency 13 (AR) Audiologic/Otolaryngologic; Biochemical; Neurologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 23084290; 23084291 POC1A 24488 25886 Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis (SOFT syndrome) AR N/A N/A Craniofacial; Dental; Dermatologic; Endocrine; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22840363; 22840364; 22440536 POC1B 30836 282809 Cone-rod dystrophy 20 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24945461; 25018096 POF1B 13711 79983 Premature ovarian failure 2B XL Pediatric Endocrine; Obstetric Obstetric Genetic knowledge may allow fertility preservation such as by storing eggs 16773570 POFUT1 14988 23509 Dowling-Degos disease 2 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23684010 POGLUT1 22954 56983 Dowling-Degos disease 4; Muscular dystrophy, limb-girdle, autosomal recessive 21 AD/AR N/A N/A Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21971768; 24387993; 27807076 POGZ 18801 23126 Mental retardation, autosomal dominant 37 (White-Sutton syndrome) AD N/A N/A Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25533962; 26739615 POLA1 9173 5422 Pigmentary disorder, reticulate, with systemic manifestations, X-linked; Van Esch-O'Driscoll syndrome XL Pediatric Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic Allergy/Immunology/Infectious Males have been described with manifestations including recurrent respiratory infections and failure to thrive due to inflammatory gastroenteritis or colitis, and awareness, and awareness may allow preventative measures and early and aggressive treatments of infections 16053905; 27019227; 31006512 POLD1 9175 5424 Colorectal cancer, susceptibility to, 10 AD Pediatric Allelic with Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (AD) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Endocrine; Musculoskeletal; Oncologic Allergy/Immunology/Infectious; Oncologic Individuals have been described such that the presence of variants would warrant surveillance in the pediatric period Described individuals manifest with colorectal adenomas, with a high risk of colorectal carcinoma, and screening (eg, with colonoscopy) may allow early detection and treatment, potentially ameliorating morbidity and mortality; Other neoplasms (eg, an increased risk of endometrial cancer has been reported) have been described in affected individuals, and knowledge of the increased risk may allow early detection and treatment 20631028; 23263490; 23770608; 24501277 POLE 9177 5426 Colorectal cancer, susceptibility to, 12; Facial dysmorphism, immunodeficiency, livedo, and short stature syndrome (FILS syndrome); Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency (IMAGEI) AD/AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Oncologic Allergy/Immunology/Infectious; Endocrine; Oncologic In Colorectal cancer, susceptibility to, individuals have been described such that the presence of variants would warrant surveillance in the pediatric period In Colorectal cancer, susceptibility to, described individuals manifest edwith colorectal adenomas, with a high risk of colorectal carcinoma, and screening (eg, with colonoscopy) may allow early detection and treatment, potentially ameliorating morbidity and mortality; Other neoplasms have been described in affected individuals, and knowledge of the increased risk may allow early detection and treatment; In FILS syndrome and IMAGEI, individuals may have immunodeficiency, and prophylactic measures and awareness of the risk of infections may allow early and aggressive treatment of infectious manifestations; In IMAGEI, the condition may include adrenal insufficiency, and awareness may allow medical management of the condition 14760276; 16835919; 23230001; 23263490; 24501277; 25370038; 30503519 POLG 9179 5428 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1; Mitochondrial DNA depletion syndrome 4B; Sensory ataxia, dysarthria, and ophthalmoparesis; Mitochondrial DNA depletion syndrome 4A (Alpers type); Alpers syndrome; POLG-related ataxia neuropathy spectrum disorders AD/AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic General Conditions can include cardiomyopathy; Hepatotoxic medications should be avoided Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14851183; 14467368; 2725645; 13971413; 6033104; 4647849; 1252162; 2246481; 2067633; 8368248; 7897414; 9894877; 11431686; 11571332; 12210792; 12297582; 12825077; 15351195; 15534189; 15122711; 15477547; 15929042; 15689359; 16177225; 16130100; 16634032; 17502560; 6957900; 18487244; 18195149; 19307547; 19752458; 20301791; 20558295; 20837861; 20837862; 20142534; 20220442; 21357833; 21670405 POLG2 9180 11232 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4; Mitochondrial DNA depletion syndrome 16 AD/AR N/A N/A Biochemical; Gastrointestinal; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12975295; 15351195; 16685652; 20405137; 22155748; 27592148; 30157269 POLH 9181 5429 Xeroderma pigmentosum, variant type AR Pediatric Dermatologic; Oncologic Dermatologic; Oncologic Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance for dermatologic manifestations can be beneficial 10398605; 10385124; 20301571; 23630442; 23651273; 23755135 POLR1A 17264 25885 Acrofacial dysostosis, Cincinnati type AD N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25913037 POLR1B 20454 84172 Treacher-Collins syndrome 4 AD Pediatric Audiologic/Otolaryngologic; Craniofacial Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 31649276 POLR1C 20194 9533 Treacher Collins syndrome 3 AR Pediatric Allelic with Leukodystrophy, hypomyelinating, 11 (AR) Audiologic/Otolaryngologic; Craniofacial; Dental; Neurologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 21131976; 26151409 POLR1D 20422 51082 Treacher Collins syndrome 2 AD/AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Dental Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 21131976; 24603435; 25790162 POLR3A 30074 11128 Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism; Wiedemann-Rautenstrauch syndrome AR N/A N/A Craniofacial; Dental; Endocrine; Musculoskeletal; Neurologic; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12605447; 17159124; 20640464; 21855841; 25339210; 27612211; 30323018; 30414627; 30450527 POLR3B 30348 55703 Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism AR N/A N/A Dental; Endocrine; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22036171; 22036172; 25339210 POLR3GL 28466 84265 Short stature, oligodontia, dysmorphic facies, and motor delay AR Pediatric Cardiovascular; Craniofacial; Dental; Musculoskeletal; Neurologic General Among other findings, the condition may include potentially occult cardiovascular anomalies, and awareness may enable surveillance, early diagnosis, and management 31089205; 31695177 POLR3K 14121 51728 Leukodystrophy, hypomyelinating 21 AR N/A N/A Gastrointestinal; Genitourinary; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30584594 POMC 9201 5443 Obesity, early onset, with adrenal insufficiency and red hair AR Pediatric Dermatologic; Endocrine Endocrine The condition can present with adrenal insufficiency, and medical treatment (eg, with glucocorticoid replacement therapy) can be beneficial , though may not affect certain manifestations such as obesity 9620771; 14557433; 18765507; 22570972; 23293326 POMGNT1 19139 55624 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 3; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3; Retinitis pigmentosa 76 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11709191; 12588800; 15236414; 17030669; 17878207; 19067344; 19299310; 26908613; 27391550 POMGNT2 25902 84892 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8 AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22958903; 27066570 POMK 26267 84197 Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A, 12; Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type C, 12; Muscle-eye brain disease; Walker-Warburg syndrome AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23519211; 24556084; 24925318 POMP 20330 51371 Proteasome-associated autoinflammatory syndrome 2 AD Pediatric Allelic with Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (AR) Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Musculoskeletal Allergy/Immunology/Infectious Individuals have been described with recurrent infections, and awareness may allow preventative measures and early and aggressive treatment of infections; HSCT has been described 12022327; 20226437; 26524591; 29805043 POMT1 9202 10585 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 AR Pediatric Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular Conditions may involve cardiovascular manifestations (including dilated cardiomyopathy) and surveillance (eg, with echocardiography) may allow early medical management 2494887; 11053679; 11320179; 12369018; 14678799; 15037715; 15792865; 15637732; 16717220; 16575835; 17878207; 19299310; 20065251; 22727687 POMT2 19743 29954 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 ; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C 2 AR Pediatric Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular Conditions may involve cardiovascular manifestations (including dilated cardiomyopathy) and surveillance (eg, with echocardiography) may allow early medical management 15894594; 16701995; 17923109; 17878207; 19067344; 19299310; 19138766; 20301468; 20816175; 22727687 PON1 9204 5444 Clopidogrel treatment, sensitivity to AD/AR Pediatric General Pharmacogenomic Among other associations, variants may be associated with susceptibility to stent thrombosis, possibly related to clopidogrel metabolism, and may thus have pharmacogenomic importance 8896566; 11888590; 12454802; 21170047 POP1 30129 10940 Anauxetic dysplasia 2 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21455487; 27380734; 28067412 POPDC3 17649 64208 Muscular dystrophy, limb-girdle, autosomal recessive 26 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31610034 POR 9208 5447 Antley-Bixler syndrome; Disordered steroidogenesis due to cytochrome p450 oxidoreductase deficiency AR Pediatric Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic Endocrine Hydrocortisone replacement therapy can be effective for cortisol deficiency, including administation of stress-dose steroids; In males, testosterone therapy can help with undervirilization in puberty 2932643; 0633130; 12116245; 11742006; 12917333; 15220035; 14758361; 14513299; 15793702; 16906539; 18559916; 19837910; 19884324; 20124576; 20410220; 20818252; 20844025; 21070833; 22162478 PORCN 17652 64840 Focal dermal hypoplasia XL N/A N/A Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13948891; 1190805; 843447; 17546031; 17546030; 18325042; 19309688; 19863546; 19586929; 20420028; 21332693; 21472892; 21484999; 21732017; 22414489; 22250236; 22735390; 23131169; 23399492 POT1 17284 25913 Glioma susceptibility 9; Melanoma, cutaneous malignant, susceptibility to 10 AD Pediatric Oncologic Oncologic Susceptibility to cancer types other than melanoma and glioma has been suggested in the reported families Awareness of risk of glioma and melanoma (as well as other malignancies) may allow surveillance and early disease detection and management 24686846; 24686849; 25482530 POU1F1 9210 5449 Pituitary hormone deficiency, combined 1 AR Pediatric Cardiovascular; Endocrine Cardiovascular; Endocrine A minority of individuals have been described with cardiac anomalies Individuals may manifest with central deficiency of multiple hormones, which can result in severe sequelae if untreated, and replacement therapy can be effective 2634610; 1302000; 15928241; 16060904; 18059085; 19498317; 21316014; 21521297; 21722153; 22010633 POU3F3 9216 5455 Snijders Block-Fisher syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31303265 POU3F4 9217 5456 Deafness, X-linked 2 XL Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; It has been suggested that that stapes surgery should not be performed due to a high likelihood of complications (the use of cochlear implants has been reported as beneficial) 5173351; 6662621; 1922747; 7839145; 7581392; 19438930; 19671658; 19930154; 20412083; 21193157; 21250553; 21555964; 23076972; 23606368 POU4F3 9220 5459 Deafness, autosomal dominant 15 AD N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9506947; 18228599; 18347256; 19372648; 19462854; 20434433; 22938506 POU6F2 21694 11281 Wilms tumor 5 AD Pediatric Oncologic Oncologic Germline variants can predispose to disease due to loss of heterozygosity Individuals may be at high risk for Wilms tumor, and surveillance may allow early diagnosis and treatment 11284034 PPA2 28883 27068 Sudden cardiac failure, alcohol induced AR Pediatric Allelic with Sudden cardiac failure, infantile (AR) Cardiovascular; Musculoskeletal; Neurologic General Individuals have been reported as suffering sudden cardiac failure after ingesting small amounts of alcohol, and awareness may allow avoidance of triggering agents as well as early diagnosis allowing preventive measures (eg, ICD) 27523597; 27523598 PPARG 9236 5468 Lipodystrophy, familial, partial, type 3; Insulin resistance, severe, digenic AD/Digenic (Severe digenic insulin resistance can be due to digenic variants in PPP1R3A and PPARG) N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9425261; 9753710; 10622252; 10973253; 11788685; 12453919; 12118251; 15356014; 21079616; 21479595; 21865368; 22748602; 22803842 PPCS 25686 79717 Cardiomyopathy, dilated, 2C AR Pediatric Cardiovascular Cardiovascular Individuals have been described as affected by dilated cardiomyopathy, and awareness may allow prompt management (eg, oral pantethine supplementation has been described as beneficial) 29754768 PPIB 9255 5479 Osteogenesis imperfecta, type IX AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19781681; 20089953; 22718341; 23613367 PPIP5K2 29035 23262 Deafness, autosomal recessive 100 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 29590114 PPM1D 9277 8493 Intellectual developmental disorder with gastrointestinal difficulties and high pain threhold (Jansen-De Vries syndrome) AD N/A N/A Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28343630 PPM1K 25415 152926 Maple syrup urine disease, mild variant AR Pediatric Biochemical Biochemical The condition can result in neurologic sequelae, and medical/dietary treatment (with low protein diet without branched-chain amino acids) can allow normal cognitive development 23086801 PPOX 9280 5498 Porphyria variegata AD/AR Pediatric Biochemical; Dermatologic; Musculoskeletal; Neurologic; Renal Dermatologic; Pharmacogenomic Homozygosity/compound heterozygosity results in a distinct and much more severe phenotype Acute attacks may be precipitated by porphyrinogenic agents, which, along with other exacerbating factors, should be avoided; Skin protection is warranted 6143163; 4059081; 3723537; 3319294; 2222353; 2020301; 8852667; 8673113; 8817334; 9738863; 9811936; 10401000; 11286631; 12357337; 19460837; 19656457; 19845869; 21734717; 21910705 PPP1CB 9282 5500 Noonan syndrome-like disorder with loose anagen hair 2 AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic Cardiovascular Surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis and valvular anomalies) can be beneficial 25356899; 27264673; 27681385; 27868344; 28211982 PPP1R12A 7618 4659 Genitourinary and/or/brain malformation syndrome AD N/A N/A Genitourinary; Gastrointestinal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31883643 PPP1R15B 14951 84919 Microcephaly, short stature, and impaired glucose metabolism 2 AR Pediatric Craniofacial; Endocrine; Musculoskeletal; Neurologic Endocrine Awareness of the risk of diabetes may allow prompt recognition and treatment 26159176; 26307080 PPP1R3A 9291 5506 Insulin resistance, severe, digenic Digenic N/A N/A Endocrine General Severe digenic insulin resistance has been reported as resulting from digenic variants in PPP1R3A and PPARG Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12118251 PPP2CA 9299 5515 Neurodevelopmental disorder and language delay with or without structural brain abnormalities AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30595372 PPP2R1A 9302 5518 Mental retardation, autosomal dominant 36 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25533962; 26168268 PPP2R2B 9305 5521 Spinocerebellar ataxia 12 AD N/A N/A Neurologic General The condition involves expansion of triplet repeats Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10581021; 11719278; 14526180; 16138911; 20301381; 20629122 PPP2R3C 17485 55012 Spermatogenic failure 36; Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy AD/AR N/A N/A Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30893644 PPP2R5D 9312 5528 Mental retardation, autosomal dominant 35 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25533962; 25972378; 26168268 PPP3CA 9314 5530 Developmental and epileptic encephalopathy 91; Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28942967; 29432562 PPT1 9325 5538 Ceroid lipofuscinosis, neuronal, 1 AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5706364; 4121459; 4698309; 6890163; 7637805; 9664077; 9425237; 9535296; 11506414; 15965709; 17261688; 21235444; 21990111 PQBP1 9330 10084 Renpenning syndrome 1 XL N/A N/A Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13981686; 3177467; 7943045; 9599645; 11950858; 14634649; 15024694; 15811016; 15782410; 16493439; 16740914; 17033686; 20886605; 20950397; 21204222; 21267006; 21315190; 22710169 PRCD 32528 768206 Retinitis pigmentosa 36 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16938425 PRDM12 13997 59335 Neuropathy, hereditary sensory and autonomic, type VIII AR N/A N/A Neurologic General Insensitivity to pain can result in injuries and infections Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26005867 PRDM13 13998 59336 Chorioretinal atrophy, progressive bifocal AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5686965; 30710461 PRDM16 14000 63976 Cardiomyopathy, dilated, ILL; Left ventricular noncompaction 8 AD Pediatric Cardiovascular Cardiovascular Individuals have been described as manifesting with findings such as arrhythmias, cardiac valvular abnormalities, and dilated cardiomyopathy, and surveillance (eg, with echocardiogram and electrocardiogram) may allow early medical and/or surgical interventions (eg, intracardiac defibrillator) may be beneficial in terms of reducing disease-associated morbidity and mortality 18506004; 21551322; 23768516 PRDM5 9349 11107 Brittle cornea syndrome 2 AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic Ophthalmologic Manifestations can occur in heterozygote Individuals are prone to ophthalmologic injury (such as corneal rupture) with minimal trauma, and protective measures may be beneficial 21664999; 22122778; 26395458 PRDM6 9350 93166 Patent ductus arteriosus 3 AD N/A N/A Cardiovascular General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4284236; 27181681 PRDM8 13993 56978 Epilepsy, progressive myoclonic, 10 AR N/A N/A Neurologic General As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22961547 PRDX1 9352 5052 Methylmalonic aciduria and homocystinuria, cblC type, digenic AR/Digenic Pediatric Biochemical; Cardiovascular; Dermatologic; Hematologic; Neurologic; Ophthalmologic; Renal Biochemical Compound heterozygosity and digenic inheritance (with MMACHC) has been described While no treatment is completely effective, specific dietary (eg, high-calorie, low protein diet and avoidance of fasting, with measures taken to avoid/treat decompensation) and other medical measures (eg, cofactor therapy) may be beneficial to treat and prevent sequelae in the acute and chronic states 29302025 PREPL 30228 9581 Myasthenic syndrome, congenital 22 AR Pediatric Neurologic Neurologic Medical treatment with acetylcholine esterase inhibitors has been described as beneficial in one individual; In infancy, the use of apnea monitors may be indicated; Agents that affect neuromuscular transmission and exacerbate myasthenic manifestations should be avoided 24610330 PRF1 9360 5551 Hemophagocytic lymphohistiocytosis, familial, 2; Lymphoma, non-Hodgkin; Aplastic anemia, adult-onset AR Pediatric Allergy/Immunology/Infectious; Hematologic; Oncologic Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals with Aplastic anemia, adult-onset may have manifestations after the pediatric period In Lymphoma, non-Hodgkin; Aplastic anemia, adult-onset, surveillance and early treatment of hematologic (eg, anemia, bone marrow failure) and malignant complications may reduce morbidity; In Hemophagocytic lymphohistiocytosis, familial, 2 (as well as Immune-mediated neurodegeneration, infection triggered, at least theoretically), antibiotics or antiviral agents can be beneficial to treat/prevent infections that can trigger an exaggerated inflammatory response; Chemo/immunotherapy can achieve clinical stability prior to allogeneic HSCT, which can be effective 10583959; 12229880; 12358924; 14757862; 15659737; 17311987; 15728124; 17873118; 21936944; 21959744; 22029169; 22186995; 22359105; 23443029 PRG4 9364 10216 Camptodactyly-arthropathy-coxa vara-pericarditis syndrome AR Pediatric Cardiovascular; Musculoskeletal Cardiovascular The disorder may be recognizable by noncardiac manifestations, but individuals frequently develop pericarditis refractory to other treatments and requiring pericardiectomy, and awareness may allow early detection and efficient targeted medical management 940709; 656159; 6866038; 6870971; 4083939; 3964320; 3964321; 8835575; 9550484; 10545950; 11102929; 16429407; 21565623 PRICKLE1 17019 144165 Epilepsy, progressive myoclonic, 1B AD/AR N/A N/A Neurologic General As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15634728; 15642921; 16376507; 18976727; 21276947 PRICKLE2 20340 166336 Epilepsy, progessive myoclonic 5 AD N/A N/A Neurologic General As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 632821; 21276947 PRIMPOL 26575 201973 Myopia 22, autosomal dominant AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23579484 PRKACA 9380 5566 Primary pigmented nodular adrenocortical disease 4;Cardioacrofacial dysplasia 1 AD Pediatric Cardiovascular; Craniofacial; Dental; Endocrine; Musculoskeletal Cardiovascular; Endocrine Mosaicism has been described in Cardioacrofacial dysplasia 1 In Primary pigmented nodular adrenocortical disease 4, awareness may allow early management of adrenal disease (eg, potentially including surgical intervention), which may be beneficial; Cardioacrofacial dysplasia 1 may include congenital cardiovascular anomalies (among other features), and awareness may allow prompt recognition and management of these issues 24571724; 24700472; 24747643; 33058759 PRKACB 9381 5567 Cardioacrofacial dysplasia 2 AD Pediatric Cardiovascular; Craniofacial; Dental; Musculoskeletal; Neurologic Cardiovascular Mosaicism has been described in Cardioacrofacial dysplasia 2 Cardioacrofacial dysplasia 2 may include congenital cardiovascular anomalies (among other features), and awareness may allow prompt recognition and management of these issues 33058759 PRKACG 9382 5568 Bleeding disorder, platelet-type, 19 AR Pediatric Hematologic Hematologic Individuals have been described as manifesting with spontaneous bleeding episodes in childhood, and awareness may allow preventive measures and early management of bleeding diatheses 25061177 PRKAG2 9386 51422 Cardiomyopathy, familial hypertrophic 6; Wolff-Parkinson-White syndrome AD Pediatric Allelic with Glycogen storage disease of heart, lethal congenital (AD) Cardiovascular; Craniofacial; Musculoskeletal; Renal Cardiovascular Surveillance measures (eg, including echocardiography and electrocardiography) and medical and preventive management related to cardiac hypertrophy, as well as arrhythmia, may ameliorate/prevent severe sequelae 13619017; 15371577; 10820940; 11371514; 11586962; 11827995; 15673802; 15877279; 16716659; 16487706; 18403758; 19787389 PRKAG3 9387 53632 Increased glyogen content in skeletal muscle AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17878938 PRKAR1A 9388 5573 Pigmented nodular adrenocortical disease, primary, 1; Carney complex, type 1; Myxoma, intracardiac; Acrodysostosis 1, with or without hormone resistance AD Pediatric Cardiovascular; Dermatologic; Endocrine; Musculoskeletal; Neurologic; Oncologic Endocrine; Oncologic Surveillance for neoplasms (eg, cardiac myxomas), as well as multiple endocrine-related manifestations can allow early detection and treatment, which can involve surgical excision of the neoplasm; Additional surveillance for endocrine abnormalities can allow early interventions 1263542; 579530; 6329005; 4010501; 3465316; 3365080; 2605794; 2586567; 1571257; 9415461; 9215269; 9805140; 10523219; 10974026; 10973256; 11549623; 12213893; 20507346; 21651393; 22464252; 22464250; 20301463 PRKCD 9399 5580 Autoimmune lymphoproliferative syndrome type III AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; medical management (eg, with immunosuppressive agents) of autoimmune manifestations has been described as beneficial 23319571; 23430113; 23666743 PRKCG 9402 5582 Spinocerebellar ataxia 14 AD/AR N/A N/A Neurologic General Homozygosity has been described in severe cases Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10939565; 12164726; 12644968; 14694043; 14676051; 16193476; 15841389; 19561170; 21434874; 21827914; 21937992; 22675081; 23604456 PRKCSH 9411 5589 Polycystic liver disease 1 with or without kidney cysts AD N/A N/A Gastrointestinal; Renal General Though some individuals may require treatment, it is unclear if early (genetic) diagnosis would be beneficial; Liver transplantion has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11047756; 12577059; 12529853; 16835903; 20095989; 22415584 PRKD1 9407 5587 Congenital heart defects and ectodermal dysplasia AD N/A N/A Cardiovascular; Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27479907 PRKDC 9413 5591 Immunodeficiency 26 with or without neurologic abnormalities AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Neurologic Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been reported 19075392; 23722905 PRKG1 9414 5592 Aortic aneurysm, familial thoracic 8 AD Pediatric Cardiovascular Cardiovascular Individuals have been described as suffering from sudden death secondary to aortic dissection/rupture, and surveillance and preventive measures, as well as early treatment of disease-related manifestations (including aortic aneurysms as well as other vascular anomalies), may help ameloriate morbidity and mortality 16646045; 23910461 PRKN 8607 5071 Parkinson disease 2, autosomal recessive juvenile AR Pediatric Neurologic Neurologic Individuals have been reported as responding to therapies such as levodopa 9560156; 10894217; 11487568; 11552035; 12056932; 12629236; 12891670; 12730996; 15266615; 15642918; 16130111; 16328510; 17187375; 20182943; 20837857; 20876472; 20558392 PRKRA 9438 8575 Dystonia 16 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18243799; 18420150; 20408955; 22415584; 22842711; 25142429 PRLR 9446 5618 Hyperprolactinemia; Multiple fibroadenomas of the breast AD Pediatric Multiple fibroadenomas of the breast (AD) Endocrine; Oncologic Endocrine Knowledge of variants may be additionally helpful in consideration of women with breast masses Women may require dopamine agonists after breastfeeding in order to treat galatorrhea 18779591; 24195502; 30575453 PRMT7 25557 54496 Short stature, brachydactyly, intellectual developmental disability, and seizures AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed mediCONDITIONScal decision-making, prognostic considerations, and avoidance of unnecessary testing 26437029 PRNP 9449 5621 Spongiform encephalopathy with neuropsychiatric features; Huntington disease-like 1; Gerstmann-Straussler disease; Creutzfeldt-Jakob disease; Insomnia, fatal familial; Dementia, Lewy body AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2573006; 2572450; 2564168; 2563037; 2190844; 1975028; 2159587; 1683708; 1677164; 1363809; 1439789; 1363810; 12451207; 1346338; 8595485; 9266722; 9384372; 9789072; 9792871; 10581230; 10371520; 9932941; 11593450; 11709001; 15623717; 16769939; 16831973; 17353478; 18360821; 19081515; 22097954; 22210626; 22488860; 22558438; 22561193; 22612156; 22675855; 22763467 PROC 9451 5624 Thrombophilia, hereditary, due to protein C deficiency AD/AR Pediatric Hematologic Hematologic The risks of hematologic complications may be affected by variants in other genes (eg, FVL) Individuals can demonstrate manifestations such as severe thrombophilia and high risk for a variety of cardiovascular complications, and prophylactic measures and rapid treatment of sequelae may reduce morbidity and mortality; Liver and renal transplantation have been described 6895379; 6139528; 6148564; 6547008; 6437521; 3840918; 2958610; 2437584; 3337902; 2521802; 2547423; 1944440; 8093743; 8322701; 8446940; 8049422; 7795227; 7562967; 8750805; 10942114; 11148525; 19373522; 20187890; 20727573; 22168450; 22531345 PRODH 9453 5625 Hyperprolinemia, type I AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13910064; 14497974; 4299764; 11510941; 12217952; 12525555; 17412540; 18197084; 18806117; 20524212; 23462603 PROK2 18455 60675 Hypogonadotropic hypogonadism 4 with or without anosmia AD/AR/Digenic Pediatric Craniofacial; Endocrine; Neurologic Endocrine In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 17054399; 17959774; 18285834; 20301509 PROKR2 15836 128674 Hypogonadotropic hypogonadism 3 with or without anosmia AD/AR Pediatric Craniofacial; Endocrine; Neurologic Endocrine Digenic inheritance (with KAL1) has been reported In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 17054399; 20301509 PROM1 9454 8842 Cone-rod dystrophy 12; Macular dystrophy, retinal, 2; Stargardt disease 4; Retinitis pigmentosa 41 AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10205271; 10587575; 12657606; 17605048; 18654668; 20393116; 20859302; 24474277; 26702251; 29416601; 31576780 PROP1 9455 5626 Pituitary hormone deficiency, combined, 2 AR Pediatric Endocrine Endocrine Hormone replacement therapy can be effective to treat multiple endocrinological deficiencies (eg, GH and thyroid hormone deficiency); Individuals may develop ACTH deficiency, and may require treatment including "stress dose steroids"; Medical interventions may be necessary to induce puberty 6046325; 745452; 9661653; 9768691; 9462743; 10084575; 920061; 11134108; 10634415; 11549674; 11549703; 15472175; 15531542; 20301521; 20381582; 20395664; 22024773; 22111336; 22286799 PROS1 9456 5627 Thrombophilia, hereditary, due to protein S deficiency AD/AR Pediatric Hematologic Hematologic Individuals may be at higher risk for thrombophilia, and may demonstrate thrombosis and secondary hemorrhage usually beginning in early infancy (in recessive forms); Prompt recognition may allow preventive measures and early treament, which may reduce morbidity and mortality 6239102; 6238642; 2952034; 2935209; 2231208; 2141197; 7899424; 7545463; 10442899; 10063989; 19168201; 19466456; 19826897; 20398916; 20484936; 20484936; 21172841; 21799399; 22166512 PROZ 9460 8858 Protein Z deficiency AD N/A N/A General General There is weak or mixed evidence that protein Z deficiency has an adverse health effect 7495103; 10829076; 11289354; 11895801; 15638861; 14671240; 15626740; 16938126; 20076855 PRPF3 17348 9129 Retinitis pigmentosa 18 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11773002 PRPF31 15446 26121 Retinitis pigmentosa 11 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5764686; 9345108; 11545739; 12923864; 17325180; 19506198; 19618371; 20939871; 23041261 PRPF4 17349 9128 Retinitis pigmentosa 70 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24419317 PRPF6 15860 24148 Retinitis pigmentosa 60 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21549338 PRPF8 17340 10594 Retinitis pigmentosa 13 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11468273; 20232351; 22039234 PRPH2 9942 5961 Choriodal dystrophy, central areolar 2; Retinitis punctata albescens; Macular dystrophy, vitelliform 3; Macula dystrophy, patterned 1; Retinitis pigmentosa 7 AD/Digenic N/A N/A Ophthalmologic General Digenic inheritance (with ROM1) has been reported; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13410569; 900215; 7115165; 6984500; 3718916; 1749427; 1684223; 8485575; 8251014; 8485574; 8485572; 8485576; 7519821; 8202715; 8302543; 7493155; 8689482; 8644804; 9010868; 9443872; 10532447; 14557183; 19262438; 19243827; 20213611; 22842402; 22863181; 23847139 PRPS1 9462 5631 Arts syndrome; Deafness, X-linked 1; Phosphoribosylpyrophosphate synthetase I superactivity XL Pediatric Allelic with Charcot-Marie-Tooth disease, X-linked recessive, 5 (XL); Phosphoribosylpyrophosphate synthetase I superactivity (XL); Nonsyndromic sensorineural deafness, 2, X-linked (XL) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Hematologic; Neurologic; Renal Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Renal In Arts syndrome, treatment with S-adenosylmethionine may be beneficial, and due to infectious risk, prophylaxis and early and aggressive treatment of infections may decrease related morbidity and mortality; Several PRPS1-related conditions can include deafness, which can be congenital/prelingual, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Phosphoribosylpyrophosphate synthetase I superactivity, medical treatment of uric acid overproduction can be beneficial 6069085; 5782823; 171280; 6243137; 3017368; 8498830; 8253776; 7593598; 8882866; 8968763; 10503584; 15240907; 5955956; 17701896; 17701900; 20380929; 20021999; 20301738; 22246954; 24528855; 25182139 PRRT2 30500 112476 Episodic kinesigenic dyskinesia 1 AD Pediatric Allelic with Seizures, benign familial infantile, 2 (AD); Convulsions, familial infantile, with paroxysmal choreoathetosis (AD) Neurologic Neurologic As with other disorders that manifest with seizures, maximal seizure control is beneficial In Episodic kinesigenic dyskinesia, treatment with carbamazepine has been shown to particularly effective in affected individuals 22101681; 22120146; 22243967; 22543779; 22832103; 22870186; 23535490; 28331464 PRRX1 9142 5396 Agnathia-otocephaly complex AD/AR N/A N/A Audiologic/Otolaryngologic; Craniofacial General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12244557; 21294718; 22211708; 23444262 PRSS1 9475 5644 Pancreatitis, hereditary AD Pediatric Gastrointestinal; Oncologic Gastrointestinal; Oncologic To decrease attacks, dietary measures (eg, low-fat diet), hydration, and antioxidants, with avoidance of precipitants, such as alcohol and tobacco can beneficial; Medical management (including with pancreatic enzyme replacement) may be benefiical; Individuals may be at increased risk for manifestations such as pancreatic cancer, and awareness may allow prompt detection and treatment 6023921; 8841182; 9322498; 9557894; 10204851; 18184119; 18755888; 22088471; 22094894; 22379635; 23503650; 23864476; 24236450; 24242859; 24624459 PRSS12 9477 8492 Mental retardation, autosomal recessive 1 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12459588; 12925575 PRSS56 39433 646960 Microphthalmia, isolated 6 AR Adult Ophthalmologic Ophthalmologic; Pharmacogenomic Some individuals with angle-closure glaucoma have been described, and awareness of disease risk and surveillance may allow early treatment; Agents that may contribute to glaucoma should be avoided 15823920; 19526372; 21397065; 21532570; 21850159; 23127749 PRUNE1 13420 58497 Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA) AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26539891; 28211990; 28334956 PRX 13797 57716 Dejerine-Sottas disease; Charcot-Marie-Tooth disease, type 4F AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10848494; 11523566; 11157804; 12112076; 16534116; 21079185; 22847150 PSAP 9498 5660 Krabbe disease, atypical; Combined saposin deficiency; Gaucher disease, atypical, due to saposin C deficiency; Metachromatic leukodystrophy due to saposin-b deficiency AR N/A N/A Biochemical; Gastrointestinal; Musculoskeletal; Neurologic General BMT has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 41211; 6126151; 2060627; 3024666; 2615292; 2514102; 2764035; 1371116; 8460394; 8554069; 9672525; 9930900; 10682309; 11309366; 15856305; 15773042; 17919309; 19267410; 19955343; 20484222; 22652185 PSAT1 19129 29968 Phosphoserine aminotransferase deficiency AR Pediatric Allelic with Neu-Laxova syndrome 2 (AR) Biochemical; Craniofacial; Musculoskeletal; Neurologic Biochemical Neu-Laxova syndrome can involve multiple congenital anomalies Medical treatment (eg, with serine and glycine) can lead to improved outcomes, and early initiation of treatment may be beneficial 17436247; 25152457; 29269105 PSEN1 9508 5663 Cardiomyopathy, dilated 1U AD Pediatric Allelic with Acne inversa, familial, 3 (AD); Dementia, frontotemporal (AD/AR); Pick disease (AD); Alzheimer disease 3 (AD) Cardiovascular; Dermatologic; Neurologic Cardiovascular The reported onset of heart failure has been in the adult period (including in young adults), but surveillance and early treatment may be indicated prior to adulthood Surveillance (eg, with echocardiography), preventive measures and medical management may be helpful to decrease morbidity 7550356; 7596406; 7585193; 9052708; 9384602; 9521418; 9544835; 11094121; 11389157; 11524469; 12891668; 12668610; 15122701; 16216949; 16033913; 17186461; 20194882; 20929727; 21495993; 21656036 PSEN2 9509 5664 Cardiomyopathy, dilated, 1V; Peripartum/pregnancy-associated cardiomyopathy AD Pediatric Allelic with Alzheimer disease, 4 (AD) Cardiovascular; Neurologic; Obstetric Cardiovascular; Obstetric Preventive measures and medical management may be helpful to help decrease morbidity; Precautions/surveillance may be beneficial prior to/during pregnancy 7638622; 7651536; 9521418; 10822446; 11723295; 14681895; 12925374; 14623725; 17186461; 18427071; 20458009; 20457965 PSENEN 30100 55851 Acne inversa, familial, 2, with or without Dowling-Degos disease AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20929727; 28287404; 28601418 PSMA3 9532 5684 Proteasome-associated autoinflammatory syndrome 2 Digenic Pediatric Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Digenic inheritance has been reported Individuals may have recurrent infections, and awareness may allow preventative measures as well as prompt and agressive treatment of infections 26524591 PSMB10 9538 5699 Proteasome-associated autoinflammatory syndrome 5 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious The condition involves autoinflammatory manifestations, and medical management (eg, with steroids and methotrexate) has been described as beneficial 31783057 PSMB4 9541 5692 Proteasome-associated autoinflammatory syndrome 3 AR/Digenic Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Digenic inheritance has been reported Individuals may have recurrent infections, and awareness may allow preventative measures as well as prompt and agressive treatment of infections 26524591 PSMB8 9545 5696 Proteasome-associated autoinflammatory syndrome 1 AR/Digenic Pediatric Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Cardiovascular Digenic inheritance has been reported Individuals may have recurrent infections, and awareness may allow preventative measures as well as prompt and agressive treatment of infections; Individuals have been described with multiple manifestations, including lethal arrhythmias, and surveillance may allow early detection and management of cardiac sequelae 6499339; 4026345; 3618123; 8495043; 21129723; 20534754; 20159315; 21852578; 21881205; 21953331; 22441638; 26524591 PSMB9 9546 5698 Proteasome-associated autoinflammatory syndrome 3 Digenic Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal Allergy/Immunology/Infectious Digenic inheritance has been reported Individuals may have recurrent infections, and awareness may allow preventative measures as well as prompt and agressive treatment of infections 26524591 PSMC3 9549 5702 Deafness, cataract, impaired intellectual development, and polyneuropathy AR N/A N/A Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Ophthalmologic General Cochlear implants were not described as effective Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32500975 PSMC3IP 17928 29893 Ovarian dysgenesis 3 AR Pediatric Endocrine; Genitourinary General To induce/maintain secondary sex characteristics, and to allow reproduction, specific interventions (eg, medical hormonal treatment) may be necessary Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21963259 PSMD12 9557 5718 Stankiewicz-Isidor syndrome AD N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28132691 PSMG2 24929 56984 Proteasome-associated autoinflammatory syndrome 4 AR Pediatric Allergy/Immunology/Infectious; Neurologic Allergy/Immunology/Infectious The condition involves autoinflammatory manifestations, and medical management (eg, with JAK inhibitors) has been described as resulting in clinical improvement 30664889 PSPH 9577 5723 Phosphoserine phosphatase deficiency AR Pediatric Biochemical; Neurologic Biochemical Medical treatment (eg, with L-serine, glycine) has been reported as beneficial in terms of both biochemical parameters and clinical manifestations (head growth) 9222972; 14673469; 16763900; 19963421; 25080166 PSTPIP1 9580 9051 Pyogenic sterile arthritis, pyoderma gangrenosum, and acne AD Pediatric Allergy/Immunology/Infectious; Dermatologic; Endocrine; Musculoskeletal Allergy/Immunology/Infectious; Pharmacogenomic Medical treatment (eg, anakinra) can be effective to treat autoimmune manifestations; Cytopenia related to sulfonamide use has been reported 9212761; 11971877; 19673875; 21790734 PTCD3 24717 55037 Combined oxidative phosphorylation deficiency 51 AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30607703; 30706245 PTCH1 9585 5727 Basal cell nevus syndrome AD Pediatric Variants may also be associated with Holoprosencephaly (AD), though evidence for pathogenicity is mixed (individuals with holoprosencephaly can manifest with endocrine anomalies such as diabetes insipidus, but the efficacy of early diagnosis is unclear) Craniofacial; Dermatologic; Endocrine; Musculoskeletal; Neurologic; Oncologic Oncologic Individuals are at risk for a number of types of malignancies, including basal cell carcinomas and medulloblastoma , as well as (rare) malignant rare keratocyst transformation, and awareness and surveillance may allow early diagnosis and treatment (including with molecular therapies that target the Hedgehog signaling pathway), potentially reducing morbidity and mortality; Avoidance of agents such as radiation therapy is indicated 13851319; 8326488; 9096761; 9096762; 8981943; 11382639; 11941477; 16906569; 19439922; 19557015; 21368767; 22007994; 22565648; 22670903; 22670904; 22844361; 23677114 PTCH2 9586 8643 Basal cell nevus syndrome AD Pediatric Dermatologic; Musculoskeletal; Oncologic Oncologic Individuals are at risk for a number of types of malignancies, including basal cell carcinomas and medulloblastoma , as well as (rare) malignant rare keratocysttransformation, and awareness and surveillance may allow early diagnosis and treatment (including with molecular therapies that target the Hedgehog signaling pathway), potentially reducing morbidity and mortality; Avoidance of agents such as radiation therapy is indicated 18285427; 22670903; 22670904; 23479190 PTCHD1 26392 139411 Autism susceptibility, X-linked 4 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18252227; 21091464; 25131214 PTDSS1 9587 9791 Lenz-Majewski hyperostotic dwarfism AD N/A N/A Craniofacial; Dental; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24241535 PTEN 9588 5728 PTEN hamartoma tumor syndrome; Cowden syndrome 1; Bannayan-Riley-Ruvalcaba syndrome; Lhermitte-Duclos syndrome; Glioma susceptibility 2; Meningioma, familial; Endometrial cancer AD Pediatric Allelic with Macrocephaly/autism syndrome (AD) (without reported associated malignancies); Reported as allelic with VACTERL association with hydrocephalus (AD) Craniofacial; Dermatologic; Neurologic; Oncologic Oncologic Evidence for association with some cancerous processes is unclear,and the division into many separate disorders is likely specious Surveillance is indicated to screen for the presence of neoplasms (including regular thyroid ultrasound, dermatologic examinations, breast screening including mammogram and/or MRI, transvaginal ultrasound and/or endometrial biopsy, colonoscopy, renal imaging, and other screening as specifically indicated by family or personal medical history), which may allow early diagnosis and treatment, which may be beneficial related to morbidity and mortality 5345120; 5091590; 957004; 7449178; 7079022; 6881215; 6507473; 3707175; 3698331; 3340479; 1336932; 1350505; 8207516; 9140396; 9286463; 9399897; 9241266; 9259288; 9545417; 9662392; 9832032; 9832031; 9425889; 9445133; 9856571; 10353779; 10400993; 10234502; 11238682; 11748304; 12085208; 11875759; 12938083; 14518069; 12833416; 14566704; 15805158; 16704655; 16752378; 17286265; 17526800; 17526801; 17847000; 18781191; 21659347; 21633361; 20301661; 21956414; 22595938; 22970944; 23335809; 23344409 PTF1A 23734 256297 Pancreatic and cerebellar agenesis; Pancreatic agenesis 2 AR Pediatric Craniofacial; Gastrointestinal; Neurologic; Ophthalmologic Endocrine The condition can include multiple congenital anomalies As the conditions can include pancreatic insufficiency, awareness can allow measures to manage neonatal diabetes as well as pancreatic exocrine insufficiency 10507728; 15543146; 19650412; 21749365; 24212882 PTH 9606 5741 Hypoparathyroidism, familial isolated 1 AD/AR Pediatric Endocrine Endocrine Early recognition of electrolyte abnormalitities (eg, hypocalcemia) can allow prompt treatment in order to avoid severe sequelae 3005800; 2212001; 1302009; 10523031 PTH1R 9608 5745 Eiken syndrome; Chondrodysplasia, Blomstrand type; Metaphyseal chondrodysplasia, Murk Jansen type; Failure of tooth eruption, primary AD/AR N/A N/A Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3975110; 6734674; 8276022; 7701349; 9268097; 9178745; 9649554; 9745456; 10664159; 12357475; 15525660; 17164305; 19061984; 20135246; 29987841 PTHLH 9607 5744 Brachydactyly, type E2 AD N/A N/A Dental; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20170896 PTPN11 9644 5781 Noonan syndrome 1; LEOPARD syndrome 1 AD Pediatric Allelic with Metachondromatosis (AD) Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Cardiovascular; Hematologic; Oncologic; Renal Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis, hypertrophic cardiomyopathy, and arrhythmias) can be beneficial; Can include bleeding diathesis, and recognition and preventive measures (eg, in surgical situations) can be beneficial; Individuals appear to be at increased risk for malignancy, and although specific surveillance may not be warranted, awareness may allow prompt detection and treatment; Awareness of increased risk of renal anomalies and hydronephrosis can allow prophylaxis and early and aggressive management of related manifestations (eg, infections) 19994192; 5921856; 5638719; 5771505; 4672553; 4547387; 7193405; 6602353; 6539946; 345952; 9222968; 3232698; 11316696; 11344190; 11704759; 12058348; 11992261; 12634870; 12529711; 12717436; 15384080; 15240615; 15985475; 15956085; 15723289; 15690106; 16523510; 16263833; 16358218; 17497712; 18203203; 18678287; 18241070; 19273734; 19054014; 20602484; 20954246; 20979190; 20876176; 20577567; 20301303; 21533187; 20954246; 21407260; 21534355; 22315187; 23799168; 23813970; 23885229; 23918208; 24034393; 24444506 PTPN14 9647 5784 Choanal atresia and lymphedema AR N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Craniofacial General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7158640; 1872518; 20826270 PTPN23 14406 25930 Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25558065; 27848944; 29090338; 29899372; 31395947 PTPRC 9666 5788 Severe combined immunodeficiency, autosomal recessive, T-cell negative, B-cell positive, NK cell positive AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been described 9068311; 11145714; 22689986 PTPRF 9670 5792 Breasts and/or nipples, aplasia or hypoplasia of, 2 AR N/A N/A Dermatologic; Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24781087 PTPRO 9678 5800 Nephrotic syndrome, type 6 AR N/A N/A Renal General Renal transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21722858 PTPRQ 9679 374462 Deafness, autosomal recessive 84 AR Pediatric Allelic with Deafness, autosomal dominant 73 (AD) Audiologic/Otolaryngologic Audiologic/Otolaryngologic In Deafness, autosomal dominant 73, the onset of hearing loss has been described as variable but typically postlingual Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 19888295; 20346435 PTRH2 24265 51651 Infantile-onset multisystem neurologic, endocrine, and pancreatic disease AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic Gastrointestinal The condition has been described as including exocrine pancreatic insufficiency, among other manifestatons, and awareness may allow medical management 25558065; 25574476; 27129381; 28328138; 33092935 PTS 9689 5805 Hyperphenylalaninemia, BH4-deficient, A AR Pediatric Biochemical; Neurologic Biochemical Dietary measures and/or medical treatment (eg, L-dopa, tetrahydrobiopterin) can be beneficial 7094929; 6142058; 3297709; 3308682; 8178819; 9222757; 9222755; 2027491; 11438997; 11916314; 1388593; 16364672; 20059486 PUF60 17042 22827 Verheij syndrome AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic; Renal General There is evidence that the condition may result from a deletion of multiple genes including PUF60 as well as heterozygous pathogenic variants in PUF60 alone Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19464398; 24140112 PUM1 14957 9698 Spinocerebellar ataxia 47 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29474920 PURA 9701 5813 Mental retardation, autosomal dominant 31 AD N/A N/A Craniofacial; Endocrine; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25342064; 25439098; 25533962 PUS1 15508 80324 Myopathy, lactic acidosis, and sideroblastic anemia 1 AR Pediatric Endocrine; Hematologic; Musculoskeletal; Neurologic Hematologic Severe, non-B6 responsive anemia has reportedly required transfusions 7726239; 14981724; 15108122; 15103716; 17056637; 19731322; 25227147 PUS3 25461 83480 Neurodevelopmental disorder with microcephaly and gray sclerae AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27055666; 28454995; 30308082; 32056211 PUS7 26033 54517 Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature AR N/A N/A Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30526862; 30778726 PXDN 14966 7837 Anterior segment dysgenesis 7 AR Pediatric Ophthalmologic Ophthalmologic Some individual are at risk of glaucoma, and surveillance and early treatment may be beneficial; Agents that may contribute to glaucoma should be avoided 21907015; 24939590 PYCR1 9721 5831 Cutis laxa, autosomal recessive, type IIB; Cutis laxa, autosomal recessive type IIIB AR N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4076251; 11424136; 16045708; 18304158; 18348262; 19576563; 19401719; 19648921; 21204221; 21567914; 21834030; 22052856 PYCR2 30262 29920 Leukodystrophy, hypomyelinating 10 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25865492 PYGL 9725 5836 Glycogen storage disease VI AR Pediatric Biochemical Biochemical The condition can include manifestations suc has hypoglycemia, ketosis, and growth retardation, and recommendations for care include laboratory-based monitoring (eg, including liver function tests, glucose, and ketones), radiological monitoring (abdominal imaging), and nutritional recommendations and avoidance of certain medications in order to help improve metabolic to control and prevent the primary complications; Specific care during pregnancy has been recommended 13646331; 5904467; 9529348; 9536091; 17705025; 20301788; 21646031; 25266922; 30659246 PYGM 9726 5837 Glycogen storage disease V AR Pediatric Biochemical; Musculoskeletal; Renal Biochemical; Musculoskeletal; Pharmacogenomic; Renal Avoidance of excessive exercise may be beneficial to avoid rhabdomyolysis and potential renal failure; Sucrose ingestion may be beneficial (eg, prior to exercise); Certain precautions should be taken with general anesthesia 16590445; 14442994; 4502558; 1067063; 101896; 6929403; 3808314; 3466902; 3207360; 2768781; 2391551; 8408630; 8316268; 11168025; 14695410; 16924035; 17705025; 17915571; 18667317; 19251976; 19433441; 20301518; 20957198; 21802952; 21880526; 22608882; 22818872; 22899091 PYROXD1 26162 79912 Myopathy, myofibrillar 8 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27745833 QARS1 9751 5859 Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24656866 QDPR 9752 5860 Hyperphenylalaninemia, BH4-deficient, C AR Pediatric Biochemical; Neurologic Biochemical Dietary measures and/or medical treatment (eg, L-dopa, tetrahydrobiopterin) can be beneficial 53532; 49470; 317358; 2785251; 2116088; 7627180; 10029353; 11153907; 11746132; 16917893 QRICH1 24713 54870 Ververi-Brady syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28692176; 30281152 QRICH2 25326 84074 Spermatogenic failure 35 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30683861 QRSL1 21020 55278 Combined oxidative phosphorylation deficiency 4 AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26741492; 29440775; 30283131 RAB11B 9761 9230 Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter AD N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29106825 RAB18 14244 22931 Warburg micro syndrome 3 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21473985 RAB23 14263 51715 Carpenter syndrome 1 AR N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dental; Endocrine; Genitourinary; Musculoskeletal; Neurologic General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19974019; 5935752; 3322002; 17503333; 20358613; 21082653; 21412941 RAB27A 9766 5873 Griscelli syndrome, type 2; Elejalde syndrome AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Hematologic; Neurologic; Oncologic Allergy/Immunology/Infectious; Oncologic Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; Surveillance for complications such as hemophagocytic lymphohistiocytosis to allow early medical treatment (with chemo-immunotherapy) may be beneficial in order to allow prompt medical treatment; HSCT has been described 707528; 7996360; 10835631; 12058346; 15452859; 17151879; 18350256; 18350256; 18397837; 18489042; 19030707; 19270433; 19953648; 20370853; 20591709; 21314004; 22111599; 23403622 RAB28 9768 9364 Cone-rod dystrophy 18 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23746546; 25356532 RAB33B 16075 83452 Dyggve-Melchior-Clausen syndrome; Smith-McCort dysplasia 2 AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22652534; 23042644 RAB39B 16499 116442 Waisman syndrome XL Pediatric Allelic with Mental retardation, X-linked 72 (XL) Craniofacial; Neurologic Neurologic Waisman syndrome has been reported as being responsive to levodopa 4025396; 11050621; 20159109; 25434005 RAB3GAP1 17063 22930 Warburg micro syndrome 1 AR Pediatric Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic Endocrine; Ophthalmologic; Pharmacogenomic The condition can include multiple congenital anomalies The condition can include a risk of glaucoma, and early treatment may be beneficial; Medical care related to endocrine manifestations may be indicated; Agents that may contribute to glaucoma should be avoided 8249951; 10465117; 11237903; 15216543; 15696165; 18286824; 20512159; 22768674 RAB3GAP2 17168 25782 Warburg micro syndrome 2; Martsolf syndrome AR Pediatric Cardiovascular; Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic Endocrine; Ophthalmologic; Pharmacogenomic The condition can include multiple congenital anomalies The condition can include a risk of glaucoma, and early treatment may be beneficial; Medical care related to endocrine manifestations may be indicated; Agents that may contribute to glaucoma should be avoided 677168; 16532399; 20967465 RAB7A 9788 7879 Charcot-Marie-Tooth disease, axonal, type 2B AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7573046; 9219740; 11094113; 12545426; 17060578; 22302274 RABL3 18072 285282 Pancreatic cancer, susceptibility to, 5 AD Adult Oncologic Oncologic Individuals are reported to be at increased risk of pancreatic cancer (as well as other neoplasms), and awareness may allow early diagnosis and management 31406347 RAC1 9801 5879 Neurologic AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28886345 RAC2 9802 5880 Immunodeficiency 73A with defective neutrophil chemotaxis and leukocytosis; Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopenia; Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinemia AD/AR Pediatric Allergy/Immunology/Infectious; Endocrine; Renal Allergy/Immunology/Infectious; Endocrine Renal transplant has been described in Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinemia Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial (neutrophil infusions have been described in Immunodeficiency 73A with defective neutrophil chemotaxis and leukocytosis) In Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopenia, HSCT has been described; Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinemia has been described as involving endocrine manifestations (eg, hypothyroidism, hyperparathyroidism), and awareness may allow early diagnosis and management 10758162; 10961859; 21167572; 25512081; 30654050; 30723080; 31071452; 31382036; 32542921 RAC3 9803 5881 Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies AD N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29276006; 30293988 RAD21 9811 5885 Cornelia de Lange syndrome 4 with or without midline brain defects; Mungan syndrome AD N/A N/A Cardiovascular; Craniofacial; Dental; Gastrointestinal; Neurologic; Ophthalmologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14638363; 17487221; 22633399; 25575569; 31334757 RAD50 9816 10111 Breast cancer, susceptibility to; Nijmegen breakage syndrome-like disorder AD/AR Adult (Breast cancer, susceptibility to); Pediatric (Nijmegen breakage syndrome-like disorder) Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic Audiologic/Otolaryngologic; Cardiovascular; Oncologic In Breast cancer, susceptibility to, awareness may allow surveillance, preventive measures, and early diagnosis and treatment of disease; Nijmegen breakage syndrome-like disorder has been described as involving sensorineural hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; An individual with Nijmegen breakage syndrome-like disorder has been described with arrhythmias, and awareness may allow early diagnosis and management of cardiac sequelae 14684699; 16474176; 1887849; 19092773; 19409520; 20571869; 21356067; 21799032; 22006311; 22048815; 22476849; 24549055; 24894818; 32212377 RAD51 9817 5888 Mirror movements 2; Fanconi anemia, complementation group R AD N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Individuals with Fanconi anemia, complementation group R have not been described with hematologic or oncologic manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21242494; 22305526; 26253028; 26681308 RAD51C 9820 5889 Breast-ovarian cancer, familial, susceptibility to; Fanconi anemia goup O AD/AR Pediatric (Fanconi anemia goup O); Adult (Breast-ovarian cancer, familial, susceptibility to) Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic The condition may include multiple congenital anomalies In Breast-ovarian cancer susceptibility, surveillance (similar to that indicated in individuals with BRCA1 or BRCA2 variants) may allow early detection and treatment of tumors, which may reduce morbidity and mortality; For Fanconia anemia, specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; surveillance for complications such as bone marrow failure is recommended 20400964; 20400963; 21568838; 20301575 RAD51D 9823 5892 Ovarian cancer, familial, susceptibility to AD Adult Oncologic Oncologic Surveillance (similar to that described for individuals with variants in BRCA1 or BRCA2) related to ovarian cancer may allow early diagnosis and treatment of neoplasms (eg, ovarian tumors), which may reduce morbidity and mortality; Specific, targeted therapies may be available 21822267; 23300655; 23372765 RAF1 9829 5894 Cardiomyopathy, dilated, 1NN; LEOPARD syndrome 2; Noonan syndrome 5 AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Hematologic; Musculoskeletal; Neurologic Cardiovascular; Hematologic In Dilated cardiomyopathy, individuals may present in pediatric without other syndromic findings, and awareness may allow early surveillance and management; In LEOPARD and Noonan syndromes, surveillance and treatment related to manifestations such as cardiac anomalies (which include hypertrophic cardiomyopathy) and short stature can be beneficial; Precautions regarding bleeding risk can be beneficial 17603483; 17603482; 20876176; 20602484; 20301303; 24777450 RAG1 9831 5896 T cell-negative, B cell-negative, natural killer cell-positive severe combined immunodeficiency; Omenn syndrome; Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity; Combined cellular and humoral immune defects with granulomas AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal Allergy/Immunology/Infectious Antiinfectious prophylaxis (though special consideration is necessary related to the use of live vaccines) and early and aggressive treatment of infections may be beneficial; HSCT has been reported 9630231; 10226883; 11313270; 16276422; 18463379; 20956421; 20489056; 21131235; 21624848; 21184155; 21732012; 21625022; 21771083; 22424479 RAG2 9832 5897 Omenn syndrome; Combined cellular and humoral immune defects with granulomas AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal Allergy/Immunology/Infectious Antiinfectious prophylaxis (though special consideration is necessary related to the use of live vaccines) and early and aggressive treatment of infections may be beneficial 9630231; 10226883; 16276422; 20128425; 18463379; 21624848; 21184155; 21625022 RAI1 9834 10743 Smith-Magenis syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12652298; 15788730; 16845274; 17539903; 21739587; 21897445; 22578325 RALA 9839 5898 Hiatt-Neu-Cooper neurodevelopmental syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30500825; 30761613 RALGAPA1 17770 253959 Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation AR Pediatric Craniofacial; Musculoskeletal; Neurologic; Pulmonary Pulmonary Among other findings, individuals have been described with neonatal respiratory insufficiency requiring intervention, and awareness may allow such interventions to be performed efficiently 32004447 RANBP2 9848 5903 Encephalopathy, acute, infection-induced, 3, susceptibility to AD Pediatric Allergy/Immunology/Infectious; Neurologic Allergy/Immunology/Infectious Early diagnosis could allow potentially beneficial measures, such as ensuring up-to-date immunization status (eg, against influenza), though full protection against all inciting agents would not be possible 12874403; 19118815; 19811512; 20473521; 21205700 RAPGEF2 16854 9693 Epilepsy, familial adult myoclonic, 7 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29507423 RAPSN 9863 5913 Myasthenic syndrome, congenital 11, associated with acetylcholine receptor deficiency AR Pediatric Allelic with Fetal akinesia deformation sequence 2 (AR) Musculoskeletal; Neurologic Musculoskeletal; Neurologic; Pharmacogenomic Prophylactic medications (anticholinesterase therapy) in order to prevent apneic episodes/sudden respiratory insufficiency secondary to fever/infections can be effective; Most individuals with CMS benefit from AChE inhibitors and/or potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; Some individuals with SCCMS are treated with quinidine, which has some major side effects and may be detrimental in individuals with AChR deficiency 12651869; 14504330; 15286164; 18179903; 18252226; 19261599; 20930056; 25194721; 25792100 RARB 9865 5915 Microphthalmia, syndromic 12 AD/AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17506106; 22686418; 24075189 RARS1 9870 5917 Leukodystrophy, hypomyelinating 9 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24777941 RARS2 21406 57038 Pontocerebellar hypoplasia, type 6 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17847012; 20635367; 22569581; 25809939 RASA1 9871 5921 Capillary malformation-arteriovenous malformation 1; Parkes Weber syndrome; Spinal arteriovenous anomalies AD Pediatric Cardiovascular; Musculoskeletal Cardiovascular Life-threatening complications of arteriovenous malformations and arteriovenous fistulas can include bleeding, congestive heart failure, and/or neurologic consequences, and surveillance may allow early detection and medical/surgical management, which may decrease morbidity/mortality 14639529; 15917201; 18363760; 18446851; 20007727; 21348050; 20821215; 22342634; 24038909 RASGRP1 9878 10125 Immunodeficiency 64 AR Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic The condition can involve early-onset recurrent bacterial, viral, and fungal infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals have been increased susceptibility to EBV infection and risk of EBV-associated lymphoma, and awareness may allow prompt diagnosis and management 27776107; 28822832; 29155103; 29282224 RASGRP2 9879 10235 Bleeding disorder, platelet-type, 18 AR Pediatric Hematologic Hematologic Individuals may demonstrate a bleeding diathesis (including postraumatic/postsurgical), and surveillance and prompt treatment of bleeding episodes may be beneficial 24958846 RAX 18662 30062 Microphthalmia, isolated 3 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14662654; 18783408; 22736936 RAX2 18286 84839 Cone-rod dystrophy 11 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15028672 RB1 9884 5925 Retinoblastoma AD Pediatric Oncologic Oncologic Frequent and regular eye examination (including under anesthesia if necessary) starting in infancy is indicated in order to detect ocular neoplasms, which may allow early detection and treatment; Awareness of the risk of additional neoplasms may allow early detection and treatment based on signs/symptoms (eg, bone pain); Limiting exposure to DNA-damaging agents (including high-dose radiotherapy) may be beneficial 1066869; 268552; 6930517; 6654325; 6696673; 2876425; 2885916; 2895471; 3175621; 7795591; 8651278; 9311732; 10502774; 10561222; 11097606; 11449317; 11709011; 11382640; 11382638; 12096963; 12523888; 12541220; 12488270; 12598449; 14996857; 16936756; 16631255; 16606893; 17613328; 17096365; 19280657; 20301625; 21150892; 22084214; 22103627; 22237022; 22293180; 22355046 RB1CC1 15574 9821 Schizophrenia AD N/A N/A Neurologic General Evidence or clinical applicability is unclear 21822266 RBBP8 9891 5932 Seckel syndrome 2; Jawad syndrome AR N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11781686; 18071751; 21998596; 24389050 RBCK1 15864 10616 Polyglucosan body myopathy 1 AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Cardiovascular Individuals have been described as being affected by recurrent and severe infections, and awareness may allow surveillance, prophylactic measures, and early and aggressive management of infections; Progressive dilated cardiomyopathy necessitating heart transplant has been described 23104095; 23798481; 23889995 RBM10 9896 8241 TARP syndrome XL N/A N/A Cardiovascular; Craniofacial; Musculoskeletal General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5410571; 20451169; 21910224; 24259342; 30189253 RBM12 9898 10137 Schizophrenia 19 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28628109 RBM20 27424 282996 Cardiomyopathy, dilated, 1DD AD Pediatric Cardiovascular Cardiovascular Surveillance (eg, with echocardiography and electrocardiography), preventive measures and medical management may help decrease morbidity; Cardiac transplantation has been described 19712804; 20590677; 21846512 RBM28 21863 55131 Alopecia, neurologic defects, and endocrinopathy syndrome AR Pediatric Dermatologic; Endocrine; Musculoskeletal; Neurologic Endocrine Features may include progressive endocrine abnormalities primarily related to progressive anterior pituitary hormone deficiency, including central adrenal insufficiency, as well as other endocrine deficiencies, and surveillance in order to allow appropriate hormonal replacement therapy may be beneficial 18439547; 20231366 RBMX 9910 27316 Mental retardation, X-linked, syndromic 11, Shashi type XL N/A N/A Audiologic/Otolaryngologic; Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10677307; 25256757 RBP3 9921 5949 Retinitis pigmentosa 66 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19074801 RBP4 9922 5950 Retinol dystrophy, iris coloboma, and comedogenic acne syndrome AR N/A N/A Dermatologic; Ophthalmologic General It has been suggested that high-dose vitamin A supplementation may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9888420; 2886863; 1293390; 23189188 RBPJ 5724 3516 Adams-Oliver syndrome 3 AD N/A N/A Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22883147 RC3H1 29434 149041 Immune dysregulation and systemic hyperinflammation syndrome AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Antibiotics or antiviral agents can be beneficial to treat/prevent infections that can trigger an exaggerated inflammatory response. Chemo/immunotherapy can achieve clinical stability prior to allogeneic hematopoietic cell transplantation (HCT), the only curative therapy. 31636267 RCBTB1 18243 55213 Retinal dystrophy with or without extraocular anomalies (RDEOA) AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27486781 RD3 19689 343035 Leber congenital amaurosis 12 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17186464; 20301475; 22531706; 23308101 RDH11 17964 51109 Microphthalmia, isolated, with coloboma 10; Retinal dystrophy, juvenile cataracts, and short stature syndrome AD/AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24916380; 25910211 RDH12 19977 145226 Leber congenital amaurosis 13; Retinitis pigmentosa 53 AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15258582; 15322982; 16269441; 17197551; 18779497; 19140180; 19840725; 20736127; 22065924 RDH5 9940 5959 Fundus albipunctatus AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10617778; 10369264; 11153648; 11812441; 16637847; 20829743; 21529959; 22669287; 22736946; 22815624 RDX 9944 5962 Deafness, autosomal recessive 24 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 17226784; 19215054 REC114 25065 283677 Oocyte maturation defect 10 AR N/A N/A Obstetric General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31704776 RECQL4 9949 9401 Baller-Gerold syndrome; RAPADILINO syndrome; Rothmund-Thomson syndrome AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Oncologic; Renal Oncologic While the disorders may be recognizable, individuals may be at risk for neoplasms, and awareness may allow early diagnosis and treatment, which may reduce morbidity and mortality 8160763; 10678659; 12838562; 12952869; 15964893; 18716613; 20113479; 20503338; 27247962; 27287744; 27859906; 28039508; 28358413; 28486640; 29224249; 29367366; 29462647; 29642415; 29659569; 30007837; 31406625; 31428572; 32482547 REEP1 25786 65055 Spastic paraplegia 31; Distal hereditary motor neuronopathy VB AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16826527; 18321925; 19034539; 22703882 REEP2 17975 51308 Spastic paraplegia 72, autosomal dominant; Spastic paraplegia 72, autosomal recessive AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24388663 REEP6 30078 92840 Retinitis pigmentosa 77 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27889058 RELA 9955 5970 Mucocutaneous ulceration, chronic AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals can have chronic mucocutaneous ulcerations, and medical management (with a tumor necrosis factor inhibitor) has been described as beneficial 28600438 RELB 9956 5971 Immunodeficiency 53 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described with recurrent respiratory and other infections, and awareness may allow preventative measures and early and aggressive treatment of infections; HSCT has been described 26385063; 28552761 RELN 9957 5649 Epilepsy, familial temporal lobe, 7; Lissencephaly 2 AD/AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10973257; 17431900; 26046367 RELT 13764 84957 Amelogenesis imperfecta, type IIIC AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30506946 REN 9958 5972 Tubulointerstitial kidney disease, autosomal dominant, 4 AD Pediatric Allelic with Hyperproreninemia, familial (AD); Renal tubular dysgenesis (AR) Renal Pharmacogenomic; Renal Surveillance for hematologic (anemia) and renal (hyperuricemia, decreased renal function) disease may be beneficial to allow early medical management; Treatment of low plasma renin activity/low plasma concentration of aldosterone (eg, through management of sodium intake), as well as medical management of hyperkalemia (eg, with fludrocortisones, potassium restriction) may be beneficial, and may be indicated prior to the development of severe chronic kidney disease, though kidney transplantation may be necessary; Treatment of anemia (with erythropoietin) may be effective; Preventive treatment of hyperuricemia (eg, with allopurinol) and medical treatment of gout (eg, with prednisone, colchicines) may be effective; Certain agents should be avoided, including NSAIDS, ACE-inhibitors, dehydration, and specific dietary practices that can exacerbate gout 2017226; 7982942; 12634862; 16116425; 16164624; 19664745; 21084044; 21473025 REPS1 15578 85021 Neurodegeneration with brain iron accumulation 7 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29395073 RERE 9965 473 Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH) AD N/A N/A Cardiovascular; Craniofacial; Genitourinary; Neurologic; Ophthalmologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27087320 REST 9966 5978 Wilms tumor 6 AD Pediatric Allelic with Deafness, autosomal dominant 27 (AD); Fibromatosis, gingival, 5 (AD) Audiologic/Otolaryngologic; Dental; Oncologic Oncologic Surveillance and early detection of and treatment for Wilms tumor may decrease morbidity and mortality 18279434; 26551668; 28686854; 29961578 RET 9967 5979 Central hypoventilation syndrome, congenital; Multiple endocrine neoplasia, type IIA; Multiple endocrine neoplasia, type IIB; Medullary thyroid carcinoma, familial; Pheochromocytoma; Hirschsprung disease, susceptibility to 1 AD/AR Pediatric Allelic with Renal agenesis (AD) Endocrine; Gastrointestinal; Neurologic; Oncologic; Renal Endocrine; Gastrointestinal; Neurologic; Oncologic In Central hypoventilation syndrome the data are mixed related to causality (eg, one reported patient was later found to have a variant in a gene with more evidence for involvement in the condition) Surveillance/early diagnosis for and treatment of associated neoplasms (eg, including thyroidectomy at an early age, and diagnosis and treatment of sequelae of pheochromocytoma) may reduce morbidity and mortality; Due to risk of Hirschsprung disease, awareness of disease risk may allow prompt diagnosis and treatment, decreasing potential morbidity and mortality; In Central Hypoventilation, early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality 5844561; 4957444; 6047980; 5637238; 4968712; 4386574; 4695886; 1110583; 980061; 1063979; 554522; 3697657; 2904651; 2563193; 8103403; 8094268; 8099202; 7906417; 7977365; 7914213; 7815416; 7911697; 7906866; 7907913; 8114938; 7915165; 7633441; 7581377; 7784092; 7845675; 8825918; 8826440; 8852653; 8757765; 9111992; 9097963; 8981969; 9090527; 9497256; 9506724; 9384613; 9621513; 9824583; 9760196; 10090908; 10528857; 10521317; 10323403; 10458491; 10522989; 10922382; 11103773; 10777380; 10982477; 11739416; 11436122; 11753660; 11238493; 11502806; 11232007; 12116277; 11953745; 12355085; 12214285; 12086152; 11815959; 11932300; 11788682; 12000816; 12466368; 14561794; 14602786; 14600022; 12788868; 15138456; 15240649; 15759212; 16091499; 15829955; 15805159; 15870131; 15741265; 15827097; 16162881; 16205644; 16443855; 17108762; 17167516; 17895320; 16986122; 17898100; 18252215; 18273880; 19469690; 19856714; 20301434; 20598273; 22715565; 23114404 RETREG1 25964 54463 Neuropathy, hereditary sensory and autonomic, type IIB AR N/A N/A Neurologic General Insensitivity to pain can result in injuries and infections Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19838196; 24327336 RFC1 9969 5981 Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30926972; 32851396 RFT1 30220 91869 Congenital disorder of glycosylation, type In AR Pediatric Biochemical; Gastrointestinal; Hematologic; Neurologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 9516657; 10801058; 18313027; 19701946 RFWD3 25539 55159 Fanconi anemia, complementation group W AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Renal Allergy/Immunology/Infectious; Endocrine; Hematologic; Oncologic Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Growth hormone insufficiency has been described, and awareness may allow early treatment; Surveillance for complications such as bone marrow failure is recommended 20301575; 28691929 RFX5 9986 5993 Bare lymphocyte syndrome, type II AR Pediatric Allergy/Immunology/Infectious; Gastrointestinal Allergy/Immunology/Infectious Prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been reported in Bare lymphocyte syndrome, type II 7744245; 9401005; 10079298; 12368908 RFX6 21478 222546 Pancreatic hypoplasia, intestinal atresia, and gallbladder aplasia or hypoplasia, with or without tracheoesophageal fistula; Martinez-Frias syndrome; Mitchell-Riley syndrome AR Pediatric Endocrine; Gastrointestinal Endocrine; Gastrointestinal While the condition may be recognizable, prompt treatment of gastrointestinal (including pancreatic) issues would be beneficical 10528254; 15592663; 18512226; 19887127; 20148032; 21965172; 22662242; 23914949; 26264437 RFXANK 9987 8625 MHC class II deficiency AR Pediatric Allergy/Immunology/Infectious; Gastrointestinal Allergy/Immunology/Infectious Prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been reported in Bare lymphocyte syndrome, type II 7951244; 9806546; 11313409; 12618906; 20414676; 21908431 RFXAP 9988 5994 Bare lymphocyte syndrome, type II AR Pediatric Allergy/Immunology/Infectious; Gastrointestinal Allergy/Immunology/Infectious Prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been reported in Bare lymphocyte syndrome, type II 650344; 7021490; 9118943; 20197681 RGR 9990 5995 Retinitis pigmentosa 44 AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10581022 RGS9 10004 8787 Bradyopsia AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1790747; 14702087; 17826834 RGS9BP 30304 388531 Bradyopsia AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14702087 RHAG 10006 6005 Overhydrated hereditary stomatocytosis; Anemia, hemolytic, Rh-null, regulator type; Anemia, hemolytic,Rh-Mod type; RHAG blood group AD/AR/BG Pediatric Hematologic Hematologic Individuals can suffer severe anemia, which can be ameliorated by splenectomy (though splenectomy may be less beneficial in Overhydrated hereditary stomatocytosis); Individuals with Overhydrated hereditary stomatocytosis may be prone to iron overload as well as postsplenectomy thrombotic complications, and awareness may allow surveillance and management; Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 4628355; 3103426; 8563755; 8639421; 9442063; 9454778; 9746795; 9915949; 10467273; 11961248; 18931342; 19744193 RHBDF2 20788 79651 Tylosis with esophageal cancer AD Adult Dermatologic; Gastrointestinal; Oncologic Oncologic Surveillance and early detection of and treatment for malignancy may decrease morbidity and mortality; Individuals may be at especially high risk of esophageal cancer with tobacco use 13209063; 8508402; 8666405; 8651714; 22265016 RHCE 10008 6006 Rhesus blood group BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 1824267; 8220426; 9657769 RHO 10012 6010 Retinitis pigmentosa 4; Retinitis punctata albescens; Night blindness, congenital stationary, autosomal dominant 1 AD/AR N/A N/A Ophthalmologic General Oral vitamin A may slow retinal degeneration in some forms of retinitis pigmentosa Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2613244; 2137202; 2215617; 2333895; 1882937; 1302614; 1301135; 8512476; 8358437; 7846071; 8841304; 9197578; 9888392; 10980774; 20301590; 20555336; 21174529; 22419850 RHOA 667 387 Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies AD N/A N/A Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic General Causative variants have been postzygotic mosaic (and not detected via blood-based testing) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31570889 RHOBTB2 18756 23221 Developmental and epileptic encephalopathy 64 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29276004 RHOH 686 399 Epidermodysplasia verruciformis, susceptibility to, 4 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Oncologic Allergy/Immunology/Infectious; Oncologic Individuals have been described with susceptibility to certain infections as well as potential increased risk of malignancy, and awareness may allow prompt diagnosis and management of sequeleae 22850876 RIC1 17686 57589 Cleft lip, cataract, tooth abnormality, intellectual disability, facial dysmorphism, and attention-deficit hyperactivity disorder (CATIFA syndrome) AD N/A N/A Craniofacial; Dental; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27878435; 31932796 RIMS1 17282 22999 Cone-rod dystrophy 7 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9634506; 12659814 RIMS2 17283 9699 Cone-rod synaptic disorder syndrome, congenital nonprogressive AR Pediatric N/A Endocrine; Neurologic; Ophthalmologic Endocrine Among other features, metabolic dysfunction (including hyperglycemia and insulin resistance) has been described and suggested as an age-related manifestation, and awareness may allow early identification and management 32470375 RIN2 18750 54453 Macrocephaly, alopecia, cutis laxa, and scoliosis AR N/A N/A Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19631308; 20424861; 21431621; 23963297;24449201 RINT1 21876 60561 Infantile liver failure syndrome 3 AR N/A N/A Gastrointestinal; Musculoskeletal General Liver transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31204009 RIPK1 10019 8737 Autoinflammation with episodic fever and lymphadenopathy; Immunodeficiency 57 with autoinflammation AD/AR Pediatric Allergy/Immunology/Infectious; Gastrointestinal Allergy/Immunology/Infectious Autoinflammation with episodic fever and lymphadenopathy may involve recurrent fevers and accompanying symptoms, and medical management (eg, with anti-IL6R treatment) has been desrcribed as beneficial; Immunodeficiency 57 can include early-onset, recurrent bacterial, viral, and fungal infections, and awareness preventative measures and early and aggressive treatment of infections (e.g., IVIG has been described as beneficial); HSCT has been described 30026316; 31827280; 31827281 RIPK4 496 54101 Bartsocas-Papas syndrome 1; CHAND syndrome AR N/A N/A Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4339984; 10925380; 15264293; 23074676; 22197489; 22197488; 26129644; 28940926 RIPOR2 13872 9750 Deafness, autosomal recessive 104 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 24958875 RIPPLY2 21390 134701 Spondylocostal dysostosis, autosomal recessive 6 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25343988 RIT1 10023 6016 Noonan syndrome 8 AD Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Oncologic Cardiovascular; Oncologic Surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis and hypertrophic cardiomyopathy as well as congenital heart defects ) can be beneficial; Individuals may be at increased risk for malignancy (a child with ALL has been described), and although specific surveillance may not be warranted, awareness may allow prompt detection and treatment 23791108; 24939608; 25124994 RLBP1 10024 6017 Newfoundland rod-cone dystrophy; Bothnia retinal dystrophy; Retinitis punctata albescens; Fundus albipunctatus AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10102298; 11176989; 11868161; 14718298; 18344446; 20301590; 21447491; 22551409 RLIM 13429 51132 Tonne-Kalscheuer syndrome XL N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25644381; 25735484; 29728705 RMND1 21176 55005 Combined oxidative phosphorylation deficiency 11 AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18835491; 23022098; 23022099; 25058219 RMRP 10031 6023 Anauxetic dysplasia 1; Cartilage-hair hypoplasia; Metaphyseal dysplasia without hypotrichosis AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic Allergy/Immunology/Infectious; Hematologic; Oncologic There is a wide range of manifestations and severity, and while the disorder may be frequently (though not always) easily clinically recognizable, there is an increased risk reported of hematologic, immunologic, and oncologic complications, and surveillance and prompt treatment may be beneficial; HSCT has been described 14284412; 3521972; 1743218; 1789294; 1442902; 1290847; 1404295; 8444246; 9809821; 10494084; 10064668; 11207361; 11940090; 16252239; 16097009; 16832578; 18280854; 18698627; 18280853; 19150606; 20375313; 20538026; 21063072; 22420014; 22987807; 30561899 RNASEH1 18466 246243 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive, 2 AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26094573 RNASEH2A 18518 10535 Aicardi-Goutieres syndrome 4 AR N/A N/A Cardiovascular; Gastrointestinal; Dermatologic; Cardiovascular; Hematologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16845400; 17846997; 20301648 RNASEH2B 25671 79621 Aicardi-Goutieres syndrome 2 AR N/A N/A Cardiovascular; Gastrointestinal; Dermatologic; Hematologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9706629; 16845400; 20301648; 25243380 RNASEH2C 24116 84153 Aicardi-Goutieres syndrome 3 AR N/A N/A Cardiovascular; Gastrointestinal; Dermatologic; Hematologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16845400; 17846997; 20301648; 23322642 RNASEL 10050 6041 Prostate cancer, hereditary, 1 AD Adult Oncologic Oncologic Variants may be involved in susceptibility to multiple cancer types Surveillance and early diagnosis could potentially be beneficial 11799394; 12022038; 12915880; 16054567; 17224235; 18575592 RNASET2 21686 8635 Leukoencephalopathy, cystic, without megalencephaly AR Pediatric Audiologic/Otolaryngologic; Neurologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may possibly benefit developmental outcomes in some individuals, including speech and language development 9810556; 11589166; 15851732; 19525954 RNF113A 12974 7737 Trichothiodystrophy 5, nonphotosensitive XL Pediatric Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Endocrine; Genitourinary; Musculoskeletal; Neurologic Allergy/Immunology/Infectious The condition can involve recurrent infections, and awareness may allow preventive measures, and early and aggressive treatment of infections 19377476; 25612912; 31130284; 31880405 RNF125 21150 54941 Tenorio syndrome AD N/A N/A Allergy/Immunology/Infectious; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25196541 RNF13 10057 11342 Developmental and epileptic encephalopathy 73 AD N/A N/A Audiologic/Otolaryngologic; Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30595371 RNF135 21158 84282 Macrocephaly, macrosomia, facial dysmorphism syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17632510 RNF139 17023 11236 Renal cell carcinoma, clear cell AD Pediatric Oncologic Oncologic Genomic disruptions have been reported Surveillance and early detection of and treatment for malignancy (a number of cancer types have been described, including renal cell cancer and dysgerminoma) may decrease morbidity and mortality 17539022; 19642973 RNF168 26661 165918 RIDDLE syndrome AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic; Oncologic Allergy/Immunology/Infectious; Oncologic It has been suggested that heterozygotes may demonstrate an increased risk of oncologic processes as well Individuals have been described with immunodefiency, as well as radiosensitivity, and thus preventive measures and prophylaxis and early and aggressive treatment of infections may be warranted 17940005; 19203578; 21394101 RNF170 25358 81790 Ataxia, sensory, 1, autosomal dominant AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17190954; 21115467 RNF213 14539 57674 Moyamoya disease 2 AD/AR Adult Cardiovascular Cardiovascular Individuals with biallelic variants typically have earlier onset of manifestations The condition can manifest with transient ischemic attacks, cerebral infarction, and intracranial hemorrhage, and surveillance, preventive measures and early medical treatment may ameliorate/prevent severe sequelae 21048783; 22377813; 22931863 RNF216 21698 54476 Cerebellar ataxia and hypogonadotropic hypogonadism (Gordon Holmes syndrome) AR Pediatric Endocrine; Neurologic Endocrine Individuals have been described with response to medical treatment (eg, exogenous GnRH therapy), though with progressive loss of pituitary function such that response to treatment decreased and was lost later in the course of disease 11932290; 23656588 RNF43 18505 54894 Sessile serrated polyposis cancer syndrome AD Adult Oncologic Oncologic Individuals are at high risk of developing colorectal cancer (and possibly additional neoplasms), and awareness may allow surveillance and early surgical and medical management of neoplasms 24512911; 27081527 RNPC3 18666 55599 Isolated growth hormone deficiency, type V AR Pediatric Endocrine Endocrine Individuals may respond to GH treatment, and awareness may allow prompt management 24480542; 29866761 RNU4ATAC 34016 100151683 Roifman syndrome AR Pediatric Allelic with Microcephalic osteodysplastic primordial dwarfism, type I (Taybi-Linder syndrome) (AR); Lowry-Wood syndrome (AR) Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal Allergy/Immunology/Infectious Among other features, individuals with Roifman syndrome have been described with antibody deficiency and recurrent and severe infections, and awareness may allow preventive measures and early and aggressive treatment of infections 934161; 984702; 9800907; 10189087; 12571786; 21474760; 21474761; 22581640; 25735804; 26522830; 29265708; 30368667 ROBO2 10250 6092 Vesicoureteral reflux 2 AD Pediatric Renal Renal Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function 17357069 ROBO3 13433 64221 Gaze palsy, familial horizontal, with progressive scoliosis 1 AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15105459; 16525029; 18829051; 19633821; 21592015; 21850172 ROBO4 17985 54538 Aortic valve disease 3 AD Pediatric Cardiovascular Cardiovascular Individuals may have aortic valve and related anomalies (some of which may require surgery), and awareness may allow early diagnosis and management 30455415 ROGDI 29478 79641 Kohlschutter-Tonz syndrome AR N/A N/A Dental; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4372200; 16411202; 22482807; 22424600 ROM1 10254 6094 Retinitis pigmentosa 7, digenic Digenic N/A N/A Ophthalmologic General Digenic inheritance (with PRPH2) has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8202715; 1684223 ROR1 10256 4919 Deafness, autosomal recessive 108 AR Pediatric N/A Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may possibly benefit developmental outcomes in some individuals, including speech and language development 27162350 ROR2 10257 4920 Robinow syndrome, autosomal recessive; Brachydactyly, type B1 AD/AR N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10700182; 10932186; 10932187; 10986040; 12919145; 15952209; 17256787; 18831060; 19461659; 22178368; 23238279; 24932600; 24954533; 26284319; 30143665; 31617258; 32172608 RORA 10258 6095 Intellectual developmental disorder with or without epilepsy or cerebellar ataxia AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29656859 RORB 10259 6096 Epilepsy, idiopathic generalized, susceptibilty to, 15 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27352968 RORC 10260 6097 Immunodeficiency 42 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Indiviiduals have been described as having increased susceptibility to mycobacterial and candidal infections, as well as disseminated mycobacterial infections after BCG vacciination, and awareness may allow preventive measures, and early and aggressive treatment of infections 26160376 RP1 10263 6101 Retinitis pigmentosa 1, autosomal dominant; Retinitis pigmentosa 1, autosomal recessive AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1783394; 10391211; 10391212; 18552984; 19933189; 20664799; 21746989; 22052604; 22317909; 22321012; 22917891; 23077400 RP1L1 15946 94137 Occult macular dystrophy; Retinitis pigmentosa 88 AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2774037; 8909203; 10670483; 12664360; 17317401; 20826268; 22466457; 23281133 RP2 10274 6102 Retinitis pigmentosa 2 XL N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9697692; 10053026; 10942419; 11462235; 12417528; 20021257; 20625056; 21738648 RP9 10288 6100 Retinitis pigmentosa 9 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8513323; 12032732 RPE65 10294 6121 Retinitis pigmentosa 20; Leber congenital amaurosis 2 AR Pediatric Allelic with Retinitis pigmentosa 87 with choroidal involvement (AD) Ophthalmologic Ophthalmologic Gene therapy has been described, with increased effectiveness when instituted early 13616783; 9326941; 9326927; 9501220; 12960219; 14962443; 15557452; 18441371; 18809924; 19675341; 18441370; 18774912; 19854499; 20006823; 22323828; 22644094; 23341016; 23341635; 23474247; 27375040; 28712536; 29033008 RPGR 10295 6103 Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness XL Pediatric Allelic with Cone-rod dystrophy, X-linked, 1 (XL); Macular degeneration, X-linked atrophic (XL); Retinitis pigmentosa 3 (XL) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Ophthalmologic Allergy/Immunology/Infectious; Audiologic/Otolaryngologic Individuals can have hearing loss, some of which may be attributed to recurrent ear infections Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial: Individuals may demonstrate hearing loss at a relatively young age, and interventions related to recognition and management of hearing impairment may be beneficial 1733835; 7611300; 8673101; 8817343; 9350809; 9399904; 9443860; 10094550; 10970770; 10932196; 12160730; 11857109; 11950860; 11875055; 14627685; 14564670; 12657579; 12920075; 15914600; 16387007; 16055928; 17480003; 21857984; 21866333; 22183348; 24043777 RPGRIP1 13436 57096 Leber congenital amaurosis 6; Cone-rod dystrophy 13 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11283794; 11528500; 12920076; 20006823; 20301475 RPGRIP1L 29168 23322 COACH syndrome 3 AR N/A Allelic with Meckel syndrome 5 (AR); Joubert syndrome 7 (AR) Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal Gastrointestinal In COACH syndrome, among other findings, individuals may have hepatic disease, and it has been suggested that identification of liver disease is critical as some patients may develop complications such as portal hypertension with fatal variceal bleeding 17558407; 17558409; 18565097; 19430481; 19574260; 20301500 RPIA 10297 22934 Ribose 5-phosphate isomerase deficiency AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14988808 RPL10 10298 6134 Mental retardation, X-linked, syndromic, 35 XL N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25316788; 25846674; 26290468 RPL11 10301 6135 Diamond-Blackfan anemia 7 AD Pediatric Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Oncologic; Renal Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may allow early detection and management; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 16317735; 19061985; 20301769; 23718193; 23812780 RPL13 10303 6137 Spondyloepimetaphyseal dysplasia, Isidor-Toutain type AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23956136; 31630789 RPL15 10306 6138 Diamond-Blackfan anemia 12 AD Pediatric Cardiovascular; Hematologic; Musculoskeletal; Neurologic; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 20301769; 23812780 RPL18 10310 6141 Diamond-Blackfan anemia 18 AD Pediatric Hematologic; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may be beneficial 28280134 RPL21 10313 6144 Hypotrichosis 12 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19751230; 21412954 RPL26 10327 6154 Diamond-Blackfan anemia 11 AD Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Oncologic; Renal Hematologic; Oncologic Individuals may manifest with severe, transfusion dependent anemia, as well as profound neutropenia, and medical treatment (eg, with corticosteroids) has been reported as beneficial; Surveillance for and early treatment of malignancy may allow early detection and management; Awareness of the hearing loss may allow early interventions related to speech and language development; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 16317735; 17186470; 18535205; 19061985; 20116044; 20301769; 22431104 RPL27 10328 6155 Diamond-Blackfan anemia 16 AD Pediatric Cardiovascular; Hematologic; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 25424902 RPL35 10344 11224 Diamond-Blackfan anemia 19 AD Pediatric Hematologic; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may be beneficial 28280134 RPL35A 10345 6165 Diamond-Blackfan anemia 5 AD Pediatric Craniofacial; Hematologic; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 16317735; 18535205; 20301769; 23812780 RPL5 10360 6125 Diamond-Blackfan anemia 6 AD Pediatric Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Oncologic; Renal Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 16317735; 5764780; 19061985; 20301769; 23718193; 23812780 RPS10 10383 6204 Diamond-Blackfan anemia 9 AD Pediatric Craniofacial; Hematologic; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 16317735; 20116044; 20301769; 23812780 RPS15A 10389 6210 Diamond-Blackfan anemia 20 AD Pediatric Hematologic; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may be beneficial 28280134 RPS17 10397 6218 Diamond-Blackfan anemia 4 AD Pediatric Craniofacial; Hematologic; Musculoskeletal; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; Surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 16317735; 17647292; 19061985; 20301769; 23718193; 23812780 RPS19 10402 6223 Diamond-Blackfan anemia 1 AD Pediatric Cardiovascular; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 13722603; 16317735; 276838; 273451; 1958491; 8826887; 9988267; 10541318; 10590074; 16741228; 19061985; 20301769; 23812780; 23812780 RPS23 10410 6228 Brachycephaly, trichomegaly, and developmental delay AD N/A N/A Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26982655; 28257692 RPS24 10411 6229 Diamond-Blackfan anemia 3 AD Pediatric Cardiovascular; Craniofacial; Hematologic; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 16317735; 17186470; 20301769 RPS26 10414 6231 Diamond-Blackfan anemia 10 AD Pediatric Craniofacial;Hematologic; Musculoskeletal; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 16317735; 20116044; 20301769; 24942156 RPS27 10416 6232 Diamond-Blackfan anemia 17 AD Pediatric Dermatologic; Hematologic; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 25424902 RPS28 10418 6234 Diamond-Blackfan anemia 15 with mandibulofacial dysostosis AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Hematologic; Musculoskeletal; Oncologic Audiologic/Otolaryngologic; Hematologic; Oncologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 11424144; 24942156 RPS29 10419 6235 Diamond-Blackfan anemia 13 AD Pediatric Cardiovascular; Hematologic; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; BMT has been described 24829207 RPS6KA3 10432 6197 Coffin-Lowry syndrome; Mental retardation, X-linked 19 XL Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Neurologic Audiologic/Otolaryngologic; Cardiovascular; Neurologic The condition can include premature death from cardiovascular complications, including cardiomyopathy, and surveillance (including with echocardiogram and electrocardiogram) may allow early medical management ; The condition may include hearing deficits, and surveillance may be beneficial; Medical management of stimulus-induced drop attacks (eg, with valproate, clonazepam, or SSRIs) may be beneficial, as are measures to prevent injuries from related falls 5581017; 5052411; 1133653; 146889; 7681250; 7943043; 9719387; 9832033; 9744638; 10528858; 10319851; 11160957; 12210291; 15214012; 16879200; 17100996; 17318637; 19888300; 20301520; 20637903; 21614984; 22009732; 22490425; 25044551 RPS7 10440 6201 Diamond-Blackfan anemia 8 AD Pediatric Craniofacial; Hematologic; Oncologic Hematologic; Oncologic Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 16317735; 19061985; 20301769; 23718193; 23812780 RPSA 6502 3921 Asplenia, isolated congenital AD Pediatric Allergy/Immunology/Infectious; Gastrointestinal Allergy/Immunology/Infectious Individuals are susceptible to severe bacterial infections in early life, and awareness may allow prophylaxis and early and aggressive management of infections 20846672; 23579497 RRAS2 17271 22800 Noonan syndrome 12 AD Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular Surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis and other congenital heart anomalies) can be beneficial 31130282; 31130285 RRM2B 17296 50484 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 5; Mitochondrial DNA depletion syndrome 8A; Mitochondrial DNA depletion syndrome 8B AD/AR N/A N/A Biochemical; Gastrointestinal; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17486094; 19667227; 19138848; 19664747 RS1 10457 6247 Retinoschisis 1, X-linked, juvenile XL N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9326935; 9618178; 10636740; 10533068; 10922205; 10636421; 15531314; 15937075; 17304551; 17172462; 17296904; 20061330; 25999676 RSPH1 12371 89765 Ciliary dyskinesia, primary, 24 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 20301301; 23993197; 24518672 RSPH3 21054 83861 Ciliary dyskinesia, primary, 32 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 26073779 RSPH4A 21558 345895 Ciliary dyskinesia, primary, 11 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 19200523; 20301301 RSPH9 21057 221421 Ciliary dyskinesia, primary, 12 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 19200523; 20301301 RSPO1 21679 284654 Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and 46,XX sex reversal AR Adult Audiologic/Otolaryngologic; Dermatologic; Endocrine; Genitourinary; Oncologic; Ophthalmologic Genitourinary; Oncologic Surveillance/treatment of gonadal tumors and specific malignancies may improve outcome 17041600; 18085567 RSPO2 28583 340419 Tetraamelia syndrome 2; Humerofemoral hypoplasia with radiotibial ray deficiency AR N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8030673; 18837045; 29769720 RSPO4 16175 343637 Anonychia/hyponychia congenita AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4702713; 17186469; 17041604; 17914448; 18070203; 22300369 RSPRY1 29420 89970 Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26365341 RSRC1 24152 51319 Intellectual development disorder, autosomal recessive 70 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28640246; 29522154 RTEL1 15888 51750 Pulmonary fibrosis and/or bone marrow failure, telomere-related 3; Dyskeratosis congenita, autosomal dominant 4; Dyskeratosis congenita, autosomal recessive 5 AD/AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic; Oncologic; Pulmonary Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary For Dyskeratosis congenita, affected individuals have been described with a number of hematopoietic manifestations, including anemia and thrombocytopenia, and have frequently been reported as suffering from bone marrow failure; Individuals may be at increased risk of oncologic processes, and awareness may allow early detection and treatment; HSCT has been described; For treatment related to pulmonary fibrosis, immunotherapy may be beneficial, though lung transplantation may be indicated in individuals with severe/refractory disease 19461895; 23329068; 23453664; 23591994; 23959892; 25848748 RTN2 10468 6253 Spastic paraplegia 12, autosomal dominant AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10677333; 12427890; 22232211 RTN4IP1 18647 84816 Optic atrophy 10 with or without ataxia, mental retardation, and seizures AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26593267 RTTN 18654 25914 Microcephaly, short stature, and polymicrogyria with or without seizures AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22939636; 26608784 RUBCN 28991 9711 Spinocerebellar ataxia, autosomal recessive 15 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20826435; 23728897 RUNX1 10471 861 Platelet disorder, familial, with associated myeloid malignancy AD Pediatric Hematologic; Oncologic Hematologic; Oncologic Individuals can have thrombocytopenia and bleeding episodes (eg, associated with surgical procedures), and awareness may allow preventive measures as well as prompt treatment; There is a reported increased risk of malignancy (such as acute myelogenous leukemia), and awareness may allow surveillance measures enabling early detection and management, which may be beneficial; BMT has been reported 10508512; 11830488; 18478040; 19357396; 19387465; 20846103; 22571758 RUNX2 10472 860 Cleidocranial dysplasia; Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly AD N/A N/A Craniofacial; Dental; Musculoskeletal General Duplications including the gene have also been reported as resulting in additional skeletal anomalies such as craniosynostosis Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14818746; 2301472; 9182765; 10545612; 11746020; 12424590; 16222673; 15952089; 20301686; 20683987; 21734816; 22023169; 22194205; 23220435; 23290074; 23348268; 23558979; 23659235 RUSC2 23625 9853 Mental retardation, autosomal recessive, 61 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27612186 RXFP2 17318 122042 Cryptorchidism AD N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12217959; 12970298 RXYLT1 13530 10329 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10 AR N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General The condition involves multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23217329 RYR1 10483 6261 Malignant hyperthermia, susceptibility 1; Central core disease; Minicore myopathy with external ophthalmoplegia; Centronuclear myopathy AD/AR Pediatric Cardiovascular; Musculoskeletal; Renal Cardiovascular; Musculoskeletal; Renal; Pharmacogenomic Individuals with RYR1-related conditions may be at risk of malignant hyperthermia Individuals with recessive inheritance have been described; Invididuals are susceptible to malignant hyperthermic crisis (which can affect both skeletal muscle and cardiac function) in a number of situations, including when exposed to specific agents such as certain agents used in anesthesia (eg, halothane) or depolarizing muscle relaxants (eg, succinyl choline), and to treat or prevent acute crises, dantrolene can be effective; Individuals may also suffer from exertional rhabdomyolysis or have attacks triggered by tachycardia or acidosis, and precautions may be beneficial; For Minicore myopathy with external ophthalmoplegia, Centronuclear myopathy, individuals with these conditions may also be at risk of malignant hyperthermia, and appropriate precautions may be beneficial 13396066; 637752; 7362206; 7299413; 6348539; 1774074; 8220423; 8220422; 9199552; 9497245; 10097181; 11113224; 11389482; 11448278; 12112081; 12136074; 12467748; 12719381; 14732627; 16380615; 16163667; 16084090; 17190947; 17376685; 18253926; 17538032; 19303294; 19734047; 19807743; 20301565; 20301325; 20839240 RYR2 10484 6262 Ventricular tachycardia, catecholaminergic polymorphic, 1; Arrhythmogenic right ventricular dysplasia 2; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome AD Pediatric Cardiovascular Cardiovascular Mortality is high in untreated Ventricular tachycardia, catecholaminergic polymorphic, 1, and treatment (eg, beta-blockers without sympathomimetic activity) can be effective to reduce syncope, but ICD placement may be needed; In ARVD2, individuals may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome may involve manifestations such as cardiac arrest and sudden cardiad death, with negative exercise stress testing and adrenaline challenge, and awareness may allow preventive measures and rapid treatment of life-threatening episodes 11157710; 11208676; 11159936; 17875969; 20301310; 19926015; 33536282 S1PR2 3169 9294 Deafness, autosomal recessive 68 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 16703383; 26805784 SACS 10519 26278 Spastic ataxia, Charlevoix-Saguenay type AR N/A N/A Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10655055; 12873855; 14718706; 14718708; 15985586; 18398442; 20876471; 21745802; 21993619; 22209141; 22892508; 27133561 SAG 10521 6295 Retinitis pigmentosa 47; Oguchi disease 1 AR N/A N/A Ophthalmologic General Manifesting heterozygotes have been described; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7670478; 9565049; 21447990; 21494281; 21987685; 22665972 SALL1 10524 6299 Townes-Brocks syndrome 1 AD Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Renal Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Renal The condition may be recognizable due to the presence of a specific pattern of congenital malformations affecting hearing as well as multiple organ systems While frequently recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Surveillance for manifestations affecting other organ systems (eg, cardiac, endocrine, and renal) may allow early intervention, potentially reducing morbidity and mortality 5042490; 9072124; 9425907; 10928856; 11484202; 14755477; 16088922; 8000979; 17431915; 20301618 SALL2 10526 6297 Coloboma, ocular, autosomal recessive AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24412933 SALL4 15924 57167 Duane-radial ray/Okohiro syndrome; IVIC syndrome AD Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic; Renal Audiologic/Otolaryngologic; Renal Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with vesicoureteral reflux, and surveillance and management may be helpful to preserve renal function 843249; 7395922; 12395297; 11826030; 12393809; 12789647; 12843316; 12868480; 15342710; 16086360; 16402211; 16411190; 17256792; 20301547 SAMD12 31750 401474 Epilepsy, familial adult myoclonic, 1 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29939203 SAMD9 1348 54809 Mirage syndrome; Monosomy 7 myelodysplasia and leukemia syndrome 2; Tumoral calcinosis, normophosphatemic, familial AD/AR Pediatric Allergy/Immunology/Infectious; Dental; Dermatologic; Endocrine; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic Allergy/Immunology/Infectious; Endocrine; Hematologic; Musculoskeletal; Oncologic Mirage syndrome can include anemia and thrombocytopenia requiring transfusions; Individuals can have severe and recurrent infections, and awareness may allow preventive measures and early and aggressive treatment of infections; Individuals may have salt-wasting adrenal hypoplasia, and awareness may allow prompt recognition and treatment to manage electrolyte and endocrine sequelae; For individuals with Tumoral calcinosis, surveillance/early treatment of tumoral calcinosis may reduce morbidity; Monosomy 7 myelodysplasia and leukemia syndrome 2 involves germline genetic anomaly as well as associated somatic loss of chromosome 7, and results in increased risk of hematologic malignancy such that awareness may allow early diagnosis and management of disease 3366131; 15133511; 16960814; 18094730; 27182967; 28487541; 30046003; 30322869 SAMD9L 1349 219285 Ataxia-pancytopenia syndrome; Monosomy 7 myelodysplasia and leukemia syndrome 1 AD Pediatric Allergy/Immunology/Infectious; Hematologic; Neurologic; Oncologic Allergy/Immunology/Infectious; Hematologic; Oncologic Ataxia-pancytopenia syndrome can include pancytopenia and related infectious risks, and awareness may allow prophylactic measures and early and aggressive treatment of infections and hematologic issues; Individuals have been descriebd with hematologic malignancies, and awareness may allow surveillance and prompt detection and management; Monosomy 7 myelodysplasia and leukemia syndrome 1 involves germline genetic anomaly as well as associated somatic loss of chromosome 7, and results in increased risk of hematologic malignancy such that awareness may allow early diagnosis and management of disease 283689; 27259050; 30046003; 30322869 SAMHD1 15925 25939 For Aicardi-Goutieres syndrome related to variants in SAMHD1, it has been suggested that individuals should be actively screened for intracranial arteriopathy in order to allow prompt intervention, which may reduce morbidity and mortality AR Pediatric Allelic with Chilblain lupus 2 (AD) Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Neurologic Cardiovascular For Aicardi-Goutieres syndrome related to mutations in SAMHD1, it has been suggested that individuals should be actively screened for intracranial arteriopathy in order to allow prompt intervention, which may reduce morbidity and mortality 19525956; 20301648; 20358604; 20653736; 20842748; 21102625; 21402907; 21204240; 21633013; 22149989 SAR1B 10535 51128 Chylomicron retention disease (Anderson disease) AR Pediatric Gastrointestinal; Musculoskeletal; Neurologic Gastrointestinal Individuals typically present in infancy with with steatorrhea and failure to thrive, and dietary measures (maintenance of adequate caloric intake on a low-long chain fat diet consisting of polyunsaturated fatty acids, with supplementation of lipid soluble vitamins, including large amounts of vitamin E, and essential fatty acids) can be beneficial 2426307; 3792776; 7601203; 10521380; 10665502; 12692552; 17309654; 20920215 SARS1 10537 6301 Neurodevelopmental disorder with microcephaly, ataxia, and seizures AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28236339 SARS2 17697 54938 Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis syndrome AR N/A N/A Endocrine; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21255763 SART3 16860 9733 Porokeratosis, disseminated superficial actinic, 1 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15840095 SASH1 19182 23328 Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma AR Adult Allelic with Dyschromatosis universalis hereditaria 1 (AD) Dental; Dermatologic; Oncologic Oncologic The condition can involve the development of squamous cell carcinomas, and awareness may allow surveilance in order to allow prompt diagnosis and management 25315659; 26203640; 27659786; 27840890; 28407215; 29956681 SASS6 25403 163786 Microcephaly 14, primary, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24951542; 30639237 SATB1 10541 6304 Developmental delay with dysmorphic facies and dental anomalies; Kohlschutter-Tonz syndrome-like AD N/A N/A Cardiovascular; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33513338 SATB2 21637 23314 Glass syndrome AD N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17377962; 19170718; 19668335; 22521361; 23925499; 24301056; 24363063; 25118029 SBDS 19440 51119 Shwachman-Diamond syndrome 1; Aplastic anemia AD/AR Pediatric Allergy/Immunology/Infectious; Gastrointestinal; Hematologic; Musculoskeletal; Oncologic Allergy/Immunology/Infectious; Gastrointestinal; Hematologic; Oncologic Heterozygous variants can result in incompletely penetrant aplastic anemia In Aplastic anemia, surveillance and prompt treatment of aplastic anemia and bone marrow failure, as well as associated myelodysplasia, which has been reported, may reduce morbidity; BMT and HSCT have been reported; In Shwachman-Diamond syndrome, medical treatment (eg, pancreatic enzymes, fat-soluble vitamins) can be effective to treat pancreatic exocrine insufficiency; Blood/platelet transfusions may be necessary; Due to neutropenia and infectious risk, G-CSF and other prophylactic measures (eg antibiotics), as well as early and aggressive treatment of infections, may be beneficial, but prolonged use of agents such as G-CSF may have adverse effects; Regular surveillance for hematologic anomalies is recommended; Awareness of the risk of malignant transformation may allow early detection and management; HSCT use has been reported 14221166; 7264801; 8942739; 8759887; 9359520; 10467990; 10393609; 12183725; 12496757; 14984468; 15769891; 17376717; 17400792; 17478638; 17916435; 20301722; 22554078; 22992231; 23305959; 23351992 SBF1 10542 6305 Charcot-Marie-Tooth disease, type 4B3 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21210780; 23749797; 24799518 SBF2 2135 81846 Charcot-Marie-Tooth disease, type 4B2 with early-onset glaucoma AR Pediatric Audiologic/Otolaryngologic; Neurologic; Ophthalmologic Ophthalmologic; Pharmacogenomic Several families with CMT4B2 with early-onset glaucoma have been reported; One report has also described homozygous variants associated with Congenital thrombocytopenia, autosomal recessive Open-angle glaucoma is typically asymptomatic until late stages, when irreversible nerve damage has already taken place; As the condition may include early-onset hearing loss, intervention related to speech and language development may be beneficial; Agents that may contribute to glaucoma should be avoided 9521281; 10932274; 12687498; 12554688; 15477569; 15304601; 23334996 SC5D 10547 6309 Lathosterolosis AR N/A N/A Biochemical; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies; Lipid storage has been reported as being aggravated by supplemental cholesterol Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12189593; 12812989; 17853487; 19123163 SCAPER 13081 49855 Intellectual developmental disorder and retinitis pigmentosa AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28794130 SCARB2 1665 950 Epilepsy, progressive myoclonic 4, with or without renal failure AR N/A N/A Cardiovascular; Neurologic; Renal General In addition to other manifestations, renal dysfunction and cardiomyopathy have been reported; Renal transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15364701; 17030781; 18424452; 18308289; 19847901; 21782476; 21670406; 22032306; 22050460; 22767442 SCARF2 19869 91179 Van den Ende-Gupta syndrome AR N/A N/A Craniofacial; Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20887961; 23808541; 24478002 SCD5 21088 79966 Deafness, autosomal dominant 79 AD N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31972369 SCN10A 10582 6336 Episodic pain syndrome, familial, 2 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23115331 SCN11A 10583 11280 Episodic pain syndrome, familial, 3; Neuropathy, hereditary sensory and autonomic, type VII AD N/A N/A Neurologic General The pain has been reported as responsive to oral anti-inflammatory analgesics; Congenital insensitivity to pain can result in injuries and infections Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24036948; 24207120; 24776970; 25118027 SCN1A 10585 6323 Migraine, familial hemiplegic 3 AD Pediatric Allelic with Developmental and epileptic encephalopathy 6B (AD); Dravet syndrome (AD); Generalized epilepsy with febrile seizures plus, type 2 (AD) Neurologic Neurologic; Pharmacogenomic For conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Vasoconstricting agents (due to risk of stroke) and cerebral angiography (due to risk of precipitation of attack) should be avoided 10486327; 10852559; 10742094; 11524484; 15277634; 16054936; 16326807; 16505326; 17190949; 17347258; 20301562; 19522081; 19332696; 28331464 SCN1B 10586 6324 Atrial fibrillation, familial 13; Brugada syndrome 5 AD Pediatric Allelic with Epilepsy, generalized, with febrile seizures plus, type 1 (AD); Developmental and epileptic encephalopathy 52 (AR) Cardiovascular; Neurologic Cardiovascular; Pharmacogenomic In Atrial fibrillation, surveillance (eg, with echocardiogram and electrocardiogram) may allow early medical and/or surgical management (eg, atrioventricular nodal ablation followed by dual-chamber pacemaker implantation has been described), which may be beneficial; In Brugada syndrome, surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever 9697698; 12011299; 14504340; 18464934; 19808477; 20301690; 23148524; 28218389 SCN2A 10588 6326 Developmental and epileptic encephalopathy 11; Seizures, benign familial infantile, 3; Episodic ataxia, type 9 AD Pediatric Neurologic Neurologic In Epileptic encephalopathy, early infantile, 11 and Seizures, benign familial infantile, 3, individuals may manifest with seizures (among other findings), and specific knowledge of the underlying cause can help direct selection of optimal therapies for management based on the genetic etiology; In Episodic ataxia, type 9, individuals manifest with ataxic episodes, and treatment with acetazolamide has been reported to be effective in some patients 6660252; 3508699; 8734025; 11326335; 15048894; 15028761; 19786696; 20956790; 22029951; 22591750; 22612257; 23020937; 26645390; 28331464; 30415926; 30643928; 30870728; 30928199; 31487502 SCN2B 10589 6327 Atrial fibrillation, familial 14 AD Adult Cardiovascular Cardiovascular In Atrial fibrillation, surveillance (eg, with echocardiogram and electrocardiogram) may allow early management, which may be beneficial 19808477 SCN3A 10590 6328 Epilepsy, familial focal, with variable foci 4; Developmental and epileptic encephalopathy 62 AD N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24157691; 29466837 SCN3B 20665 55800 Brugada syndrome 7; Atrial fibrillation, familial 16 AD Adult Cardiovascular Cardiovascular; Pharmacogenomic In Atrial fibrilliation, medical/preventive management may decrease morbidity; In Brugada syndrome, surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever 20031595; 20301690; 20558140; 21051419 SCN4A 10591 6329 Paramyotonia congenita; Hyperkalemic periodic paralysis, type 2; Hypokalemic periodic paralysis, type 2; Normokalemic potassium-sensitive periodic paralysis; Malignant hyperthermia, susceptibility to; Myasthenic syndrome, congenital, 16; Myotonia, potassium-aggravated AD/AR Pediatric Cardiovascular; Musculoskeletal; Neurologic Cardiovascular; Musculoskeletal; Neurologic; Pharmacogenomic Clinically, allelic conditions have been divided into different forms of the disorder: paramyotonia, potassium-aggravated myotonia, and periodic paralysis; Potassium-aggravated myotonia includes mild myotonia fluctuans, severe myotonia permanens, and acetazolamide-responsive myotonia In hypokalemic disease, treatment, such as potassium supplementation can be effective; Acetazolamide treatment is beneficial in the majority (including with normokalemic and hyperkalemic disease), but in a lower proportion of variant-negative patients; Individuals can have cardiac complications, including sudden cardiac death; In Paramyotonia congenita, medications (eg, mexilitene, carbamazepine, phenytoin) may be effect in some individuals, and avoidance and specific preciptating circumstances may be beneficial; Myotonia, potassium-aggravated can be aggravated by potassium and fasting, and effectively treated with medications (eg, acetazolamide, carbamazepine, mexilitene); In Malignant hyperthermia, early diagnosis, discontinuation of potent inhalation agents/succinylcholine, treatment of metabolic abnormalities, and administration of dantrolene sodium intravenously are essential to treat acute MH; In Myasthenic syndrome, congenital, pyridostigmine can improve endurance; Acetazolamide can prevent further attacks of respiratory and bulbar weakness 13544644; 13758355; 13963901; 13946346; 14090531; 5828532; 14237771; 673408; 852462; 4022357; 3587272; 2396930; 1654742; 1310898; 1338909; 1316765; 8424309; 8385748; 8242056; 8308722; 8058156; 7741283; 9131651; 9131654; 10599760; 10369308; 10930446; 10727489; 12933953; 12766226; 15534250; 15557532; 15596759; 15642860; 16832098; 16786525; 17998485; 18203179; 19015492; 19015483; 18337100; 19118277; 20237798; 20301512; 20301669; 20713951; 21220685; 22617007; 23460624; 23516313; 23771340; 23801527; 23958773; 24082935; 25707578 SCN4B 10592 6330 Long QT syndrome 10; Atrial fibrilliation, familial 17 AD Pediatric Cardiovascular Cardiovascular In Atrial fibrillation and Long QT syndrome, surveillance and medical and/or surgical management related to arrhythmias may be helpful to help decrease morbidity 17592081; 20301308; 23604097 SCN5A 10593 6331 Atrial fibrillation, familial 10; Long QT syndrome 3; Idiopathic ventricular fibrillation; Heart block, progressive, type IA; Heart block, nonprogressive; Sick sinus syndrome 1, autosomal recessive; Cardiomyopathy, dilated, 1E; Brugada syndrome 1; Ventricular fibrillation, familial 1 AD/AR/Digenic Pediatric Cardiovascular Cardiovascular; Pharmacogenomic The inheriatance of conditions such as LQTS and Atrial standstill may involve digenic inheritance involving other genes, such as GJA5 In Atrial fibrilliation, medical/preventive management may decrease morbidity; In Sick sinus syndrome, in pediatric patients, treatment of associated exercise intolerance, presyncope or syncope, typically requires lifelong cardiac pacing; For dysrhthymia-related phenotypes, surveillance and preventive/treatment measures (eg, in LQTS3: beta-blockers, pacemakers, or ICD; In CMD1E: permanent pacing is required in most individuals; Brugada syndrome: ICDs) can decrease morbidity/mortality; For progressive/nonprogressive heart block, surveillance can allow timely treatment (eg, with pacemaker); Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever 3953067; 8541846; 7889574; 9521325; 10590249; 10471492; 10940383; 10911008; 11748104; 11901046; 11823453; 14523039; 12574143; 12522116; 15466643; 15051636; 15671429; 15840476; 16922724; 16453024; 17038146; 18599870; 18378609; 19122847; 18451998; 18503232; 20025708; 20301690 SCN8A 10596 6334 Developmental and epileptic encephalopathy 13; Seizures, benign familial infantile, 5 AD Pediatric Allelic with Cognitive impairment with or without cerebellar ataxia (AD); Myoclonus, familial 2 (AD) Neurologic; Ophthalmologic Neurologic As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Individuals may manifest with seizures, and specific knowledge of the underlying cause can help direct selection of optimal therapies for management based on the genetic etiology 16236810; 22365152; 24888894; 25239001; 26677014; 27210545; 28331464; 29726066; 31026061; 31402610 SCN9A 10597 6335 Paroxysmal extreme pain disorder AD/AR Pediatric Allelic with Small fiber neuropathy (AD); Erythermalgia, primary (AD); Geberalized epilepsy with febrile seizures plus, type 7 (AD); Indifference to pain, congenital, autosomal recessive (AR) Dermatologic; Neurologic Neurologic Many treatments have been attempted (with inconsistent success) in Erythermalgia, primary, and some have been described by patients as providing subjective relief from symptoms; Indifference to pain, congenital, can result in injuries, some of which may in theory be preventable with early diagnosis and preventive measures In Primary erythermalgia, medical treatment (with specific sodium channel blocking agents such as XEN402) has been reported as beneficial; Individuals with Paroxysmal extreme pain disorder have been reported as responding to medical therapy (eg, carbamazepine) in terms of clinical manifestations (attacks of pain) as well as psychomotor development in some 13636703; 4111621; 4112340; 1536168; 10724194; 14985375; 15958509; 16216943; 17167479; 17145499; 17679678; 17470132; 19304393; 19763161; 21441906; 21698661; 22035805; 23596073; 24817410 SCNN1A 10599 6337 Pseudohypoaldosteronism, type I; Liddle syndrome 3; Bronchiectasis with or without elevated sweat chloride 2 AD/AR/Digenic (with CFTR or other SCCN1 genes) Pediatric Allergy/Immunology/Infectious; Pulmonary; Renal Allergy/Immunology/Infectious; Pulmonary; Renal In Pseudohypoaldosteronism, type I, treatment with electrolyte replacement and control of hyperkalemia can be effective; In Liddle syndrome, certain medications (eg, amiloride, triamterene, but not spironolactone) and dietary sodium restriction can effectively treat hypertension and hypokalemia; In Bronchiectasis with or without elevated sweat chloride 2, as in cystic fibrosis, early and aggressive pulmonary and other management (eg, related to prophylaxis and management of respiratory infections) may decrease morbidity 8589714; 9654209; 10202170; 9462466; 19017867 SCNN1B 10600 6338 Pseudohypoaldosteronism, type I; Liddle syndrome 1; Bronchiectasis with or without elevated sweat chloride 1 AD/AR/Digenic (with CFTR or other SCCN1 genes) Pediatric Allergy/Immunology/Infectious; Pulmonary; Renal Allergy/Immunology/Infectious; Pulmonary; Renal In Pseudohypoaldosteronism, type I, treatment with electrolyte replacement and control of hyperkalemia can be effective; In Liddle syndrome, certain medications (eg, amiloride, triamterene, but not spironolactone) and dietary sodium restriction can effectively treat hypertension and hypokalemia; In Bronchiectasis with or without elevated sweat chloride 1, as in cystic fibrosis, early and aggressive pulmonary and other management (eg, related to prophylaxis and management of respiratory infections) may decrease morbidity 7046191; 6262354; 3550146; 264740; 7954808; 8524790; 8589714; 10202170; 16207733; 18507830; 19017867 SCNN1G 10602 6340 Pseudohypoaldosteronism, type I; Liddle syndrome 2; Bronchiectasis with or without elevated sweat chloride 3 AD/AR/Digenic (with CFTR or other SCCN1 genes) Pediatric Allergy/Immunology/Infectious; Pulmonary; Renal Allergy/Immunology/Infectious; Pulmonary; Renal In Pseudohypoaldosteronism, type I, treatment with electrolyte replacement and control of hyperkalemia can be effective; In Liddle syndrome, certain medications (eg, amiloride, triamterene, but not spironolactone) and dietary sodium restriction can effectively treat hypertension and hypokalemia; In Bronchiectasis with or without elevated sweat chloride 3, as in cystic fibrosis, early and aggressive pulmonary and other management (eg, related to prophylaxis and management of respiratory infections) may decrease morbidity 7046191; 3550146; 3550146; 7550319; 8640238; 9649551; 10202170; 18507830; 19017867 SCO1 10603 6341 Mitochondrial complex IV deficiency, nuclear type 4 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Attention deficit-hyperactivity disorder, susceptibility to refers to a susceptibility locus and/or evidence or clinical applicability unclear 11013136; 22231385 SCO2 10604 9997 Myopia 6; Mitochondrial complex IV deficiency, nuclear type 2 AD/AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10545952; 10749987; 12538779; 15210538; 18924171; 22231385; 23364397; 23643385 SCP2 10606 6342 Leukoencephalopathy with dystonia and motor neuropathy AR N/A N/A Biochemical; Endocrine; Genitourinary; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16685654 SCUBE3 13655 222663 Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dental; Musculoskeletal; Neurologic Cardiovascular Among other features, the condition can involve arrhythmias, and awareness can allow early diagnosis and management 33308444 SCYL1 14372 57410 Spinocerebellar ataxia, autosomal recessive 21 AR Pediatric Gastrointestinal; Neurologic Gastrointestinal Individuals have been described with childhood-onset acute liver failure, and awareness may allow surveillance and prompt management 26581903 SCYL2 19286 55681 Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum AR N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31960134 SDCCAG8 10671 10806 Bardet-Biedl syndrome 16; Senior-Loken syndrome 7 AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic; Renal General Renal transplant has been described; The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20835237; 22626039 SDHA 10680 6389 Paragangliomas 5; Gastrointestinal stromal tumors; Cardiomyopathy, dilated, 1GG; Neurodegeneration with ataxia and late-onset optic atrophy; Mitochondrial respiratory chain complex II deficiency, nuclear type 1 AD/AR Adult (Paragangliomas 5; Gastrointestinal stromal tumors); Pediatric (Cardiomyopathy, dilated, 1GG; Neurodegeneration with ataxia and late-onset optic atrophy; Leigh syndrome/Mitochondrial respiratory chain complex II deficiency) Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Oncologic Biochemical; Cardiovascular; Gastrointestinal; Oncologic For Parangangliomas, symptoms are reported as resolving after surgical tumor resection; For Gastrointestinal stromal tumors, surveillance may allow early diagnosis and treatment, which may improve outcomes; In conditions such as Cardiomyopathy, dilated, Neurodegeneration with ataxia and late-onset optic atrophy; and Mitochondrial respiratory chain complex II deficiency, nuclear type 1, recognition of cardiovascular disease may allow early medical management, which may be helpful to help decrease morbidity; In Mitochondrial respiratory chain complex II deficiency, medical treatment (eg, with riboflavin, ubiquinol) may be beneficial, and individuals may have cardiac involvement such that surveillance may be beneficial 7550341; 8967754; 10746566; 10976639; 12794685; 16737791; 16798039; 20484225; 20551992; 21505157; 22972948; 23322652; 27683074 SDHAF1 33867 644096 Mitochondrial complex II deficiency, nuclear type 2 AR Pediatric N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic Biochemical; Cardiovascular Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may multisystemic, including cardiac, involvemen (which can include arrhythmias), and surveillance and early interventions may be beneficial 12112045; 16737791; 19465911; 22995659; 23322652 SDHAF2 26034 54949 Paragangliomas 2 AD Pediatric Oncologic Oncologic Surveillance/early treatment of tumors (eg, surgical resection) can be effective 6286462; 19628817; 20071235; 21348866; 20301715; 21224366; 22584701; 23061808; 23078982 SDHB 10681 6390 Cowden syndrome 2; Paraganglioma and gastric stromal sarcoma; Gastrointestinal stromal tumor; Pheochromocytoma; Paragangliomas 4; Mitochondrial complex II deficiency, nuclear type 4 AD/AR Pediatric Biochemical; Cardiovascular; Neurologic; Oncologic Biochemical; Cardiovascular; Oncologic The proof for causation related to Cowden syndrome is unclear In conditions related to neoplasms, surveillance for and early diagnosis/treatment of associated neoplasms can be beneficial; In Mitochondrial complex II deficiency, nuclear type 4, medical management (eg, with riboflavin and coenzyme Q10) has been described, and individuals may have cardiac involvement such that surveillance may be beneficial 490809; 11404820; 12000816; 12213855; 12364472; 14500403; 15479192; 15328326; 14685938; 16317055; 17102084; 16522703; 17652212; 17848412; 17804857; 17200167; 18057081; 17667967; 18678321; 19251979; 19351833; 19576851; 20301715; 20503330; 21366490; 21565294; 21348866; 22328163; 22972948; 23322652; 26925370; 27604842; 32124427 SDHC 10682 6391 Paraganglioma and gastric stromal sarcoma; Gastrointestinal stromal tumor; Paragangliomas 3 AD Pediatric Oncologic Oncologic Surveillance/early treatment of neoplasms may improve outcomes 15342702; 15342702; 16249420; 17804857; 17667967; 21173220; 21348866; 22703879 SDHD 10683 6392 Cowden syndrome 3; Paraganglioma and gastric stromal sarcoma; Pheochromocytoma; Paragangliomas 1; Carcinoid tumors, intestinal; Mitochondrial complex II deficiency, nuclear type 3 AD/AR Pediatric Allelic with Mitochondrial complex II deficiency, nuclear type 3 (AR) Biochemical; Cardiovascular; Neurologic; Oncologic Biochemical; Cardiovascular; Oncologic In conditions related to neoplasms, surveillance for and early diagnosis/treatment of associated neoplasms can be beneficial; In Mitochondrial respiratory chain complex II deficiency, medical treatment (eg, with riboflavin, ubiquinol) may be beneficial, and individuals may have cardiac involvement such that surveillance may be beneficial 10657297; 11156372; 11526495; 11343322; 11519521; 12000816; 12205103; 12111639; 12007193; 12811540; 15032977; 15479192; 15328326; 16317055; 17848412; 17804857; 17667967; 18678321; 19239085; 19584903; 21348866; 21565294; 22261759; 22948026; 23072324; 23099648; 23322652; 24367056; 26008905 SDR9C7 29958 121214 Ichthyosis, congenital, autosomal recessive 13 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28173123 SEC23A 10701 10484 Craniolenticulosutural dysplasia AR N/A N/A Craniofacial; Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12677423; 16980979; 21039434 SEC23B 10702 10483 Cowden syndrome 7; Anemia, dyserythropoietic congenital, type II AD/AR Pediatric (Anemia, dyserythropoietic congenital, type II); Adult (Cowden syndrome 7) Endocrine; Gastrointestinal; Hematologic; Oncologic Gastrointestinal; Hematologic; Oncologic Heterozygotes with variants related to Anemia, dyserythropoietic congenital, type II may have mild manifestations Individuals with Cowden syndrome have been described with cancer, and awareness may be beneficial to allow screening, prompt diagnosis, and management; Individuals with Anemia, dyserythropoietic congenital, type II may require RBC transfusions in the neonatal period; Splenectomy may be beneficial; Gallbladder complications are common, and early treatment may be beneficial; Iron overload is common 13884336; 5807784; 5807786; 4340898; 10753261; 11493480; 19621418; 19561605; 20381388; 20941788;21252497; 21378561; 21850656; 22208203; 22428539; 23065504; 23453696; 23940284; 23978024; 24196372; 26522472 SEC24D 10706 9871 Cole-Carpenter syndrome 2 AR N/A N/A Craniofacial; Dental; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25683121; 26467156; 27942778; 30462379 SEC31A 17052 22872 Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies AR N/A N/A Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30464055 SEC61A1 18276 29927 Tubulointerstitial kidney disease, autosomal dominant, 5 AD Pediatric Renal Renal Individuals may have anemia, and medical management (with erythropoietin) has been described as beneficial; The hyperuricemic nephropathy may manifest with a number of variable renal sequelae, and early awareness may allow prompt medical management 27392076 SEC63 21082 11231 Polycystic liver disease 2 with or without kidney cysts AD N/A N/A Gastrointestinal General Though some individuals may require treatment, it is unclear if early (genetic) diagnosis would be beneficial; Liver transplantion has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15133510; 22099398; 23209713 SECISBP2 30972 79048 Selenoprotein deficiency; Thyroid hormone metabolism, abnormal AR N/A N/A Audiologic/Otolaryngologic; Endocrine; Musculoskeletal; Neurologic General Findings, such as growth retardation, may be transient, and the overall phenotypic range has been described as wide Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16228000; 19265499; 19602558; 19769464; 20501692; 20685891; 21084748; 21511232; 22247018; 22986150; 29882503 SELENBP1 10719 8991 Extraoral halitosis due to MTO deficiency AR N/A N/A Biochemical General The clinical relevance is unclear 29255262 SELENOI 29361 85465 Spastic paraplegia 81, autosomal recessive AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28052917; 29500230 SELENON 15999 57190 Rigid spine muscular dystrophy 1; Myopathy, congenital, with fiber-type disproportion AR N/A N/A Musculoskeletal General Cardiac involvement has been described in some individuals Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7224095; 11528383; 12192640; 15122708; 16365872; 20301436; 20301467; 21670436 SEMA3A 10723 10371 Hypogonadotropic hypogonadism 16 with or without anosmia AD Pediatric Endocrine; Genitourinary; Neurologic Endocrine Surveillance in adolescence related to sexual maturation is indicated, and in order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required Surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 22416012 SEMA3E 10727 9723 CHARGE syndrome AD N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11241468; 15235037 SEMA4A 10729 64218 Cone-rod dystrophy 10; Retinitis pigmentosa 35 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16199541 SEMA6B 10739 10501 Epilepsy, progressive myoclonic, 11 AD N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32169168 SEMA7A 10741 8482 Blood group, John Milton Hagen AD Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 17207242; 20854351 SEPSECS 30605 51091 Pontocerebellar hypoplasia, type 2D AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12920088; 20920667; 25044680 SEPTIN12 26348 124404 Spermatogenic failure 10 AD N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22275165; 22479503 SEPTIN9 7323 10801 Amyotrophy, hereditary neuralgic AD N/A N/A Craniofacial; Neurologic Neurologic It has been reported that medical treatment (eg, with corticosteroids) may prevent attacks of brachial plexus neuropathy during specific situations, such as during surgery and in childbirth 11739810; 16186812; 18492087; 19451530; 19939853; 20301569; 23042485 SERAC1 21061 84947 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16527507; 22683713; 23707711 SERPINA1 8941 5265 Alpha-1-Antitrypsin deficiency AR Pediatric Gastrointestinal; Pulmonary Gastrointestinal; Pulmonary Medical treatment (augmentation therapy with purified alpha-1-antitrypsin, Vitamin E supplementation) can be helpful for pulmonary and hepatic manifestations; Exacerbating factors (eg, smoking) should be avoided; Liver transplantation may be necessary in individuals with severe liver manifestations 4240153; 4117022; 3494198; 2185272; 2035327; 7875269; 8066566; 10898319; 12740257; 11320399; 12452881; 12574076; 14522813; 15282394; 15214923; 20301692; 21457231; 21752289; 22016686; 22215832; 22330941; 22500781; 22536580; 22933512; 23055718; 23251618; 23766346 SERPINA6 1540 866 Corticosteroid-binding globulin deficiency AD/AR N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7061486; 8212073; 10634411; 11502797; 17245537; 20610591; 22013108; 22337907; 22948765 SERPINA7 11583 6906 Thyroxine-binding globulin deficiency; Thyroxine-binding globulin excess XL N/A N/A Endocrine General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8530630; 11600582; 11889160; 19415532 SERPINB6 8950 5269 Deafness, autosomal recessive 91 AR N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20451170; 24963352 SERPINB7 13902 8710 Palmoplantar keratoderma, Nagashima type AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24207119; 24773080 SERPINB8 8952 5271 Peeling skin syndrome 5 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27476651 SERPINC1 775 462 Antithrombin III deficiency AD/AR Pediatric Hematologic Hematologic The inheritance depends on specific variant Individuals may be at high risk for thromboembolism, and recognition may allow preventive/prophylactic measures as well as prompt treatment of thromboembolic and related manifestations, including medical treatment with antithrombin, and chronic anticoagulations, which is indicated in asymptomatic individuals as well as those who have previously suffered sequelae 14347873; 6582486; 3055413; 3350974; 1868237; 2146503; 1671110; 8091378; 16705712; 18208532; 19760264; 21655678; 21655682; 21240680; 21325262; 22997155; 22961244 SERPIND1 4838 3053 Heparin cofactor II deficiency AD N/A N/A Hematologic General Individuals may be at higher risk for thrombophilia, though data are controversial, and may be clinically relevant only in the presence of another thrombophilia-related variant Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2863444; 3603411; 2647747; 1615493; 8902986; 8562924; 9607121; 10650845; 10494755; 12421148; 15337701 SERPINE1 8583 5054 Plasminogen activator inhibitor-1 deficiency AR Pediatric Hematologic Hematologic Individuals are susceptible to bleeding related to situations such as traumatic injury or surgery, and females manifest with menorrhagia, and precautions may be helpful to avoid severe sequelae; Medical treatment (eg, with fibrinolysis inhibitors) have been reported as beneficial in the prevention and treatment of bleeding episodes 2496147; 1435917; 9207454; 10754381; 15650551; 20664190; 21486382 SERPINF1 8824 5176 Osteogenesis imperfecta, type VI AR N/A N/A Musculoskeletal General Bisphosphonates may reduce fracture frequency, and use of RANKL antibody has been described as potentially beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11771667; 17127117; 21353196; 21826736; 22947550; 23613367 SERPINF2 9075 5345 Alpha-2-plasmin inhibitor deficiency AD/AR Pediatric Hematologic Hematologic Anti-fibrinolytic agents or FFP can be used to treat bleeding episodes, and to and prevent patients hemorrhagic complications in those who are undergoing surgical interventions; Intramedullary hematoma is also a common feature, and awareness of this potential manifestation can be beneficial in order to institute efficient treatment; Heterozygotes may also have (milder) manifestations 82839; 156196; 89324; 7095605; 2496145; 2572590; 1806461; 9880645; 10583218; 11472338; 19141165; 19593116; 21873355 SERPING1 1228 710 Angioedema, hereditary, types I and II AD/AR Pediatric Allelic with Complement component 4, partial deficiency of (AD) Allergy/Immunology/Infectious; Gastrointestinal Allergy/Immunology/Infectious Medical treatment (eg, with C1 inhibitor concentrate, ecallantide, icatabant) may be beneficial to prevent and/or treat acute attacks 4393526; 4551861; 792688; 7091182; 3587308; 3653633; 3056508; 3693762; 2723063; 2365061; 2296585; 1885769; 1684567; 1339401; 1459574; 8396558; 8330878; 7618673; 7883978; 8755917; 8628358; 11700154; 11743247; 15971231; 16470590; 16813612 ; 17137866; 17502473; 19752569; 20695852; 20818887; 20818888; 20818886; 21208117; 21864911; 22748405; 22800873; 22831796; 22882460; 23123409; 23437219; 23583915; 23607500; 23678554; 23689237 SERPINH1 1546 871 Osteogenesis imperfecta, type X AR N/A N/A Craniofacial; Dental; Musculoskeletal; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20188343 SERPINI1 8943 5274 Encephalopathy, familial, with neuroserpin inclusion bodies AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10517635; 12103288 SET 10760 6418 Mental retardation, autosomal dominant, 58 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28135719; 28135719; 29688601 SETBP1 15573 26040 Mental retardation, autosomal dominant 29; Schinzel-Giedion midface retraction syndrome AD N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Renal General The condition can involve neoplasms (neuroepithelial neoplasia), as well as multiple congenital malformations affecting a number of organ systems Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 665725; 7506484; 7864048; 8849020; 9738870; 18398855; 20436468; 21371013; 22333924; 23400866; 25217958 SETD1A 29010 9739 Epilepsy, early-onset, with or without developmental delay; Neurodevelopmental disorder with speech impairment and dysmorphic facies AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29463886; 26974950; 31197650; 32346159 SETD1B 29187 23067 Intellectual developmental disorder with seizures and language delay AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29322246; 31110234; 32546566 SETD2 18420 29072 Luscan-Lumish syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22495309; 23160955; 24852293; 25363768; 26084711 SETD5 25566 55209 Mental retardation, autosomal dominant 23 AD N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24680889 SETX 445 23064 Spinocerebellar ataxia, autosomal recessive 1; Amyotrophic lateral sclerosis 4, juvenile; Ataxia with oculomotor apraxia, type 2 AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7214250; 15106121; 14770181; 15732101; 16717225; 16644229; 17096168; 18405395; 18663494; 19141356; 19569000; 19593598; 19696032; 19727998; 19893583; 21438761; 22088787; 22341623; 22577233; 23111195 SF3B4 10771 10262 Acrofacial dysostosis 1, Nager type AD N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22541558; 23568615 SFRP4 10778 6424 Pyle disease AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27355534 SFTPA2 10799 729238 Pulmonary fibrosis, idiopathic AD Pediatric Oncologic; Pulmonary Oncologic Surveillance for and early diagnosis of neoplasms could allow potentially be beneficial treatment 19100526 SFTPB 10801 6439 Surfactant metabolism dysfunction, pulmonary 1 AR Pediatric Pulmonary Pulmonary Lung transplant has been reported as effective in individuals with surfactant B deficiency, and without transplant, the disorder is typically fatal 8421459; 1341413; 8021783; 8071741; 8163685; 7491219; 7647155; 9086529; 9042125; 9506635; 10571948; 10378403; 10365365; 9927351; 11041444; 10960490; 11063734; 10712351; 10663288; 11282516; 11341756; 12784301; 17011330; 17391469; 17109726; 18558554; 19647838; 19220077; 22884059; 23625987 SFTPC 10802 6440 Surfactant metabolism dysfunction, pulmonary, 2 AD Pediatric Pulmonary Pulmonary There have been reports of individuals who received benefit from medical treatment, including hydroxychloroquine, whole-lung lavage, systemic corticosteroids, azathioprine; Lung transplantation may be indicated in individuals with severe and/or refractory disease 11207353; 11445799; 11893657; 11991887; 15039969; 15293602; 15647591; 19443464 SFXN4 16088 119559 Combined oxidative phosphorylation deficiency 18 AR N/A N/A Biochemical; Hematologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24119684 SGCA 10805 6442 Muscular dystrophy, limb-girdle, autosomal recessive 3 AR Pediatric Cardiovascular; Musculoskeletal Cardiovascular The condition can include severe cardiac manifestations, and knowledge may allow surveillance (eg, with EKG, echocardiogram, and Holter monitoring) and early medical management, which may ameliorate morbidity and mortality; Heart transplantation may be indicated in individuals with severe dilated cardiomyopathy 8069911; 7987694; 8528203; 7663524; 9032047; 18285821; 20627570 SGCB 10806 6443 Muscular dystrophy, limb-girdle, autosomal recessive, 4 AR Pediatric Cardiovascular; Musculoskeletal Cardiovascular Digenic inheritance (with SGCD) has been suggested, but the evidence is unclear The condition can include severe cardiac manifestations, including lethal ventricular arrhythmias and dilated cardiomyopathy and knowledge may allow surveillance (eg, with EKG, echocardiogram, and Holter monitoring) and early medical management, which may ameliorate morbidity and mortality; Heart transplantation may be indicated in individuals with severe dilated cardiomyopathy 7581448; 8968749; 7581449; 18285821; 20627570 SGCD 10807 6444 8841194; 8776597; 10735275; 9832045; 10069710; 10974018; 18285821; 19259135 AR Pediatric Cardiovascular; Musculoskeletal Cardiovascular Digenic inheritance (with SGCB) has been suggested, but the evidence is unclear The condition can include severe cardiac manifestations, and knowledge may allow surveillance (eg, with EKG, echocardiogram, and Holter monitoring) and early medical management, which may ameliorate morbidity and mortality; Heart transplantation may be indicated in individuals with severe dilated cardiomyopathy 8841194; 8776597; 10735275; 9832045; 10069710; 10974018,; 18285821; 19259135 SGCE 10808 8910 Dystonia 11, myoclonic AD Pediatric Musculoskeletal; Neurologic Neurologic Treatment with deep-brain stimulation may be beneficial 4434166; 11528394; 12325078; 12391346; 11912106; 12634861; 12821748; 12743249; 16240355; 15728306; 17101905; 16534121; 16227522; 18362280; 20301587; 20800530; 21220679; 21267590; 21825253; 22026499 SGCG 10809 6445 Muscular dystrophy, limb-girdle, limb-girdle, autosomal recessive, 5 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1303286; 7481775; 8923014; 8968757; 10507732; 10720277; 16832103; 18285821 SGMS2 28395 166929 Calvarial doughnut lesions with bone fragility and spondylometaphyseal dysplasia AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30779713 SGPL1 10817 8879 Nephrotic syndrome 14 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Endocrine; Genitourinary; Neurologic; Renal Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Endocrine Individuals have been described with immunodeficiency, including recurrent bacterial infections, and awareness may allow preventative measures and early and aggressive treatment of infections; Individuals have been described with hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with adrenal insufficiency, and awareness may allow early diagnosis and management 28165339; 28165343; 28181337 SGSH 10818 6448 Mucopolysaccharidosis type IIIA (Sanfilippo syndrome A) AR N/A N/A Biochemical; Neurologic General BMT has been described, but was not reported to have a beneficial effect on prognosis Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4252428; 6796310; 7856659; 7493035; 9158154; 9401012; 9554748; 9727849; 9950362; 10518291; 10727844; 11668611; 12000360; 12702166; 15637719; 21061399; 28595941 SH2D1A 10820 4068 Lymphoproliferative syndrome, X-linked, 1 XL Pediatric Allergy/Immunology/Infectious; Hematologic; Oncologic Allergy/Immunology/Infectious; Hematologic; Oncologic Surveillance for EBV infections is indicated; Prompt recognition and treatment of hemophagocytic lymphohistiocytosis (with immunosuppressive agents or rituximab in the case of EBV infection); Treatment for individuals with hypogammaglobulinemia (with IVIG) may be beneficial; Awareness of the increased risk of lymphoma may allow prompt recognition and treatment; HSCT has been described, and is indicated in many individuals 4852784; 48119; 7188959; 6283885; 1847089; 8559596; 9771704; 11133747; 17620557; 20926771; 21971331 SH3BP2 10825 6452 Cherubism AD N/A N/A Craniofacial; Musculoskeletal General As bone lesions are typically self-limiting, surgical interventions treatment may not be necessary (with the exception of aggressive lesions resulting in severe functional issues, or for aesthetic reasons) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11381256; 17368082; 18596838; 19017279; 20301316; 21045962; 22153076; 22640988; 22640403; 22795151 SH3KBP1 13867 30011 Immunodeficiency 61 XL Pediatric Allergy/Immunology/Infectious; Neurologic Allergy/Immunology/Infectious The condition has been described as including early-onset, severe infections, and awareness may allow preventative measures and early and aggressive treatment of infections 29636373 SH3PXD2B 29242 285590 Frank-ter Haar syndrome AR Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular; Ophthalmologic; Pharmacogenomic The condition can include multiple congenital anomalies The condition may be clinically recognizable, but can include macrocornea with or without glaucoma, and surveillance and prompt treatment may be beneficial; Awareness of cardiac anomalies may allow prompt management; Agents that may contribute to glaucoma should be avoided 4805907; 7158646; 9375925; 9188664; 15523657; 20137777; 24105366 SH3TC2 29427 79628 Charcot-Marie-Tooth disease, type 4C; Mononeuropathy of the median nerve, mild AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14574644; 16326826; 16924012; 19744956; 20220177; 20301514; 20301641; 21291453; 22950825 SHANK2 14295 22941 Autism, susceptibility to 17 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20473310 SHANK3 14294 85358 Phelan-McDermid syndrome; Schizophrenia 15 AD N/A N/A Craniofacial; Neurologic General There is evidence that variants in this gene are also involved in autism-related disorders; Deletions have been described as responsible for features of Chromosome 22q13.3 deletion syndrome There is evidence that variants in this gene are also involved in autism-related disorders; Deletions have been described as responsible for feaures of Chromosome 22q13.3 deletion syndrome; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12920066; 17173049; 17999366; 12920066; 20301377; 20385823; 21150887; 21376300; 21606927; 22892527; 22922660 SHH 10848 6469 Holoprosencephaly 3; Microphthalmia with coloboma 5 AD N/A N/A Craniofacial; Endocrine; Neurologic; Ophthalmologic General Variants in SHH have also been implicated in schizencephaly, but the data are unclear, and this may have co-occurred with typical holoprosencephaly-type malformations; Individuals with holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8896572; 10556296; 11471164; 11479728; 12567406; 12503095; 15221788; 19603532; 20531442; 21940735; 1976454; 20104608; 20301702; 22791840; 23112757 SHMT2 10852 6472 Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities AR Pediatric Cardiovascular; Musculoskeletal; Neurologic Cardiovascular Among other findings, the condition can include progressive cardiomyopathy, and awareness may allow early diagnosis and management; Cardiac transplant has been described 33015733 SHOC2 15454 8036 Noonan-like syndrome with loose anagen hair 1 AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Endocrine; Hematologic; Musculoskeletal; Neurologic Cardiovascular; Endocrine; Hematologic Surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis and hypertrophic cardiomyopathy) can be beneficial; Recognition of endocrine anomalies (eg, GH deficiency) may allow early diagnosis and treatment; Individuals with coagulopathy have been reported, and awareness may allow prompt recognition and management 1884862; 9301585; 12673660; 19684605 SHOX 10853 6473 Langer mesomelic dysplasia; Leri-Weill dyschondrosteosis; Short stature, idiopathic familial XL/PAR N/A N/A Musculoskeletal General GH treatment can be effective in idiopathic short stature; Deletion of regulatory elements can also produce manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14344358; 5410085; 6059604; 7365762; 9140395; 9590292; 9590293; 11030412; 11186941; 10713888; 11403039; 11739418; 11932348; 14557470; 12784295; 15173249; 15173321; 15214013; 16227037; 17935511; 17047016; 17200153; 19578035; 19636220; 20301394; 20412871; 20538086; 20683993; 21712857; 21912078; 22020182; 22071895; 22461651; 22518848; 22572840 SHPK 1492 23729 Sedoheptulokinase deficiency AR N/A N/A Biochemical General The clinical relevance is unclear 25647543 SHROOM4 29215 57477 Stocco dos Santos X-linked mental retardation syndrome XL N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2063914; 12673656; 16249884 SI 10856 6476 Sucrase-isomaltase deficiency, congenital AR Pediatric Gastrointestinal Gastrointestinal Sucrose and other carbohydrate ingestion results in osmotic diarrhea, and dietary/medical therapy (eg, sucrose-reduced diet, treatment with sacrosidase) can be effective 5848222; 6082247; 925457; 3553946; 3807985; 3403721; 1717481; 8648532; 8609217; 8648527; 9932843; 10445568; 10903344; 11340066; 12014995; 14724820; 16329100; 18043509; 19680155; 23103650; 23103652; 23103658 SIAH1 10857 6477 Buratti-Harel syndrome AD N/A N/A Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28600779; 32430360 SIGMAR1 8157 10280 Amyotrophic lateral sclerosis 16, juvenile; Frontotemporal lobar degeneration-motor neuron disease; Spinal muscular atrophy, distal, autosomal recessive, 2 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18755042; 21031579; 21842496; 26078401 SIK1 11142 150094 Developmental and epileptic encephalopathy 30 AD N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25839329 SIK3 29165 23387 Spondyloepimetaphyseal dysplasia, Krakow type AR Pediatric Allergy/Immunology/Infectious; Endocrine; Musculoskeletal; Neurologic Allergy/Immunology/Infectious The condition can include immunodeficiency, and awareness may allow antiinfectious prophylaxis and early and aggressive treatment of infection 30232230 SIL1 24624 64374 Marinesco-Sjogren syndrome AR N/A N/A Endocrine; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13053231; 830450; 3683758; 10665502; 14512967; 16282978; 16282977; 17309654; 18285827; 20301371; 20111056; 22219183; 23062754 SIN3A 19353 25942 Witteveen-Kolk syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27399968 SIPA1L3 23801 23094 Cataract 45 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25804400 SIX1 10887 6495 Deafness, autosomal dominant 23; Branchiootorenal syndrome 3; Branchiootic syndrome 3 AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Renal Audiologic/Otolaryngologic; Renal Individuals can have characteristic aural anomalies, but these may not be readily ascertained Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In BOR, surveillance and treatment/prophylaxis related to vesicoureteral reflux can be beneficial 10777717; 15141091; 16652090; 17637804; 18330911; 20301554 SIX3 10889 6496 Holoprosencephaly 2 AD N/A N/A Craniofacial; Endocrine; Neurologic; Ophthalmologic General Variants in SIX3 have also been implicated in schizencephaly, but the data are unclear, and this may have co-occurred with typical holoprosencephaly-type malformations; Individuals with holoprosencephaly may demonstrate endocrine anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10369266; 15221788; 16199538; 17001667; 19346217; 19353631; 20157829; 20531442; 21940735; 21976454; 23112757 SIX5 10891 147912 Branchiootorenal syndrome 2 AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Renal Audiologic/Otolaryngologic; Renal Individuals can have characteristic aural anomalies, but these may not be readily ascertained Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In BOR, surveillance and treatment/prophylaxis related to vesicoureteral reflux can be beneficial 17357085; 20301554 SIX6 10892 4990 Microphthalmia, isolated, with cataract 2; Optic disc anomalies with retinal and/or macular dystrophy AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15266624; 23167593; 24702266 SKI 10896 6497 Shprintzen-Goldberg syndrome AD Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic Cardiovascular Individuals have been described with a number of cardiovascular anomalies, including aortic root dilatation, and spontaneous rupture of arterial aneurysms, and surveillance (eg, including echocardiogram) may allow early management, decreasing morbidity and mortality 23023332 SKIV2L 10898 6499 Trichohepatoenteric syndrome 2 AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal Allergy/Immunology/Infectious; Gastrointestinal Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial; Parenteral nutrition may be required 18982349; 22444670; 23679950 SLC10A2 10906 6555 Bile acid malabsorption, primary AD Pediatric Gastrointestinal Gastrointestinal Individuals may present with manifestations of diarrhea/steatorrhea such as anasarca and nutritional deficiencies due to fecal loss, and dietary and medical interventions (eg, medium chain triglycerides, bile acid sequestrants) may be beneficial 1017717; 430290; 7106511; 9109432; 9109422; 19823678; 21649730 SLC10A7 23088 84068 Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis AR N/A N/A Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29878199; 30082715 SLC11A2 10908 4891 Anemia, hypochromic microcytic, with iron overload AR Pediatric Hematologic Hematologic Individuals can require RBC transfusions and erythropoietin treatment; As hepatic iron overload is common, awareness may allow monitoring and adjustment of treatments and surveillance accordingly 14135503; 15459009; 16439678; 16160008; 16584902; 21871825; 22313374 SLC12A1 10910 6557 Bartter syndrome, antenatal, type 1 AR Pediatric Renal Renal Sequelae can be lethal; Medical treatment of manifestations including hypokalemia and metabolic alkalosis (eg, with KCl supplementation, NSAIDs), as well as related findings such as nephrocalcinosis, can be beneficial 3863906; 8457138; 3888887; 8640224; 9355073; 19513753; 20219833 SLC12A2 10911 6558 Deafness, autosomal dominant 78; Delpire-McNeill syndrome; Kilquist syndrome AD/AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The conditions can include early-onset hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Kilquist syndrome, antiinfectious prophylaxis and early and aggressive treatment of infections, as well as aggressive pulmonary care, may be beneficial 30740830; 32658972; 32754646 SLC12A3 10912 6559 Gitelman syndrome AR Pediatric Cardiovascular; Renal Cardiovascular; Renal Individuals have been reported with cardiovascular manifestations Surveillance for, treatment of, and prevention of electrolyte abnormalities may be beneficial; Individuals with cardiovascular manifestations (eg, arrhythmias such as QTc prolongation) that may warrant interventions have also been described 5929460; 1436349; 81436349; 16120871; 17000984; 17981812; 22009145 SLC12A5 13818 57468 Developmental and epileptic encephalopathy 34 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26333769 SLC12A6 10914 9990 Agenesis of the corpus callosum with peripheral neuropathy (Andermann syndrome) AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14397896; 6329500; 12368912; 12838516; 16606917; 17893295; 20020398; 20301546 SLC13A3 14430 64849 Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30635937 SLC13A5 23089 284111 Developmental and epileptic encephalopathy 25, with ameliogenesis imperfecta AR N/A N/A Dental; Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24995870; 26384929; 27600704; 27913086 SLC14A1 10918 6563 Blood group, Kidd BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion); Jk deficiency may be associated with a urine concentration defect 1498276; 9215669; 11807016 SLC16A1 10922 6566 Hyperinsulinemic hypoglycemia, familial, 7; Erythrocyte lactate transporter defect; Monocarboxylate transporter 1 deficiency AD/AR Pediatric (Erythrocyte lactate transporter defect; Monocarboxylate transporter 1 deficiency ); Adult (Hyperinsulinemic hypoglycemia, familial, 7) Allelic with Myoclonic-atonic epilepsy (AD) Biochemical; Endocrine; Musculoskeletal; Neurologic; Renal Biochemical; Endocrine; Musculoskeletal; Renal Depending on the allelic condition, manifestations in dominant conditions may involve primarily endocrine or musculoskeletal/renal manifestations In Hyperinsulinemic hypoglycemia, familial, several affected individuals have reported as manifesting with severe sequelae, such as hypoglycemia-induced seizures, which could potentially be averted by early recognition and treatment; In Erythrocyte lactate transporter defect, exercise and heat exposure may result in sequelae such as rhabdomyolysis, and precautions may be beneficial; In Monocarboxylate transporter 1 deficiency, ensuring adequate caloric intake has been reported as beneficial to decrease the frequency of episodes of ketoacidotic episodes, and medical management (eg, with intravenous glucose or dextrose and bicarbonate) of episodes has been described as effective in terms of immediate management, and related long-term sequelae 3775384; 3395513; 3395514; 1358043; 10590411; 11207177; 12502513; 17701893; 25390740; 25865495 SLC16A12 23094 387700 Cataract 47 AD N/A N/A Biochemical; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17458810; 18304496 SLC16A2 10923 6567 Allan-Herndon-Dudley syndrome XL Pediatric Craniofacial; Endocrine; Musculoskeletal; Neurologic Endocrine; Obstetric In affected males, treatment with thyroid hormone has not been described as affecting the neurologic phenotype, but heterozygous women may benefit from monitoring and levothyroxine treatment during pregnancy in order to prevent fetal/neonatal hypothyroidism (regardless of fetal variant status) 8484404; 15488219; 14661163; 15889350; 15980113; 18398436; 19194886; 20301789; 20713192; 21098685; 21415082; 21468521 SLC17A5 10933 26503 Infantile sialic acid storage disorder; Sialuria, Finnish type (Salla disease) AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4043964; 10546100; 10069709; 10581036; 10947946; 12121352; 12794687; 12794688; 15172005; 16170568; 19557856; 20101035; 20301643; 20637281 SLC17A8 20151 246213 Deafness, autosomal dominant 25 AD N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11115382; 18674745 SLC17A9 16192 63910 Porokeratosis 8, disseminated superficial actinic type AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25180256 SLC18A2 10935 6571 Parkinsonism-dystonia, infantile, 2 AR Pediatric Neurologic Neurologic The condition can manifest with neurologic manifestations such as movement disorders and autonomic dysfunctiontreatment, and medical management with a dopamine receptor agonist has been described as resulting in marked clinical improvement 23363473 SLC18A3 10936 6572 Myasthenic syndrome, congenital, 21, presynaptic AR Pediatric Musculoskeletal Musculoskeletal Early diagnosis and management has been described as beneficial, as individuals have been reported as responding to medical management (with pyridostigmine) 27590285 SLC19A1 10937 6573 Megaloblastic anemia, folate-responsive AR Pediatric Biochemical; Hematologic Biochemical The condition can manifest with anemia, and managemement (with oral folate) has been reported as being beneficial 32276275 SLC19A2 10938 10560 Thiamine-responsive megaloblastic anemia syndrome AR Pediatric Audiologic/Otolaryngologic; Endocrine; Hematologic Endocrine; Hematologic High-dose thiamine can improve anemia and may ameliorate diabetes; Individuals may also have sensorineural hearing loss, but prelingual onset appears to have not been reported 5767338; 671156; 6175336; 2540004; 1326679; 7707690; 10391221; 10391223; 10074490; 10978358; 19643445; 20301459; 22369132; 22576805; 22876572 SLC19A3 16266 80704 Thiamine metabolism dysfunction syndrome 2 (biotin or thiamine responsive) AR Pediatric Biochemical; Neurologic Biochemical Medical management (with biotin and/or thiamine) has been reported as beneficial; During crises, medical management with biotin and/or thiamine has been reported as resulting in marked improvement within days, and untreated encephalopathies can result in permanent dystonia 9679779; 15871139; 19387023; 20065143; 21176162; 22777947; 23423671; 24878501; 24957181 SLC1A1 10939 6505 Dicarboxylic aminoaciduria AR Adult Allelic with Schizophrenia 18 (AD) Neurologic; Renal Renal Individuals are at high risk of nephrolithiasis, and awareness may allow preventive measures and early management 21123949; 23341099 SLC1A2 10940 6506 Developmental and epileptic encephalopathy 41 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23934111; 27476654 SLC1A3 10941 6507 Episodic ataxia, type 6 AD Pediatric Neurologic Neurologic Invididuals present with attacks of episodic ataxia, which may be severe in some individuals, and treatment with acetazolamide has been reported as being effective 16116111; 19139306 SLC1A4 10942 6509 Spastic tetraplegia, thin corpus callosum, and progressive microcephaly AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25930971; 26041762; 26138499; 29989513; 31763347 SLC20A2 10947 6575 Basal ganglia calcification, idiopathic, 1 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20552677; 22327515; 24463626 SLC22A12 17989 116085 Hypouricemia, renal 1 AR Pediatric Renal Renal The condition may be asymptomatic, but a minority of individuals can be affected by nephrolithiasis and/or exercise-induce acute renal failure, and preventive measures can be beneficial 12024214; 14655203; 18492088 SLC22A5 10969 6584 Carnitine deficiency, systemic primary AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic Biochemical; Pharmacogenomic Early disease recognition with prompt carnitine therapy can be immediately life-saving and beneficial long-term; Certain agents (eg, specific antibiotics) have been reported to precipitate severe reactions, and should be avoided 234182; 7432384; 7254270; 7131143; 3974805; 3181209; 3185635; 2235122; 1763895; 2235122; 9826541; 9700603; 11261427; 9634512; 9916797; 11715001; 12210323; 15303004; 16652335; 17126586; 20027113; 20574985; 21922592; 22566287; 22989098; 23379544 SLC24A1 10975 9187 Night blindness, congenital stationary, type 1D AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20850105 SLC24A4 10978 123041 Ameliogenesis imperfecta, hypomaturation type, IIA5 AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23375655; 24621671 SLC24A5 20611 283652 Albinism, oculocutaneous, type VI AR N/A N/A Dermatologic; Ophthalmologic General Variants may also influence relative pigmentation in the general population Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23364476 SLC25A1 10979 6576 Myasthenic syndrome, congenital, 23, presynaptic AR Pediatric Allelic with Combined D-2- and L-2-hydroxyglutaric aciduria (AR) Neurologic General Medical management (with 3,4-DAP) has been reported as beneficial 10963100; 23393310; 23561848; 26870663; 31527857; 31808147 SLC25A10 10980 1468 Mitochondrial DNA depletion syndrome 19 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29211846 SLC25A11 10981 8402 Paragangliomas 6 AD Adult Oncologic Oncologic The condition can involve increased risk of the development of paragangliomas, and awareness may allow early diagnosis and management 29431636 SLC25A12 10982 8604 Developmental and epileptic encephalopathy 39 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19641205 SLC25A13 10983 10165 Citrin deficiency AR Pediatric Biochemical; Gastrointestinal; Hematologic; Neurologic; Oncologic Biochemical; Oncologic The adult-onset form may present after the pediatric interval Dietary (galactose-free diet) and pharmacotherapy (eg, sodium benzoate, sodium phenylbutyrate, and arginine) can be beneficial; Individuals may be at increased risk of hepatocellular carcinoma, and awareness may allow preventive measures, early detection, and treatment; Liver transplantation can be effective 10369257; 11153906; 11281457; 11343052; 11343053; 17323144; 18367750; 12111366; 20301360; 21161389; 21424115; 21914561; 22710133; 22277121; 22892490; 23053473; 23067347; 23112554; 25135652 SLC25A15 10985 10166 Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome AR Pediatric Biochemical; Gastrointestinal; Neurologic Biochemical Dietary (eg, low protein diet,) and medical therapy (eg, with ornithine, citrulline and phenylbutyrate sodium), including during pregnancy, has been reported as beneficial 5782534; 3091924; 3116497; 3670619; 3106719; 3407856; 2222247; 10369256; 11355015; 11552031; 16940241; 18978333; 19242930; 20574716; 22465082; 25135652 SLC25A19 14409 60386 Thiamine metabolism dysfunction syndrome 4; Microcephaly, Amish type AR N/A N/A Biochemical; Neurologic General High fat diet has been reported as being beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12185364; 19798730; 20583149 SLC25A20 1421 788 Carnitine-acylcarnitine translocase deficiency AR Pediatric Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic Biochemical; Cardiovascular Early recognition and dietary/medical treatment in both the immediate and long-term setting (eg, with IV glucose, dialysis, high-carbohydrate/low-fat diet with frequent feeds and medium-chain triglycerdies, and carnitine) can be beneficial; Awareness of potential cardiovascular sequelae can allow prompt recognition and management 1598097; 7807931; 7564255; 8739960; 9399886; 9323572; 9686371; 9544911; 10384385; 15057979; 15365988; 15363639; 16919490; 17277394; 17508264; 21605995; 24088670 SLC25A21 14411 89874 Mitochondrial DNA depletion syndrome 18 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29517768 SLC25A22 19954 79751 Epileptic encephalopathy, early infantile, 3 AR N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15592994; 19780765; 24596948 SLC25A24 20662 29957 Fontaine progeroid syndrome AD N/A N/A Craniofacial; Dermatologic; Genitourinary; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21216154; 29100093; 29100094 SLC25A26 20661 115286 Combined oxidative phosphorylation deficiency 28 AR N/A N/A Biochemical; Cardiovascular; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26522469 SLC25A3 10989 5250 Mitochondrial phosphate carrier deficiency AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17273968 SLC25A32 29683 81034 Exercise intolerance, riboflavin-responsive AR Pediatric Biochemical; Musculoskeletal Biochemical The condition involves recurrent exercise intolerance, and medical management (with oral riboflavin) has been described as being efficacious related to both biochemical and clinical parameters 26933868 SLC25A38 26054 54977 Anemia, sideroblastic 2, pyridoxine-refractory AR Pediatric Hematologic Hematologic Individuals may have chronic, transfusion-dependent anemia refractory to pyridoxine, and diagnosis may allow early transfusion-based treatment 19412178; 21393332 SLC25A4 10990 291 Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 2; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AD/AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Musculoskeletal; Neurologic Cardiovascular; Endocrine Cardiomyopathy has only been described in an individual with a homozygous variant In PEO, individuals have been described with endocrinopathy (eg, thyroid dysfunctiona), and awareness may allow prompt detection and treatment; In Mitochondrial DNA depletion syndrome (cardiomyopathic type), surveillance (eg, with echocardiography/electrocardiography), preventive measures and medical management related to cardiomyopathy may decrease morbidity and mortality 10926541; 11756592; 1756613; 12112115; 12210792; 16155110; 27693233 SLC25A42 28380 284439 Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26541337; 29327420; 29923093 SLC25A46 25198 91137 Neuropathy, hereditary motor and sensory, type VIB with optic atrophy; Pontocerebellar hypoplasia, type 1E AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26168012; 27390132; 27543974; 28637197; 28653766 SLC26A1 10993 10861 Nephrolithiasis, calcium oxalate AR Pediatric Renal Renal Acute renal failure due to calcium oxalate nephrolithiasis has been described, and awareness may allow preventive measures and early diagnosis and management 27210743 SLC26A2 10994 1836 Achondrogenesis, type IB; Atelosteogenesis II; De la Chapelle dysplasia; Diastrophic dysplasia; Epiphyseal dysplasia, multiple, 4 AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13993535; 5703690; 3799721; 4644462; 4064368; 3562108; 8528239; 8571951; 8723083; 8931695; 8723100; 1345170; 7923357; 9108864; 10482955; 10466420; 10465113; 11734236; 11565064; 11303514; 12525546; 12966518; 12220459; 15316973; 18708426; 18925670; 20301483; 20301689; 20525296; 21077202; 21155763; 21922596; 22052783 SLC26A3 3018 1811 Diarrhea 1, secretory chloride, congenital AR Pediatric Gastrointestinal Gastrointestinal Due to copious high-chloride diarrhea individuals may manifest with with dehydration and electrolyte imbalances such as hypokalemia, and metabolic alkalosis, and recognition can allow monitoring of electrolyte and hydration status and appropriate supportive therapy with oral intake of chloride, sodium, and potassium to ensure an appropriate electrolyte balance, as well as medications such as omeprazole to reduce fecal electrolyte output 4162682; 324405; 2651131; 8988888; 11524734; 12442266; 16641574; 17120762; 19861545; 19912155; 19967661; 21332001; 21394828; 21694535; 22277064; 22779076; 23274434 SLC26A4 8818 5172 Pendred syndrome; Deafness, autosomal recessive 4, with enlarged vestibular aqueduct AR Pediatric Audiologic/Otolaryngologic; Endocrine Audiologic/Otolaryngologic; Endocrine Promoter variants have been reported as causative; Digenic inheritance (with KCNJ10) has been reported Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Pendred syndrome, surveillance for and treatment of thyroid abnormalities can be beneficial 9398842; 9500541; 9920104; 10190331; 10902795; 11317356; 14508505; 15689455; 16570074; 17690912; 17503324; 19426954; 21488278; 20301640 SLC26A5 9359 375611 Deafness, autosomal recessive 61 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Heterozygosity has been observed in individuals with hearing loss as well, indicating possible semidominance Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12719379; 24164807 SLC26A8 14468 116369 Spermatogenic failure 3 AD N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23582645 SLC27A4 10998 10999 Ichthyosis prematurity syndrome AR N/A N/A Dermatologic; Obstetric General The obstetric manifestations involve maternal mid-trimester complications of pregnancy leading to prematurity Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19631310; 21856041; 22927265 SLC28A1 11001 9154 Uridine-cytidineuria AR N/A N/A Biochemical General The clinical relevance is unclear 30658162; 30847922 SLC29A3 23096 55315 Histiocytosis-lymphadenopathy plus syndrome AR Pediatric Allelic with Dysosteosclerosis (AR) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Endocrine Lipogranulomatous infiltration has been reported as benefiting from surgical interventions, radiotherapy, and medical treatment (eg, with cylophosphamide, prednisolone); Hormonal insufficiency, including hypogonadotropic hypogonadism, hypothyroidism, and growth hormone deficiency, may benefit from medical treatment; Individuals may manifest with early-onset hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 16118898; 16631937; 16650224; 16155931; 16155931; 18940313; 19336477; 19175903; 19889517; 20140240; 20199414; 20199539; 20399510; 20619369; 21178579; 21888995; 22238637; 22356918; 22653152; 22875837; 22989030; 23058913; 23406517; 23530176; 23623699 SLC2A1 11005 6513 GLUT1 deficiency syndrome 1; GLUT1 deficiency syndrome 2; Dystonia 9; Epilepsy, idiopathic generalized, susceptibility to, 12; Stomatin-deficient cryohydrocytosis with neurologic defects AD/AR Pediatric Hematologic; Neurologic Hematologic; Neurologic Correct diagnosis is important, as ketogenic diet may result in marked clinical improvement of seizures and motor symptoms; Individuals have been described with anemia requiring transfusions; For Dystonia 9, medical management (with acetazolamide and other agents) has been described as beneficial 1575453; 7174793; 8808284; 9462754; 10980529; 11603379; 12555938; 12548383; 15132717; 15180870; 16171377; 15622525; 18451999; 18577546; 19304421; 19630075; 19798636; 19901175; 20574033; 21791420; 21832227; 22282645; 22492876; 23280796; 26336901; 26537434; 28331464 SLC2A10 13444 81031 Arterial tortuosity syndrome AR Pediatric Cardiovascular; Dermatologic; Genitourinary; Musculoskeletal; Renal Cardiovascular Individuals appear to be at increased risk of cradiovascular manifestations, such as ischemic events, arterial aneurysm, and other findings, and preventive measures and prompt treatment may be beneficial 6033167; 12801113; 16550171; 17935213; 18565096; 19508422; 19781076; 29323665 SLC2A2 11006 6514 Fanconi-Bickel syndrome; Glycogen storage disease XI; Neonatal diabetes mellitus AR Pediatric Biochemical; Endocrine; Gastrointestinal; Renal Biochemical; Endocrine Dietary measures (eg, frequent feeds, cornstarch) can be beneficial; In mildly affected individuals, dietary measures (eg, free glucose and galactose restriction) may be beneficial in terms of growth; Individuals may also manifest with neonatal diabetes mellitus, and awareness may allow preventive measures and prompt treatment related to severe episodes 15397919; 6274135; 3153325; 8362811; 7632512; 7564233; 9266402; 9354798; 10987651; 11044475; 11810292; 19480329; 21271664; 22145468; 22350464; 22214819; 22060631; 22831748; 22660720 SLC2A9 13446 56606 Hypouricemia, renal, 2 AD/AR Pediatric Renal Renal The youngest reported individual was an adult, but morbidity could theoretically appear earlier The condition may be associated with complications including exercise-induced acute renal failure and nephrolithiasis, and preventive measures (eg, related to exercise) may be beneficial 9026395; 19926891; 22132964; 21536615 SLC30A10 25355 55532 Hypermanganesemia with dystonia 1 AR Pediatric Biochemical; Gastrointestinal; Hematologic; Neurologic Hematologic The condition can involve hypermagnesemia, with gastrointestinal, neurologic, and other sequelae, and chelation therapy has been described as beneficial in some individuals 11040156; 18087599; 18392750; 21596707; 22341971; 22341972 SLC30A2 11013 7780 Zinc deficiency, transient neonata AD Adult Biochemical Biochemical Infants born to mothers with causative variants can show signs of zinc deficiency, and awareness may allow zinc supplementation in the infant's diet 17065149; 22733820 SLC30A9 1329 10463 Birk-Landau-Perez syndrome AR Pediatric Neurologic; Renal Renal Individuals have been described with childhood-onset renal insufficiency (including hyperkalemia and hypertension) and awaereness may allow early identification and management 28334855 SLC33A1 95 9197 Congenital cataracts, hearing loss, and neurodegeneration AR Pediatric Allelic with Spastic paraplegia 42, autosomal dominant (AD) Audiologic/Otolaryngologic; Biochemical; Neurologic; Ophthalmologic Audiologic/Otolaryngologic; Biochemical Medical treatment (with copper supplementation) has been reported as biochemically and clinically beneficial in some individuals; Awareness of the potential of hearing loss may allow early identification and interventions to support speech and language development 15902551; 19061983; 20461110; 22243965; 22508683 SLC34A1 11019 6569 Fanconi renotubular syndrome 2; Hypercalcemia, infantile 2; Nephrolithiasis/osteoporosis, hypophosphatemic, 1 AR Pediatric Renal Renal In Fanconi renotubular syndrome 4, treatment with neutral phosphate has been reported as resulting in improvement in some but not all clinical, radiological, and laboratory parameters; Due to increased renal phosphate loss, individuals may be at increased risk of renal stone formation and/or bone demineralization; In Hypercalcemia, infantile 2, chronic (with vitamin D supplements) and acute (including IV rehydration, furosemide, corticosteroids, ketoconazole, and oral phosphate) medical management has been described as beneficial in many individuals 2842681; 12324554; 20335586; 26047794 SLC34A2 11020 10568 Pulmonary alveolar microlithiasis AR Pediatric Pulmonary Pulmonary Individuals with cardiovascular valvular anomalies have been described Treatment with disodium editronate has been reported as effective 1485012; 9097354; 9258573; 11287838; 12210357; 12357485; 11956731; 12700375; 16960801; 20425862; 22336687 SLC34A3 20305 142680 Hypophosphatemic rickets with hypercalciuria, hereditary AR Pediatric Renal Renal Heterozygotes may show mild manifestations The condition can result in sequelae such as severe rickets, and supplementation (eg, with phosphate) can be effective to treat many sequelae 2983203; 3796683; 1436310; 16358214; 16358215 SLC35A1 11021 10559 Congenital disorder of glycosylation, type IIf AR Pediatric Allergy/Immunology/Infectious; Hematologic; Neurologic Allergy/Immunology/Infectious; Hematologic Hepatic-metabolized medications should be avoided The condition can include infectious risks (as well as other hematologic anomalies), and antiinnfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been described; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 11157507; 15576474 SLC35A2 11022 7355 Congenital disorder of glycosylation, type IIm XL Pediatric Allergy/Immunology/Infectious; Craniofacial; Hematologic; Neurologic Allergy/Immunology/Infectious; Hematologic Hepatic-metabolized medications should be avoided The condition can include infectious risks (as well as other hematologic anomalies), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 23561849; 24115232 SLC35A3 11023 23443 Arthrogryposis, mental retardation, and seizures AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24031089 SLC35C1 20197 55343 Congenital disorder of glycosylation, type IIc AR Pediatric Allergy/Immunology/Infectious; Biochemical; Neurologic Allergy/Immunology/Infectious; Biochemical; Hematologic Hepatic-metabolized agents should be avoided Treatment with fucose has been described as effective in some individuals; Surveillance for and prompt treatment of infections may be beneficial; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 1279426; 10590041; 11213799; 11326280; 11133780; 12116250; 21175687; 20301507 SLC35D1 20800 23169 Schneckenbecken dysplasia AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11200994; 17952091; 19508970 SLC36A2 18762 153201 Hyperglycinuria; Iminoglycinuria; Iminoglycinuria, digenic AD/AR/Digenic N/A N/A Biochemical; Renal General Variants in other genes (eg, SLC6A18, SLC6A19, SLC6A20) may affect manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19033659 SLC37A4 4061 2542 Glycogen storage disease Ib; Glycogen storage disease Ic; Glycogen storage disease Id AR Pediatric Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Oncologic; Renal Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Oncologic; Renal Dietary measures can be beneficial allow optimal glucose levels and promote growth and development (additionally, specific carbohydrate sources should be limited); Allopurinol to prevent gout and lipid-lowering medications to prevent hyperlipidemia may be necessary when dietary therapy is ineffective; Citrate supplementation and ACE inhibitors may help prevent development of decrease renal complications, though renal transplant may ultimately be necessary; Surveillance for and treatment of hepatic neoplasms (including liver transplant in some) can be beneficial; G-CSF may be beneficial due to recurrent infections 4300573; 212064; 6928812; 6578929; 6298622; 6309784; 3860000; 3459848; 3464427; 2311631; 1719175; 1375344; 8319729; 273986; 8758135; 9428641; 9758626; 9686363; 10931421; 12576310; 20301489; 21575371; 21599942; 21629566 SLC38A8 32434 146167 Foveal hypoplasia 2 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24045842; 24290379 SLC39A13 20859 91252 Ehlers-Danlos syndrome, spondylodysplastic type, 3 AR N/A N/A Craniofacial; Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18985159; 18513683 SLC39A14 20858 23516 Hyperostosis cranialis interna; Hypermanganesemia with dystonia 2 AD/AR Pediatric Biochemical; Musculoskeletal; Neurologic Biochemical; Musculoskeletal In Hyperostosis cranialis interna, surveillance for sequelae related to overgrowth, including hearing evaluation, assessment of signs of increased intracranial pressure and cranial nerve entrapment, can allow early surgical management; In Hypermanganesemia with dystonia 2, individuals have been described with childhood-onset neurodegenerative findings, and medical treatment (with early manganese chelation therapy) has been described as clinically beneficial 20140965; 2300107; 27231142; 29621230 SLC39A4 17129 55630 Acrodermatitis enteropathica AR Pediatric Biochemical; Dermatologic; Gastrointestinal Biochemical Heterozygous variants have been reported as disease-associated in some reports The condition may present with failure to thrive, diarrhea, and dermatitis, and, if untreated, may evolve to include other sequelae of zinc deficiency, including immunodeficiency and neurologic manifestations, and medical management (eg, treatment with oral zinc therapy) can be effective 4136854; 1090826; 12068297; 19370757; 20883266; 21165302; 21762381; 21906148; 21907902; 22082465; 22166942; 23228939; 23430849 SLC39A5 20502 283375 Myopia 24 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24891338 SLC39A8 20862 64116 Congenital disorder of glycosylation, type IIn AR Pediatric Allergy/Immunology/Infectious; Biochemical; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Dietary galactose has been described as having biochemical but unclear clinical benefit Individuals have been described with recurrent infections, and awareness may allow prompt management and prophylactic measures 26637978; 26637979 SLC3A1 11025 6519 Cystinuria AD/AR Pediatric Biochemical; Renal Biochemical; Renal Measures to maintain high fluid intake, as well as medical therapy (eg, urine alkalinization, and, in some, penicillamine) can be beneficial 5925065; 2502678; 8054986; 7573036; 12239244; 12820697; 15635077; 19782624; 20052367; 20399395; 21255007; 21677404; 21863055 SLC40A1 10909 30061 Hemochromatosis, type 4 AD Pediatric Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic Biochemical; Gastrointestinal; Hematologic Biallelic variants (with other hemochromatosis-related genes, such as HFE) have been reported Phlebotomy may be beneficial in some individuals, but genetic diagnosis may be useful to direct treatment regimens, as some indviduals may have reduced tolerance to phlebotomy and can become anemic on therapy despite persistently elevated serum ferritin 1518736; 11431687; 14752817; 14757427; 15030991; 16351644; 15831700; 17566043; 17383046; 19709084; 19342478; 19589941; 20230395; 21175851; 21411349; 22584997; 22890139 SLC41A1 19429 254428 Nephronophthisis-like ciliopathy AR Pediatric Allergy/Immunology/Infectious; Renal Allergy/Immunology/Infectious Renal transplantation has been described Individuals have been described with frequent respiratory infections (including with Pseudomonas aeruginosa in one reported individual), and awareness of infectious risk may allow preventive management as well as prompt and aggressive treatment 23661805 SLC44A1 18798 23446 Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline AR N/A N/A Neurologic; Ophthalmologic General Oral choline treatment did not appear to be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28097321; 31855247 SLC44A4 13941 80736 Deafness, autosomal dominant, 72 AD N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28013291 SLC45A1 17939 50651 Intellectual developmental disorder with neuropsychiatric features (IDDNPF) AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27431290; 28434495 SLC45A2 16472 51151 Oculocutaneous albinism, type IV; Skin/hair/eye pigmentation 5 AD/AR N/A N/A Dermatologic; Ophthalmologic General In Oculocutaneous albinism, type IV, Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing Variants associated with Skin/hair/eye pigmentation 5 are associated with a slight increased risk of skin cancer, but clinical applicability is otherwise unclear 11574907; 14722913; 14961451; 15714523; 17358008; 17999355; 19578363 SLC46A1 30521 113235 Folate malabsorption, hereditary AR Pediatric Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Hematologic; Neurologic Biochemical Individuals may present in infancy with anemia, diarrhea, infections/immune deficiency, and cognitiive impairment, and treatment (eg, with folate/folinic acid supplementation) can be effective 5450108; 3987728; 2381546; 11804211; 11807405; 7129779; 17641272; 18559978; 17446347; 21333572; 21489556 SLC4A1 11027 6521 Spherocytosis, type 4; Ovalcytosis, Southeast Asian; Cryohydrocytosis; Renal tubular acidosis, distal, with hemolytic anemia; Renal tubular acidosis, distal, autosomal dominant; Renal tubular acidosis, distal, autosomal recessive; Blood group, Wright; Blood group, Waldner; Blood group, Diego; Blood group, Froese; Blood group, Swann AD/AR/BG Pediatric Allelic with Acanthocytosis, Band 3 Memphis (AR) Hematologic; Renal Hematologic; Renal In Renal tubular acidosis, if detected early, therapeutic correction of the acidosis by alkali administration leads in most cases to improvement of biochemical abnormalities and resumption of normal growth, as well as beneficial regarding skeletal manifestations; As pertains to hematologic manifestations, splenectomy has been reported as being beneficial; Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 13288586; 13669428; 13739450; 6025225; 2829189; 2146504; 1824272; 1536803; 1519367; 1737855; 1520883; 8343110; 7713501; 8206915; 8282779; 7919393; 7812009; 8547122; 8704215; 8608262; 8567957; 9207478; 9312167; 9734643; 9973643; 9600966; 9854053; 10403343; 10926824; 11061863; 10942416; 11155072; 11380459; 11756190; 12087557; 15211439; 16227998; 19229254; 19297287; 20015879; 20799361; 20825599; 20960171; 22126643; 22609520; 22693689; 22919024; 23255290; 23498825; 23878048; 24257694 SLC4A11 16438 83959 Cryohydrocytosis AD Pediatric Allelic with Corneal dystrophy, Fuchs endothelial 4 (AD); Corneal endothelial dystrophy 2, autosomal recessive (AR); Corneal endothelial dystrophy and perceptive deafness (AR) Audiologic/Otolaryngologic; Hematologic; Ophthalmologic Hematologic Individuals with Cryohydrocytosis can suffer from hemolytic anemia, which can be ameliorated by splenectomy, though postsplenectomy thrombotic complications may occur, and awareness may allow surveillance and management 16767101; 16227998; 17220209; 18024964; 20848555; 21203343; 22072594 SLC4A4 11030 8671 Renal tubular acidosis, proximal, with ocular abnormalities and/or migraine AD/AR Pediatric Dental; Neurologic; Ophthalmologic; Renal Ophthalmologic; Renal Heterozygous variants may result in ophthalmologic anomalies (including glaucoma) and migraine susceptibility Medical treatment of renal tubular acidosis may be beneficial; Diagnosis may allow early treatment related to ocular anomalies, which can include glaucoma 8142230; 10545938; 11274232; 20798035 SLC52A1 30225 55065 Riboflavin deficiency AD Pediatric Biochemical; Neurologic Biochemical Theoretically, biallelic variants could contribute to disease similar to that arising from variants in SLC52A2 or SLC52A3 One individual with a heterozygous deletion has been reported, and this was postulated as contributing to transient neonatal-onset glutaric aciduria Type 2 in this individual's offspring,which was reported as being effectively treated by riboflavin therapy 17689999; 21089064; 23107375 SLC52A2 30224 79581 Brown-Vialetto-Van Laere syndrome 2 AR Pediatric Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic Audiologic/Otolaryngologic; Biochemical Individuals may manifest with progressive neurological dysfunction, and there is evidence that medical/dietary management (with high-dose riboflavin therapy) may be beneficial; Awareness of the potential for hearing loss may allow early interventions related to speech and language development 22740598; 23107375; 23243084; 30343981 SLC52A3 16187 113278 Brown-Vialetto-Van Laere syndrome 1; Fazio-Londe disease AR Pediatric Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic Biochemical Individuals typically manifest with progressive neurological dysfunction, including hearing loss, and there is evidence that high-dose riboflavin therapy may be beneficial in some individuals 13900073; 5969547; 5563586; 7425580; 7229669; 2325091; 16122634; 20206331; 20920669; 21110228; 22098162; 22740598; 22633641; 22211384; 23107375 SLC5A1 11036 6523 Glucose/galactose malabsorption AR Pediatric Gastrointestinal Gastrointestinal Individuals typically present in infancy with severe osmotic diarrhea and consequent dehydration, which can be fatal without dietary elimination of glucose and galactose (ie, individuals demonstrate dramatic improvement on fructose-based formula) 11406349; 2008213; 8985845; 8844006; 9815014; 12139397; 17169300; 18288487; 20486940; 22843301; 23107089; 24048166 SLC5A2 11037 6524 Renal glucosuria AD/AR N/A N/A Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12436245; 21165652 SLC5A5 11040 6528 Thyroid dyshormonogenesis 1 AR Pediatric Endocrine; Oncologic Endocrine; Oncologic Neoplasms have been reported as well as endocrine manifestations Medical treatment of hypothyroidism (eg, with T4) can be effective; Thyroid neoplasms have also been reported, and surveillance may be beneficial 9171822; 19916865; 21543982; 21565787 SLC5A6 11041 8884 Neurodegeneration, infantile-onset, biotin-responsive AR Pediatric Biochemical; Neurologic Biochemical The condition can involve early-onset developmental regression, and medical/dietary treatment (with biotin, pantothenic acid, and alpha-lipoic acid) has been shown to result in clinical improvement 27904971; 31754459 SLC5A7 14025 60482 Myasthenic syndrome, congenital, 20, presynaptic AR Pediatric Allelic with Neuronopathy, distal hereditary motor, type VIIA (AD) Neurologic Neurologic The condition involves muscular weakness, and medical managament (with AChE inhibitors) has been described as beneficial in some individuals 11294660; 23141292; 27569547 SLC6A17 31399 388662 Mental retardation, autosomal recessive 48 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25704603 SLC6A19 27960 340024 Hartnup disease AR Pediatric Variants may be involved in Iminoglycinuria, digenic (digenic) Biochemical; Dermatologic; Neurologic; Renal Biochemical; Dermatologic Medical therapy (nicotinamide) and sun avoidance can be beneficial for pellagra-like findings; Optimal protein-related treatment is unclear 13358233; 5647741; 5813128; 5041315; 2582682; 11394870; 15286787; 15286788; 19033659; 19185582; 19335424; 20399395 SLC6A2 11048 6530 Orthostatic intolerance AD N/A N/A Endocrine; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10684912; 11458707; 12805287 SLC6A20 30927 54716 Iminoglycinuria, digenic; Hyperglycinuria/Iminoglycinuria, modifier of AD/Digenic N/A N/A Biochemical; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19033659 SLC6A3 11049 6531 Parkinsonism-dystonia, infantile 1 AR N/A N/A Neurologic General Described patients demonstrated poor clinical responses to multiple therapeutic agents Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19478460; 22279524 SLC6A5 11051 9152 Hyperekplexia 3 AR Pediatric Neurologic Neurologic Neonates are at risk of sudden death from apnea/aspiration, and surveillance, as well as primary prevention with medical treatments (eg, clonazepam) may be beneficial 1334371; 1355335; 16751771; 22753417; 22700964; 20301437 SLC6A6 11052 6533 Hypotaurinemic retinal degeneration and cardiomyopathy AR Pediatric Biochemical; Cardiovascular; Ophthalmologic Biochemical; Cardiovascular Oral taurine supplementation has been described as being beneficial; Individuals have been described with cardiomyopathy, and awareness may allow early diagnosis and management of cardiac sequelae 31345061; 31903486 SLC6A8 11055 6535 Creatine deficiency syndrome 1 XL Pediatric Audiologic/Otolaryngologic; Biochemical; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic Biochemical Medical treatment (with oral creatine, arginine, and/or glycine supplementation) has been described as beneficial in some patients, as measured by increased cerebral creatine or improved clinical findings 11261517; 11326334; 11898126; 12210795; 12889669; 15154114; 16738945; 17101918; 18569740; 19188083; 20301745; 20501887; 20528887; 20717164; 20846889; 21144783; 21556832; 21660517; 22644605; 22281021; 23660394; 23644449; 24953403 SLC6A9 11056 6536 Glycine encephalopathy with normal serum glycine AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27481395; 27773429 SLC7A14 29326 57709 Retinitis pigmentosa 68 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24670872 SLC7A6OS 25807 84138 Epilepsy, progressive myoclonic, 12 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33085104 SLC7A7 11065 9056 Lysinuric protein intolerance AR Pediatric Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Pulmonary; Renal Biochemical Individuals may manifest with a range of manifestations (eg, developmental delay, failure to thrive with malabsorption, anemia/thrombocytopenia, immunodeficiency, osteoporosis, hemophagocytic lymphohistiocytosis, and pulmonary and renal complications), and dietary/medical therapy (eg, protein restriction, citrulline substitution with use of nitrogen scavengers, lysine supplementation, and carnitine supplementation when necessary) may be beneficial 4158034; 6076999; 5666624; 5431208; 5553484; 7204568; 3917550; 2732736; 8163273; 8655715; 8892019; 10080183; 9931537; 10080182; 10655553; 10737982; 10451527; 17764084; 18328359; 18716612; 20301535; 21308987; 21716135; 22402328; 22876067; 23358709; 23430827; 23542076; 23772603 SLC7A9 11067 11136 Cystinuria AD/AR Pediatric Biochemical; Renal Biochemical; Renal Measures to maintain high fluid intake, as well as medical therapy (eg, urine alkalinization, and, in some, penicillamine) can be beneficial 5925065; 2502678; 10471498; 11157794; 12239244; 12371955; 12820697; 12820697; 17539912 SLC9A1 11071 6548 Spinocerebellar ataxia, autosomal recessive 19 (Lichtenstein-Knorr syndrome) AR N/A N/A Audiologic/Otolaryngologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25205112 SLC9A3 11073 6550 Diarrhea 8, secretory sodium, congenital AR Pediatric Gastrointestinal Gastrointestinal Individuals have been described with severe, early-onset diarrhea and related electrolyte imbalances, and awareness may allow prompt and appropriate management of nutrition and fluid balance 3880821; 26358773; 30633106; 31276831 SLC9A3R1 11075 9368 Nephrolithiasis/osteoporosis, hypophosphatemic, 2 AD Adult Renal Renal Due to increased renal phosphate loss, individuals may be at increased risk of renal stone formation and/or bone demineralization, and preventive measures may be beneficial 18784102 SLC9A6 11079 10479 Mental retardation, X-linked syndromic, Christianson type XL N/A N/A Craniofacial; Neurologic General In addition to other features, retinitis pigmentosa has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10528855; 18342287; 19377476; 20949524; 22931061; 25044251 SLC9A7 17123 84679 Intellectual developmental disorder, X-linked 108 XL N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30335141 SLC9A9 20653 285195 Autism susceptibility 16 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18621663 SLCO1B1 10959 10599 Statin-induced myopathy AD Pediatric Allelic with Hyperbilirubinemia, Rotor type, digenic (Digenic) Gastrointestinal Pharmacogenomic For Hyperbilirubinemia, Rotor type, digenic, inheritance involves SLCO1B1 and SLCO1B3 For Statin-induced myopathy, the presence of variants may indicate an increased risk of adverse events (eg, with statins), or may additionally be associated with indications for dosing/medication selection (eg, with rifampin) 766621; 18781850; 18823304; 18854776; 19238654; 18650507; 19901119; 21178985; 21142914; 19952871; 21243006; 21709081; 21386754; 22462750; 22232210; 22668755; 22749334; 22850760 SLCO1B3 10961 28234 Hyperbilirubinemia, Rotor type, digenic Digenic N/A N/A Gastrointestinal General Inheritance involves SLCO1B1 and SLCO1B3 Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 766621; 22232210 SLCO2A1 10955 6578 Hypertrophic osteoarthropathy, primary, autosomal recessive 2; Primary hypertrophic osteoarthropathy AD/AR N/A N/A Dermatologic; Musculoskeletal General Heterozygotes may show mild manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16283874; 20889364; 22553128; 22331663; 22197487 SLFN14 32689 342618 Bleeding disorder, platelet-type, 20 AR Pediatric Hematologic Hematologic Individuals have increased bleeding tendency, and awareness may allow preventive measures and early management of bleeding complications 26280575; 26769223 SLITRK1 20297 114798 Trichotillomania; Tourette syndrome AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16224024; 17083340; 18021920; 17712845 SLITRK6 23503 84189 Deafness and myopia AR Pediatric Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic Awareness of prelingual hearing loss may allow early interventions related to speech and language development 23543054; 23946138 SLURP1 18746 57152 Mal de Meleda AD/AR N/A N/A Dermatologic General Heterozygotes may display milder manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4281438; 9887370; 11285253; 14756676; 20854438; 21690549; 23290002 SLX4 23845 84464 Fanconi anemia, complementation group P AR Pediatric Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Hematologic; Oncologic Individuals with FA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 21240275; 21240277; 20301575 SMAD3 6769 4088 Aneurysms-osteoarthritis syndrome; Loeys-Dietz syndrome, type 3 AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal Cardiovascular Preventive measures and medical management may be helpful to help decrease morbidity, especially related to cardiovascular complications, which can result in sequelae such as sudden death, primarily due to aortic dissection and/or rupture 21217753; 21778426; 22167769 SMAD4 6770 4089 Hereditary hemorrhagic telangiectasia, type 1; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; Polyposis, juvenile intestinal; Myhre syndrome AD Pediatric Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Hematologic; Oncologic Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Hematologic; Oncologic Individuals with HHT and JPS/HHT may have a variety of vascular complications, including arteriovenous malformations, aortic dilatation, and bleeding diatheses, and surveillance and early intervention related to manifestations (eg, related to thromboembolism or hepatic disease) may decrease morbidity and mortality; In JPS and JPS/HHT, surveillance and early diagnosis/treatment of malignancy (eg, colon cancer) may be beneficial; In Myhre syndrome, individuals may manifest with multisystemic features, including hearing impairment (for which appropriate interventions may be beneficial related to speech and language development) as well as cardiovascular anomalies, and appropriate surveillance may allow prompt diagnosis and treatment 7372073; 7296942; 9582123; 11568925; 12136244; 15031030; 15235019; 16152648; 15723310; 15754356; 16613914; 16690726; 17873119; 18824676; 20101697; 21465659; 21490502; 22158539; 22810475; 21835029; 22243968; 20301525 SMAD6 6772 4091 Aortic valve disease 2 AD Pediatric Allelic with Craniosynostosis 7 (AD/Digenic); Radioulnar synostosis, nonsyndromic (AD) Cardiovascular; Craniofacial; Musculoskeletal; Neurologic Cardiovascular Individuals may manifest with sequelae of cardiovascular anomalies including bicuspid, aortic valve, aortic stenosis, and aortic coarctation, and awareness may allow early detection and medical/surgical management, which may ameliorate morbidity and mortality 22275001; 27606499; 31138930 SMAD9 6774 4093 Pulmonary hypertension, primary 2 AD Pediatric Cardiovascular; Pulmonary Cardiovascular; Pulmonary While prognosis is overall poor, medical therapy (eg, with, oral calcium antagonists, anticoagulants, epoprostenol) may be beneficial, though heart/lung transplantation may be required; Control of complications may be beneficial 19211612 SMARCA2 11098 6595 Blepharophimosis-impaired intellectual development syndrome AD Pediatric Allelic with Nicolaides-Baraitser syndrome (AD) Allergy/Immunology/Infectious; Craniofacial; Dental; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Among other features, the condition can involve recurrent respiratory infections, and awareness may allow preventative measures and early and aggressive treatment of infections 19606471; 22366787; 22822383; 25249037; 32694869 SMARCA4 11100 6597 Rhabdoid tumor predisposition syndrome 2 AD Pediatric Allelic with Mental retardation, autosomal dominant 16 (AD); Coffin-Siris syndrome 4 (AD) Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Genitourinary Oncologic Coffin-Siris syndrome can involve multiple congenital anomalies Individuals may be at high risk for a variety of undifferentiated tumor types, and surveillance and early diagnosis/treatment may be beneficial 20137775; 22426308; 23775540; 24658001; 24658002; 24752781 SMARCAD1 18398 56916 Huriez syndrome AD Adult Allelic with Adermatoglyphia (AD); Basan syndrome (AD) Dermatologic; Oncologic Oncologic Huriez syndrome has been described as involving significant risk of aggressive squamous cell skin carcinoma, and awareness may allow surveillance and early management of disease 4298032; 8731679; 10631162; 20619487; 21820097; 24664640; 24909267; 26932190; 29409814 SMARCAL1 11102 50485 Schimke immunoosseous dysplasia AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Renal Allergy/Immunology/Infectious Though the disorder may be clinically recognizable in many individuals, many individuals have an associated risk for opportunistic infection due to T-cell deficiency, and prophylaxis (eg, against P. carinii) and early and aggressive treatment of infections can be beneficial; BMT has been described 4282260; 2397176; 2066860; 8267014; 9674900; 9632175; 10528861; 10653321; 11113849; 0710226; 11799392; 12471207; 15523612; 16419127; 17089404; 17676601; 20301550 SMARCB1 11103 6598 Schwannomatosis; Rhabdoid tumor predisposition syndrome 1 AD Pediatric Allelic with Mental retardation, autosomal dominant 15 (AD); Coffin-Siris syndrome 3 (AD) Cardiovascular; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Genitourinary Oncologic Coffin-Siris syndrome can involve multiple congenital anomalies Surveillance/early treatment of tumors may reduce morbidity 6091860; 2543225; 9737241; 10521299; 17357086; 18285426; 18072270; 19582488; 20930055; 22426308; 22038540 SMARCC2 11105 6601 Coffin-Siris syndrome 8 AD N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25590979; 27620904; 30580808 SMARCD1 11106 6602 Coffin-Siris syndrome 11 AD N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30879640 SMARCD2 11107 6603 Specific granule defiency 2 AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Hematologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Among other findings, individuals have been described with early-onset severe and recurrent infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT has been described 28369036 SMARCE1 11109 6605 Meningioma, familial, susceptibility to AD Pediatric Allelic with Coffin-Siris syndrome (AD) Craniofacial; Musculoskeletal; Neurologic; Oncologic Oncologic Coffin-Siris syndrome can involve multiple congenital anomalies Awareness of the risk of neoplasms may allow early detection and treatment 23377182; 23906836; 25168959 SMC1A 11111 8243 Cornelia de Lange syndrome 2; Developmental and epileptic encephalopathy 85, with or without midline brain defects XL N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16604071; 20358602; 20635401; 26386245; 26752331; 31334757 SMC3 2468 9126 Cornelia de Lange syndrome 3 with or without midline brain defects AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17273969; 24403048; 31334757 SMCHD1 29090 23347 Bosma arhinia microphthalmia syndrome AD Pediatric Allelic with Facioscapulohumeral muscular dystrophy, type 2 (Digenic, involving a SMCHD1 variant and permissive D4Z4 haplotype) Craniofacial; Endocrine; Musculoskeletal; Ophthalmologic Endocrine The condition involves hypogonadotropic hypogonadism, and in order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 23143600; 28067909; 28067911 SMG8 25551 55181 Alzahrani-Kuwahara syndrome AR N/A N/A Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33242396 SMG9 25763 56006 Heart and brain malformation syndrome AR N/A N/A Cardiovascular; Craniofacial; Neurologic; Ophthalmologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27018474 SMIM1 44204 388588 Blood group, Vel system BG Pediatric Hematologic Hematologic Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 23505126; 23563606; 23563608 SMN1 11117 6606 Spinal muscular atrophy, type I; Spinal muscular atrophy, type II; Spinal muscular atrophy, type III; Spinal muscular atrophy, type IV AR N/A N/A Musculoskeletal; Neurologic General Valproate has been reported as being beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7658877; 8551862; 7813012; 8968751; 8900234; 8782046; 8882869; 9245983; 10735271; 9056553; 10339583; 14705979; 17998484; 16775228; 18337729; 18941424; 19050931; 19716110; 1978076; 20301526 SMN2 11118 6607 Spinal muscular atrophy, modifier of AD N/A N/A Musculoskeletal; Neurologic General Variants in SMN2 are most important in the context of individuals with SMN1 variants Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8900234; 9245983; 11791208; 16508748; 18337729; 18662980; 19716110; 19780763; 20301526 SMO 11119 6608 Pallister-Hall like syndrome AR N/A N/A Cardiovascular; Endocrine; Musculoskeletal; Neurologic Endocrine Interventions related to endocrine abnormalities may be beneficial; Surgical interventions related to hypothalamic hamartoma may be indicated 30497210; 32413283 SMOC1 20318 64093 Microphthalmia with limb anomalies AR N/A N/A Musculoskeletal; Ophthalmologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21194678; 21194680 SMOC2 20323 64094 Dentin dysplasia, type I AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22152679; 23317772 SMPD1 11120 6609 Niemann-Pick disease, type A; Niemann-Pick disease, type B AR N/A N/A Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary General It has been suggested that it could be useful to screen for NPB in heart disease clinics (for patients with very low HDL), or in endocrinology clinics (in individuals with growth retardation) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 13516139; 2023926; 1301192; 1618760; 8664904; 12369017; 15877209; 16434659; 17360762; 17632693; 18815062; 19050888; 19405096; 20301544; 20386867; 22613662 SMPD4 32949 55627 Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies AR Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic Cardiovascular Among other features, individuals have been described with cardiac anomalies, including structural defects as well as cardiomyopathy, and prompt diagnosis may allow early management of these issues and sequelae 31495489 SMPX 11122 23676 Deafness, X-linked 4 XL Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Both prelingual and postlingual onset of deafness has been described, with males described as being affected earlier and more severely Early recognition and treatment of hearing impairment, which may occur in the prelingual stage in some individuals, may improve outcomes, including speech and language development 8872482; 21549336; 21549342; 21893181; 22911656 SMS 11123 6611 Mental retardation, X-linked, Snyder-Robinson type XL N/A N/A Craniofacial; Musculoskeletal; Neurologic Musculoskeletal As with other disorders that manifest with seizures, maximal seizure control is beneficial Individuals manifest with osteoporosis, and calcium supplementation (with ectopic calcification monitoring) and awareness of fracture risk may be beneficial 5823961; 14508504; 18550699; 19206178; 19277733; 21318891; 22612257; 23696453; 23805436 SNAI2 11094 6591 Waardenburg syndrome, type 2D AR Pediatric Allelic with Piebaldism (AD) Audiologic/Otolaryngologic; Dermatologic; Ophthalmologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 1717985; 9450866; 12444107; 12955764 SNAP25 11132 6616 Myasthenic syndrome, congenital 18, with intellectual disability and ataxia AD N/A N/A Musculoskeletal; Neurologic General Treatment with cholinesterase inhibitor was not described as effective Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25381298 SNAP29 11133 9342 Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (CEDNIK syndrome) AR N/A N/A Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15968592 SNCA 11138 6622 Parkinson disease 1; Parkinson disease 4; Dementia with Lewy bodies AD Adult Neurologic Neurologic Levodopa can be beneficial in individuals with Parkinson disease 2158268; 8285594; 9276199; 9197268; 11261505; 14593171; 14755720; 14755719; 16358335; 17251522; 18852448; 18413475; 18195271; 18852449; 18852445; 19139307; 19632874; 21412942; 21800132 SNCAIP 11139 9627 Parkinson disease AD Adult Neurologic Neurologic The pathogenicity of reported variants is unclear Levodopa can be beneficial in individuals with Parkinson disease 12761037; 18366718 SNCB 11140 6620 Dementia with Lewy bodies AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15365127 SNIP1 30587 79753 Psychomotor retardation, epilepsy, and craniofacial dysmorphism AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22279524 SNORD118 32952 727676 Leukoencephalopathy, brain calcifications, and cysts (Labrune syndrome) AR N/A N/A Cardiovascular; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27571260 SNRNP200 30859 23020 Retinitis pigmentosa 33 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16612614; 19878916; 21618346; 23029027 SNRPB 11153 6628 Cerebrocostomandibular syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25047197; 25504470; 26971886 SNRPE 11161 6635 Hypotrichosis 11 AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23246290 SNTA1 11167 6640 Long QT syndrome 12 AD Adult Cardiovascular Cardiovascular Surveillance (eg, with electrocardiography), preventive measures and medical management may be beneficial to decrease morbidity and mortality 10220144; 18591664 SNX10 14974 29887 Osteopetrosis, autosomal recessive 8 AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Dental; Hematologic; Musculoskeletal; Ophthalmologic Musculoskeletal The condition has been described as manifesting with sequelae of osteopetrosis, including failure to thrive related to upper airway issues, as well as complications affecting multiple organ systems, and successful BMT in early childhood has been described 22499339; 23123320 SNX14 14977 57231 Spinocerebellar ataxia, autosomal recessive 20 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24501761; 25439728; 25848753 SOBP 29256 55084 Mental retardation, anterior maxillary protrusion, and strabismus AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17618476; 21035105 SOD1 11179 6647 Amyotrophic lateral sclerosis; Keratoconus; Spastic tetraplegia and axial hypotonia, progressive AD/AR N/A N/A Neurologic; Ophthalmologic General Evidence for involvement with Keratoconus is unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Evidence for pathogenicity is unclear in Keratoconus 8351519; 8105280; 8446170; 7647793; 8592323; 7887412; 15623718; 20577002; 22264771; 22292843; 22292847; 22722621; 31314961; 31332433 SOHLH1 27845 402381 Ovarian dysgenesis 5 AR Pediatric Allelic with Spermatogenic failure 32 (AD) Endocrine; Genitourinary Endocrine Awareness may allow medical management (eg, with combined estrogen-progestin therapy) in order to benefit pubertal development and growth 20506135; 25774885; 28718531 SON 11183 6651 ZTTK syndrome AD N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25590979; 27256762; 27545676; 27545680 SORD 11184 6652 Sorbitol dehydrogenase deficiency with peripheral neuropathy AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32367058 SOS1 11187 6654 Noonan syndrome 4 AD Pediatric Allelic with Fibromatosis, gingival 1 (AD) Cardiovascular; Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic Cardiovascular; Hematologic Surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis and hypertrophic cardiomyopathy) can be beneficial; The condition can include bleeding diathesis, and recognition and preventive measures (eg, in surgical situations) can be beneficial 11868160; 17143285; 17143282; 17586837; 18678287; 18925667; 19047498; 18456719; 19438935; 19077116; 20602484; 20876176; 20301303 SOS2 11188 6655 Noonan syndrome 9 AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic Cardiovascular; Hematologic Surveillance and treatment related to manifestations such as cardiac anomalies (which include pulmonic stenosis) can be beneficial; The condition can include bleeding diathesis, and recognition and preventive measures (eg, in surgical situations) can be beneficial 25795793 SOST 13771 50964 Craniodiaphyseal dysplasia, autosomal dominant; Sclerosteosis 1; van Buchem disease AD/AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal Musculoskeletal Starting in infancy, regular surveillance for sequelae related to overgrowth, including hearing evaluation, assessment of signs of increased intracranial pressure and cranial nerve entrapment, can allow early surgical management 13924477; 3276528; 6323069; 8433139; 9712543; 9463328; 11179006; 11836356; 12116252; 12694228; 14671168; 17245025; 17853455; 20301406; 20583295; 21221996 SOX10 11190 6663 Waardenburg syndrome, type 4C; Waardenburg syndrome, type 2E; Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease; Hirschsprung disease, susceptibility to, 10 AD Pediatric Audiologic/Otolaryngologic; Dermatologic; Gastrointestinal; Genitourinary; Neurologic; Ophthalmologic Audiologic/Otolaryngologic; Gastrointestinal Variants affecting regulatory regions have been implicated in Hirschsprung disease Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In some individuals (such as with Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease), awareness of potential GI complications (eg, chronic intestinal pseudoobstruction) may be beneficial to allow prompt and appropriate management 8911608; 9462749; 10441344; 10077527; 12189494; 17999358; 18348267; 18627047; 22246888; 24357527 SOX11 11191 6664 Coffin-Siris syndrome 9 (Mental retardation, autosomal dominant 27) AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24886874 SOX17 18122 64321 Vesicoureteral reflux 3 AD Pediatric Renal Renal Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function 20960469 SOX18 11194 54345 Hypotrichosis-lymphedema-telangiectasia syndrome; Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome AD/AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Neurologic; Renal General Renal transplantation has been described in Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2484451; 12740761; 24697860 SOX2 11195 6657 Microphthalmia, syndromic 3 AD Pediatric Craniofacial; Dental; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Individuals may demonstrate endocrine anomalies such as growth hormone deficiency, and early recognition and treatment may be beneficial Individuals may demonstrate endocrine anomalies such as growth hormone deficiency, and early recognition and treatment may be beneficial 10564870; 12002146; 12612584; 12749061; 15346919; 16145681; 15389708; 15812812; 16283891; 16470798; 16932809; 16543359; 16892407; 19254784; 17219395; 18831064; 19921648; 20301477; 20301552; 20803647 SOX3 11199 6658 Panhypopituitarism, X-linked XL Pediatric Allelic with Mental retardation, X-linked, with isolated growth hormone deficiency (XL), which may be recognizable, and early recognition may not necessarily be additionally helpful Endocrine; Musculoskeletal; Neurologic Endocrine Deletions/insertions involving SOX3 regulatory regions can result in 46,XX sex reversal 3 (XL) or Hypoparathyroidism, X-linked by a position effect (XL) Treatment for endocrine deficiencies, including those resulting in neonatal electrolyte abnormalities, may be beneficial 8826446; 9106538; 11031100; 12428212; 15800844; 16167084; 17400794; 21183788 SOX4 11200 6659 Coffin-Siris syndrome 10 AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30661772 SOX5 11201 6660 Lamb-Shaffer syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22290657; 23220431; 23498568; 26111154 SOX6 16421 55553 Tolchin-Le Caignec syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32442410 SOX9 11204 6662 46, XY sex reversal 10; Campomelic dysplasia AD Pediatric Allelic with 46,XX sex reversal 2 (AD), which has been reported as resulting from SOX9 promoter anomalies or cytogenetic aberrations Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Oncologic; Renal; Genitourinary Oncologic; Genitourinary The condition can involve multiple congenital anomalies Individuals with a 46,XY karyotype and genital undermasculinization should undergo gonadal removal due to risk of gonadoblastoma 10588843; 20301724; 21208124; 25604083 SP110 5401 3431 Hepatic venoocclusive disease with immunodeficiency AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Neurologic Allergy/Immunology/Infectious Mortality is high if the condition is unrecognized; interventions include intravenous immunoglobulin and infectious prophylaxis (Pneumocystis jerovici) 16648851; 17510920; 22621957; 22982295 SP7 17321 121340 Osteogenesis imperfecta, type XII AR N/A N/A Dental; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20579626 SPARC 11219 6678 Keratoconus; Osteogenesis imperfecta, type XVII AD/AR N/A N/A Musculoskeletal; Ophthalmologic General Evidence for pathogenicity of the described variants is unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21976959; 26027498 SPART 18514 23111 Spastic paraplegia 20, autosomal recessive (Troyer syndrome) AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6022528; 12134148; 18413476; 20437587; 26003402 SPAST 11233 6683 Spastic paraplegia 4, autosomal dominant AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9302257; 9736780; 10699187; 11134375; 11843700; 11309678; 12471215; 15159500; 15210521; 15248095; 14872021; 16682546; 16055926; 16832076; 17345589; 17098887; 17895902; 18401025; 19652142; 18701882; 19939411; 20301339; 20562464; 20932283; 21659953; 21834905; 22192498; 22960362 SPATA16 29935 83893 Spermatogenic failure 6 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17847006 SPATA5 18119 166378 Epilepsy, hearing loss, and mental retardation syndrome (EHLMRS) AR Pediatric Allelic with Schizophrenia (AD) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Hematologic; Neurologic Allergy/Immunology/Infectious; Audiologic/Otolaryngologic Although details are unclear, multiple individuals have been described as having immunodefiency, and awareness may allow prompt and aggressive treatment of infections; Among other findings, the condition can include sensorineural hearing loss, and some patients may benefit from early recognition and management of hearing loss 21822266; 26299366 SPATA7 20423 55812 Leber congenital amaurosis 3; Retitinitis pigmentosa, juvenile, SPATA7-related AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9799089; 18936139; 19268277; 21310915 SPECC1L 29022 23384 Facial clefting, oblique, 1; Opitz GBBB syndrome, type II; Hypertelorism, Teebi type AD N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3398011; 17506099; 21703590; 25412741; 26111080 SPEF2 26293 79925 Spermatogenic failure 43 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31048344; 31151990; 31278745 SPEG 16901 10290 Centronuclear myopathy 5 AR Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic Cardiovascular The condition may include cardiomyopathy, and recognition may allow early management, which has been described as effectve in affected individuals 25087613 SPEN 17575 23013 Radio-Tartaglia syndrome AD N/A N/A Cardiovascular; Craniofacial; Endocrine; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33596411 SPG11 11226 80208 Amyotrophic lateral sclerosis 5, juvenile recessive; Charcot-Marie-Tooth disease, axonal, type 2X; Spastic paraplegia 11 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17717710; 18067136; 17322883; 18663179; 18787847; 19196735; 19194956; 19513778; 20108361; 20110243; 20301389; 20390432; 20571989; 20971220; 21035867; 21381113; 21625935; 22154821; 22175763; 23043354; 23121729; 26556829 SPG21 20373 51324 Spastic paraplegia 21 (Mast syndrome) AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6024251; 14564668; 20301682; 24451228 SPG7 11237 6687 Spastic paraplegia 7, autosomal recessive AR N/A N/A Neurologic General Heterozygotes may demonstrate manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9635427; 9634528; 16534102; 18200586; 18799786; 20108356; 21623769; 22571692; 22964162 SPINK1 11244 6690 Pancreatitis, hereditary AD Pediatric Gastrointestinal; Oncologic Gastrointestinal; Oncologic Dietary measures (eg, low-fat diet with frequent feeding), hydration, and antioxidants, with avoidance of precipitants such as alcohol and tobacco, can beneficial in order to ameliorate episodes of pancreatitis; Individuals may be at high risk of pancreatic cancer, and awareness may allow early diagnosis and treatment 2813331; 10691414; 10835640; 11938439; 12011155; 16492714; 17274009; 18184119; 18755888; 20543535; 20664488; 21610753; 20676769; 21415673; 21375584; 20977904; 22228370; 24624459 SPINK2 11245 6691 Spermatogenic failure 29 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28554943 SPINK5 15464 11005 Netherton syndrome AR Pediatric Allergy/Immunology/Infectious; Dermatologic Allergy/Immunology/Infectious; Dermatologic The condition may not always be readily recognizable; Recurrent bacterial infections are common, and prophylactic measures, as well as prompt and aggressive treatment of infections may be beneficial; Hypernatremic dehydration in the neonatal period can result in severe sequelae, and awareness may allow preventive measures and prompt medical management 13582191; 7822652; 10835624; 11841556; 11693786; 17608759; 19683336; 20107740; 21573681; 21564178; 21692842; 22377713; 22837558; 23331056 SPINT2 11247 10653 Diarrhea 3, secretory sodium, congenital, with or without other congenital anomalies AD Pediatric Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic Gastrointestinal Due to fecal sodium loss, individuals may present with severe (potentially lethal) secretory diarrhea and related electrolyte/metabolic derangements, including hyponatremic metabolic acidosis, and recognition may allow appropriate medical management, which includes parenteral nutrition (weaning from parenteral nutrition, with oral sodium citrate supplementation, is possible in childhood 11113072; 17786112; 19185281; 20009592 SPNS2 26992 124976 Deafness, autosomal recessive, 115 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 30973865 SPOP 11254 8405 Nabais Sa-de Vries syndrome type 2 (Neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies) AD Pediatric Allelic with Nabais Sa-de Vries syndrome type 1 (Neurodevelopmental disorder with microcephaly and dysmorphic facies) (AD) Cardiovascular; Craniofacial; Endocrine; Neurologic; Ophthalmologic Cardiovascular; Endocrine The condition can include structural cardiovascular anomalies, and awareness may allow early detection and management; Endocrine abnormalities, including hypothyroidism, have been described, and awareness may allow early detection and management 32109420 SPR 11257 6697 Dystonia, Dopa-responsive, due to sepiapterin reductase deficiency AR Pediatric Biochemical; Neurologic Biochemical The condition may be frequently mistaken for nonspecific findings such as idiopathic "cerebral palsy", and many individuals benefit from medical therapy (eg, levodopa/carbidopa, 5-hydroxytryptophan) 11443547; 7159114; 18502672; 19130291; 20222129; 21431957; 22291068; 22522443; 22018912; 26123188 SPRED1 20249 161742 Legius syndrome AD N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Oncologic processes are reported in some individuals, but the overall risk is unclear, and it has been stated that the condition does not involve tumor predisposition Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17704776; 19366998; 19443465; 19920235; 20179001; 21649642; 21548021; 20945555; 22753041; 23401230 SPRY2 11270 10253 IgA nephropathy, susceptibility to, 3 AD N/A N/A Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25782674 SPRY4 15533 81848 Hypogonadotropic hypogonadism 17, with or without anosmia AD/Digenic Pediatric Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal; Neurologic Endocrine Relatively complex genetic models of disease have been described (eg, involving variants in other FGF8-network-associated genes) In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 23643382 SPTA1 11272 6708 Spherocytosis, type 3; Pyropoikilocytosis , hereditary; Ellipsocytosis 2 AD/AR Pediatric Hematologic Hematologic Individuals have been described with severe hemolytic anemia, which has been treated by interventions such as frequent transfusions and splenectomy 1191563; 7070419; 2987946; 3785322; 3597773; 2567189; 2794061; 1541680; 8226774; 8941647; 16150946; 21251457 SPTAN1 11273 6709 Epileptic encephalopathy, early infantile, 5 AD N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18469812; 18065176; 20493457; 22258530 SPTB 11274 6710 Spherocytosis, type 2; Ellipsocytosis 3 AD/AR Pediatric Hematologic Hematologic Some individuals may have severe, transfusion-requiring anemia, and splenectomy may also be beneficial 4426130; 7229027; 7119110; 7104494; 4052329; 3276733; 2807277; 2346784; 2070088; 1391962; 8102379; 8226774; 7883966; 8675627; 8844207; 9075575; 9005995; 9163587; 9414314; 9450796; 9609518; 9887280; 11703334; 19538529 SPTBN2 11276 6712 Spinocerebellar ataxia 5, autosomal dominant; Spinocerebellar ataxia 14, autosomal recessive AD/AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16429157; 23236289; 23838597 SPTBN4 14896 57731 Spherocytosis, type 3; Pyropoikilocytosis, hereditary; Ellipsocytosis 2 AR N/A Allelic with Myopathy, congenital, with neuropathy and deafness (AR) Audiologic/Otolaryngologic; Craniofacial; Hematologic; Musculoskeletal; Neurologic General Individuals with Spherocytosis, Pyropoikilocytosis, and Ellipsocytosis have been described with severe hemolytic anemia, which has been treated by interventions such as frequent transfusions and splenectomy 1191563; 7070419; 2987946; 3785322; 3597773; 2567189; 2794061; 1541680; 8226774; 8941647; 16150946; 21251457; 28540413 SPTLC1 11277 10558 Neuropathy, hereditary sensory and autonomic, type IA; Neuropathy, hereditary sensory and autonomic, type IC AD Pediatric Neurologic Neurologic The condition involves sensory neuropathy with variable autonomic and motor involvement, and medical management (eg, with oral serine supplementation) has been reported as resulting in laboratory-based and clinical benefits 11242106; 11242114; 12417569; 15037712; 19132419; 20920666; 22045570; 22302274; 30626650; 31509666 SPTLC2 11278 9517 Neuropathy, hereditary sensory and autonomic, type IC AD Pediatric Neurologic Neurologic The condition involves sensory neuropathy with variable autonomic and motor involvement, and medical management (eg, with oral serine supplementation) has been reported as resulting in laboratory-based and clinical benefits 20920666; 23658386; 26681808; 30626650; 30866134; 30955194 SPZ1 30721 84654 Ciliary dyskinesia, primary, 38 AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary Audiologic/Otolaryngologic; Pulmonary Among other findings, patients can manifest with early-onset respiratory disease, including upper respiratory infections, and awareness may allow early interventions related to these sequelae 29727692; 29727693 SQOR 20390 58472 Sulfide:quinone oxidoreductase deficiency AR Pediatric Biochemical; Neurologic Biochemical The condition can involve neurometabolic sequelae, and adequate caloric intake with fasting avoidance has been recommended; Medical management. (eg, with hydroxycobalamin and methylene blue) has been suggested as potentially beneficial 32160317 SQSTM1 11280 8878 Paget disease of bone 3 AD Pediatric Allelic with Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (AD); Myopathy, distal, with rimmed vacuoles (AD); Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset (AR) Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Oncologic Musculoskeletal; Oncologic Medical management (eg, inhibitors of osteoclastic bone resorption) can be beneficial - bisphosphonates are the current first line of treatment; Awareness of the risk of related oncologic processes (eg, osteosarcoma) may be beneficial to allow early treatment 9626117; 11123042; 12374763; 11992264; 15176995; 18620951; 21735147; 22024254; 22084127; 22972638; 24042580; 24486447; 26208961; 27545679 SRC 11283 6714 Thrombocytopenia, autosomal dominant, 6 AD Pediatric Hematologic; Musculoskeletal Hematologic Individuals have been described with bleeding diathesis, including after dental/surgical procedures, and awareness may allow preventive measures and prompt treatment 26936507 SRCAP 16974 10847 Floating-Harbor syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7588969; 16523514; 20358590; 22265015; 23763483 SRD5A2 11285 6716 Steroid 5-alpha-reductase 2 deficiency AR Pediatric Endocrine; Genitourinary; Oncologic Endocrine; Genitourinary; Oncologic Hormonal treatment may be beneficial related to phenotypic gender characteristics; Due to risk of gonadal malignancy, prophlactic measures (related to gonadal tumors) may be beneficial 4432067; 431680; 1944596; 1406794; 1522235; 8262007; 7554313; 8626825; 8768837; 8606628; 8723114; 8789759; 9208814; 9066886; 9467575; 9745434; 10564874; 10999800; 10718838; 11869378; 12576851; 12699446; 12713261; 12843198; 15813602; 16098368; 16181229; 17551467; 18391525; 17609295; 18717241; 18314109; 18350250; 20511729; 20019388; 20132346; 20395661; 21147889; 20850730; 22001134; 22453073 SRD5A3 25812 79644 Kahrizi syndrome; Congenital disorder of glycosylation, type Iq AR Pediatric Biochemical; Cardiovascular; Craniofacial; Dermatologic; Endocrine; Hematologic; Neurologic; Ophthalmologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 18271001; 18781183; 20637498; 20700148 SREBF1 11289 6720 Ichthyosis follicularis, atrichia, and photophobia syndrome 2; Mucoepithelial dysplasia, hereditary AD N/A N/A Dermatologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31790666; 32497488; 32902915 SRP54 11301 6729 Neutropenia, severe congenital, 8, autosomal dominant AD Pediatric Allergy/Immunology/Infectious; Hematologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Individuals have been described with recurrent infections, and awareness may allow prompt management and prophylactic measures; HSCT has been described 28972538; 29914977 SRP72 11303 6731 Bone marrow failure syndrome 1 AD Pediatric Audiologic/Otolaryngologic; Hematologic; Oncologic Audiologic/Otolaryngologic; Hematologic; Oncologic Individuals have been described as having early-onset anemia/panyctopenia, as well as later myelodysplasia, and measures to detect and ameliorate hematologic findings may be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 22541560 SRPX2 30668 27286 Rolandic epilepsy, mental retardation, and speech dyspraxia XL N/A N/A Neurologic General The evidence of variants as being related to disease causation has been questioned due to subsequent population-based studies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16497722; 23871722; 24995671 SRY 11311 6736 46,XY disorder of sex development; 46, XX disorder of sex development YL Pediatric Endocrine; Genitourinary; Oncologic Genitourinary; Oncologic Treatment depends on sex chromosome complement; Hormonal treatment may be beneficial (eg, with hormone replacement therapy at the onset of puberty) In individuals with 46, XY, karyotype, due to increased risk for gonadal tumors, abdominal dysgenetic gonads and streak gonads should be surgically removed 2247151; 7904700; 8472885; 1956279; 1734522; 1639410; 1570829; 20301714; 20301589 SSBP1 11317 6742 Optic atrophy 13 with retinal and foveal abnormalities AD N/A N/A Audiologic/Otolaryngologic; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31298765; 31550237; 31550240 SSR4 11326 6748 Congenital disorder of glycosylation, type Iy XL N/A N/A Biochemical; Craniofacial; Musculoskeletal; Neurologic General Hepatic-metabolized agents should be avoided Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24218363; 26264460 SSTR5 11334 6755 Resistance to somatostatin treatment AD Pediatric General Pharmacogenomic The presence of variants may impact the use of medications to treat conditions such as acromegaly 11502816; 15914528; 21744088; 21810856 ST14 11344 6768 Ichthyosis, congenital, autosomal recessive 11 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17273967; 18445049; 18843291 ST3GAL3 10866 6487 Intellectual development disorder, autosomal recessive 12; Developmental and epileptic encephalopathy 15 AR N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17120046; 21907012; 23252400 ST3GAL5 10872 8869 Salt and pepper developmental regression syndrome (Ganglioside GM3 synthase deficiency) AR N/A N/A Dermatologic; Neurologic; Ophthalmologic General Treatment with ubiquinone has been described, but the overall efficacy is unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4213132; 15502825; 22990144; 23436467 STAC3 28423 246329 Myopathy, congenital, Baily-Bloch AR Pediatric Craniofacial; Musculoskeletal Musculoskeletal; Pharmacogenomic Among other findings, individuals have been described with susceptibility to malignant hyperthermia related to anesthesia, and awareness may allow preventive measures 23736855 STAG1 11354 10274 Mental retardation, autosomal dominant 47 AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency 28119487 STAG2 11355 10735 Mullegama-Klein-Martinez syndrome (Neurodevelopmental disorder, X-linked, with craniofacial abnormalities); Holoprosencephaly 13, X-linked XL N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28296084; 29263825; 30158690; 30447054; 30765867; 31334757 STAG3 11356 10734 Premature ovarian failure 8 AR Pediatric Endocrine; Obstetric Obstetric One described individual was reported as additionally affected by ovarian cancer Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency 22428046; 24597867; 26059840 STAMBP 16950 10617 Microcephaly-capillary malformation syndrome AR N/A Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23542699 STAR 11359 6770 Lipoid adrenal hyperplasia AR Pediatric Endocrine; Genitourinary; Oncologic Endocrine; Genitourinary; Oncologic Due to the severity of disease, most individuals present as phenotypic females with fatal salt-wasting adrenal crises if untreated in early infancy (patients may also present later in life with milder forms of disease), and medical treatment (eg, with glucocorticoid and mineralcorticoid replacement) may be beneficial; Treatment of genitourinary anomalies (eg, with surgery, including related to the risk of malignancy in genotypic males) may be indicated in some individuals 13968788; 4685387; 3841304; 2419119; 1661294; 7892608; 7547998; 8948562; 9077535; 10323391; 11061515; 16968793; 21057961; 21691971; 21714456; 21846663; 22028173; 22083155; 22249004 STARD7 18063 56910 Epilepsy, familial adult myoclonic, 2 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31664034 STAT1 11362 6772 Immunodeficiency 31A; Immunodeficiency 31B; Immunodeficiency 31C AD/AR Pediatric Allergy/Immunology/Infectious; Oncologic Allergy/Immunology/Infectious; Oncologic Individuals with autosomal recessive forms demonstrate susceptibility to severe viral and mycobacterial infections (including lethal infections), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals with heterozygous forms may besusceptible to candiasis, and may be susceptible to neoplasms including carcinoma, as well as autoimmune thyroid disease, and awareness may allow prompt diagnosis and treatment; HSCT has beeen described in some STAT1-related conditions 4213132; 15502825; 22990144; 23436467; 24026681; 27232954; 30691927 STAT2 11363 6773 Immunodeficiency 44; Pseudo-TORCH syndrome 3 AR Pediatric Allergy/Immunology/Infectious; Biochemical; Renal Allergy/Immunology/Infectious Individuals with both conditions can demonstrate infection susceptibility, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; In Immunodeficiency 44, adverse reactions to vaccinations have been reported, and awareness may help prevent morbidity; In Pseudo-Torch syndrome 3, the use of immunologic medical treatments (eg, dexamethasone, ruxolitinib) has been described as showing some benefit; HSCT has been described in Pseudo-Torch syndrome 3 23391734; 26122121; 31836668; 32092142 STAT3 11364 6774 Hyper-IgE recurrent infection syndrome 1, autosomal dominant; Autoimmune disease, multisystem, infantile onset 1 AD Pediatric Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Musculoskeletal; Oncologic Allergy/Immunology/Infectious; Cardiovascular; Oncologic In Hyper-IgE recurrent infection syndrome, among other manifestations, individuals may suffer recurrent mucocutaneous and pulmonary infections, and antintiinfectious prophylaxis (eg, antibiotics, antifungals, and IgG infusions), as well as early and aggressive treatment of infections may be beneficial; The condition may include vascular anomalies, and awareness may be beneficial in management; Individuals may also have susceptibility to malignancies such as non-Hodgkin lymphoma, and awareness may allow early diagnosis and treatment; In Autoimmune disease, multisystem, infantile onset, individuals have been described with immunodeficiency, and awareness may allow antiinfectious prophylaxis as well as early and aggressive treatment of infections; Awarness of sequelae of autoimmune disease (eg, resulting in hypothyroidism) may allow early management of such manifestations 4161105; 5059313; 6806658; 10053178; 17881745; 17676033; 17942886; 21703716; 22084479; 22751495; 25038750 STAT5B 11367 6777 Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant; Growth hormone insensitivity with immune dysregulation 1, autosomal recessive AD/AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal Allergy/Immunology/Infectious; Endocrine In Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant, medical management (eg, with growth or hormone or recombinant human IGF-1) might be effective, though this remains to be fully evaluated; Individuals with Growth hormone insensitivity with immune dysregulation 1, autosomal recessive demonstrate infection susceptibility, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; As relates to growth deficiency in Growth hormone insensitivity with immune dysregulation 1, autosomal recessive, medical management (eg, with with recombinant human IGF-1) may be beneficial 8977385; 13679528; 15827093; 17030597; 16787985; 17389811; 21396575; 22423513; 22678306; 29844444 STEAP3 24592 55240 Hypochromic microcytic anemia with iron overload 2 AD Pediatric Endocrine; Hematologic Endocrine; Hematologic Individuals have been described with transfusion-dependent anemia; The condition may involve primary endocrine anomalies, and surveillance for involvement (eg, adrenal failure or thyroid insufficiency) may benefit medical management 22031863 STEEP1 26239 63932 Mental retardation, X-linked, 107 XL N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29374277 STIL 10879 6491 Microcephaly, primary autosomal recessive, 7 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19215732; 20978018; 25218063 STIM1 11386 6786 Stormorken syndrome; Immunodeficiency 10 AD/AR Pediatric Allelic with Myopathy, tubular aggregate 1 (AD) Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Dental; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Cardiovascular; Hematologic In Stormorken syndrome, individuals may demonstrate hematologic anomalies including anemia, thrombocytopenia, and bleeding diathesis, and awareness may allow preventive measures and prompt treatment; Individuals have been described with cardiovascular anomalies (eg, intracranial aneurysms), and awareness may allow surveillance and early management; In Immunodeficiency 10, individuals may suffer early and severe (including fatal) infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals may have hematologic abnormalities, including autoimmune hemolytic anemia and thrombocytopenia, which have been reported as steroid-responsive; HSCT has been reported 19420366; 20876309; 22190180; 23332920; 24570283; 24591628; 24619930; 25577287 STING1 27962 340061 STING-associated vasculopathy, infantile-onsent (SAVI) AD N/A N/A Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Hematologic; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25029335; 25401470 STK11 11389 6794 Peutz-Jeghers syndrome AD Pediatric Dermatologic; Gastrointestinal; Oncologic Gastrointestinal; Oncologic Routine surgical/endoscopic procedures can decrease the need of emergent procedures for sudden and severe sequelae (eg, intussusception); Surveillance for and early treatment of a variety of common malignancies (individuals may be at increased risk of a number of types of epithelial malignancies, including breast, cervical adenoma malignum, colorectal, gastric, ovarian, pancreatic cancers, sex cord tumors with annular tubules, and testicular Sertoli cell tumors) can be beneficial 15399020; 14214503; 14279723; 5466889; 990720; 7436458; 3943856; 3697923; 3587280; 3181678; 2599445; 1986290; 7776109; 7802138; 9850045; 9428765; 9425897; 10408777; 10689645; 10874301; 11389158; 12044140; 15121768; 15200509; 15863673; 15617552; 20581245; 20301443 STK4 11408 6789 T-cell immunodeficiency syndrome, recurrent infections, autoimmunity, with or without cardiac malformations AR Pediatric Allergy/Immunology/Infectious; Cardiovascular Allergy/Immunology/Infectious; Cardiovascular Individuals are susceptible to recurrent and severe viral, bacterial, and fungal infections (as well as sequelae such as EBV-related lymphoma), and and prophylaxis, as well as prompt and aggressive treatment of infections may be beneficial; Individuals may have cardiovascular anomalies, and surveillance (including with echocardiogram) may allow early detection and management; HSCT has been described 22294732; 22174160 STN1 26200 79991 Cerebroretinal microangiopathy with calcifications and cysts 2 AR Pediatric Cardiovascular; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic Cardiovascular; Gastrointestinal; Hematologic Among other features, individuals have been described with gastrointestinal bleeding, and awareness may allow medical management (eg, with thalidomide treatment and argon plasma coagulation) as well as prompt treatment of urgent situations; RBC transfusions have been described as necessary due to bone marrow failure 27432940 STRA6 30650 64220 Microphthalmia, syndromic 9 AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11857549; 17503335; 17236193; 17273977; 19112531; 19213032; 19309693; 21901792; 22283518; 22686418 STRADA 30172 92335 Polyhydramnios, megalencephaly, and symptomatic epilepsy AR N/A N/A Cardiovascular; Endocrine; Neurologic; Obstetric; Renal General The condition can involve multiple congenital anomalies and can affect the pregnancy (due to polyhydramnios) with the affected individual Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17522105 STRC 16035 161497 Deafness, autosomal recessive 16 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 9429146; 10090914; 11687802; 21686705; 19246478 STS 11425 412 Steroid sulfatase deficiency XL Pediatric Biochemical; Dermatologic; Obstetric; Oncologic; Ophthalmologic; Genitourinary Obstetric; Oncologic; Genitourinary In pregnancy, affected females may manifest with birth/delivery complications, such as failure to progress in labor, and awareness may allow improved planning and management of pregnancy and delivery; Individuals are at risk for testicular cancer, and awareness may allow preventive measures/early management, which may decrease morbidity and mortality 3864397; 5303230; 5307231; 6135610; 6140547; 6234482; 6652948; 6135610; 6929654; 6482910; 2866054; 3480263; 3480541; 3032454; 1539590; 7546451; 9252398; 10583107; 10692123; 11477606; 16191859; 16403384; 18076704; 19200188; 20236202; 21530180; 22419362; 22486194; 23442483 STT3A 6172 3703 23842455; 28424003 AR N/A N/A Biochemical; Neurologic General Hepatic-metabolized agents should be avoided Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23842455 STT3B 30611 201595 Congenital disorder of glycosylation, type Ix AR N/A N/A Biochemical; Gastrointestinal; Genitourinary; Hematologic; Neurologic; Ophthalmologic Hematologic Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 23842455 STUB1 11427 10273 Spinocerebellar ataxia 48; Spinocerebellar ataxia, autosomal recessive 16 AD/AR N/A N/A Neurologic General Hypogonadism has been described in some individuals with Spinocerebellar ataxia, autosomal recessive 16 Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24312598; 24113144; 24719489; 24742043; 25258038; 30381368 STX11 11429 8676 Hemophagocytic lymphohistiocytosis, familial, 4 AR Pediatric Allergy/Immunology/Infectious; Neurologic; Oncologic Allergy/Immunology/Infectious; Oncologic Some individuals have been described as having remission without treatment; It has been suggested that variants may also confer risk for other malignancies. Antibiotics or antiviral agents can be beneficial to treat/prevent infections that can trigger an exaggerated inflammatory response. Chemo/immunotherapy can achieve clinical stability prior to allogeneic hematopoietic cell transplantation (HCT), the only curative therapy. 15703195; 16278825; 16582076; 24459464 STX16 11431 8675 Pseudohypoparathyroidism, type IB AD Pediatric Endocrine; Renal Endocrine; Renal Complications such as osteitis fibrosa cystica may be effectively treated with calcium and vitamin D therapy 15537666; 17595244; 18626245; 20960161; 20538864; 21752878 STX1B 18539 112755 Generalized epilepsy with febrile seizures plus, type 9 AD N/A N/A Neurologic General As with many disorders involving seizure risk, optimal control is beneficial, and genetic diagnosis may be beneficial related to medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11591834; 18479394; 25362483 STXBP1 11444 6812 Developmental and epileptic encephalopathy 4 AD N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18469812; 18065176; 19557857; 20876469; 21062273; 21376300; 21762454; 21770924; 22596016; 23020937; 24623842 STXBP2 11445 6813 Hemophagocytic lymphohistiocytosis, familial 5 AR Pediatric Allergy/Immunology/Infectious; Neurologic Allergy/Immunology/Infectious Antibiotics or antiviral agents can be beneficial to treat/prevent infections that can trigger an exaggerated inflammatory response. Chemo/immunotherapy can achieve clinical stability prior to allogeneic hematopoietic cell transplantation (HCT), the only curative therapy. 19804848; 19884660; 20798128 SUCLA2 11448 8803 Mitochondrial DNA depletion syndrome 5 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic; Renal Audiologic/Otolaryngologic Features such as frequent infections and cardiomyopathy have been described in some individuals Early recognition and treatment (eg, with cochlear implants) of hearing impairment, which may occur in the prelingual stage, may improve outcomes, including speech and language development 15877282; 19015156; 17301081; 17287286; 19015156; 19666145; 20301762; 23010432 SUCLG1 11449 8802 Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17668387; 19526370; 20693550; 21093335; 21639866 SUFU 16466 51684 Medulloblastoma; Basal cell nevus syndrome AD Pediatric Allelic with Joubert syndrome 32 (AR) Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic Oncologic Individuals are at risk for a number of types of malignancies (including medulloblastoma), and surveillance may allow early diagnosis and treatment (including with molecular therapies that target the Hedgehog signaling pathway), potentially reducing morbidity and mortality; Avoidance of agents such as radiation therapy is indicated 12068298; 19533801; 19833601; 21188540; 22670903; 22670904; 28965847 SUGCT 16001 79783 Glutaric aciduria III AR N/A N/A Biochemical General The clinical significance of the condition is unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1909402; 12555941; 18926513 SULT2B1 11459 6820 Ichthyosis, congenital, autosomal recessive 14 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28575648 SUMF1 20376 285362 Multiple sulfatase deficiency AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic The condition can include hearing loss, and hearing testing has been recommended; Due to risk of cardiovascular sequelae, screening with electrocardiogram and echocardiogram has been recommended; Due to risk of gallbladder complications, radiologic screening has been recommended; Management guidlines include hip and spine imaging to screen for hip dysplasia and cervical spine instability; Due to risk of glaucoma, ophthalmologic screening and management has been recommended; As neurological complications have been described, urgent brain imaging has been recommended in the setting of acute neurologic changes 14476546; 11737681; 12757706; 12757705; 17657823; 18509892; 19066960; 19697114; 21224894; 29397290 SUMO1 12502 7341 Orofacial cleft 10 AD N/A N/A Craniofacial General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16990542 SUN5 16252 140732 Spermatogenic failure 16 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27640305 SUOX 11460 6821 Sulfite oxidase deficiency AR Pediatric Biochemical; Neurologic; Ophthalmologic Biochemical Dietary measures (eg, low protein diet and synthetic amino acid mixture without cystine or methionine) have been described as beneficial in early reports 302914; 509724; 9428520; 10682307; 15952210; 12368985; 19793632 SURF1 11474 6834 Charcot-Marie-Tooth disease type 4K; Mitochondrial complex IV deficiency, nuclear type 1 AR N/A N/A Biochemical; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9837813; 9843204; 10443880; 10556302; 10746561; 11317352; 11804207; 12538779; 14557577; 15214016; 16326995; 17908801; 18583168; 19780766; 21937992; 24027061 SUZ12 17101 23512 Imagawa-Matsumoto syndrome AD N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28229514; 30019515; 31736240 SVBP 29204 374969 Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30607023 SVIL 11480 6840 Myofibrillar myopathy 10 AR Pediatric Cardiovascular; Musculoskeletal Cardiovascular The condition can involve cardiovascular sequelae, including ventricular hypertrophy with EKG abnormalities, and elevated cardiac enzymes, and awareness may allow early diagnosis and management 32779703 SYCE1 28852 93426 Premature ovarian failure 12 AR Pediatric Allelic with Spermatogenic failure 15 (AR) Endocrine; Genitourinary; Obstetric Endocrine; Obstetric The condition can include primary amenorrhea, and hormone therapy has been described as beneficial related to sexual development; Assistive reproductive technologies may be benefiical related to reproduction 25062452; 25899990; 26203179 SYCP2 11490 10388 Spermatogenic failure 1 AD N/A N/A Endocrine; Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31866047 SYCP3 18130 50511 Spermatogenic failure 4; Pregnancy loss, recurrent, 4 AD N/A N/A Genitourinary; Obstetric General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14643120; 19110213 SYN1 11494 6853 Epilepsy, X-linked, with variable learning disabilities and behavior disorders; Intellectual developmental disorder, X-linked 50 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14985377; 28973667 SYNE1 17089 23345 Emery-Dreifuss muscular dystrophy 4, autosomal dominant AD Pediatric Allelic with Arthrogryposis multiplex congenita 3, myogenic type (AR); Spinocerebellar ataxia, autosomal recessive 8 (AR) Cardiovascular; Musculoskeletal; Neurologic Cardiovascular One reported patient was found to have left ventricular basal and septal hypertrophy with mild diastolic dysfunction, and surveillance (eg, with echocardiogram) may allow early medical management 17503513; 17159980; 17761684; 19542096; 20301553; 20301609; 24319099; 27782104 SYNE2 17084 23224 Emery-Dreifuss muscular dystrophy 5, autosomal dominant AD Pediatric Cardiovascular; Musculoskeletal Cardiovascular Reported patients had cardiac findings such as arrhythmia, left ventricular hypertrophy, and dilated cardiomyopathy, and surveillance may allow early diagnosis and treatment; Heart transplantation has been reported 17761684 SYNE4 26703 163183 Deafness, autosomal recessive, 76 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 23348741 SYNGAP1 11497 8831 Mental retardation, autosomal dominant 5 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19196676; 23020937 SYNJ1 11503 8867 Developmental and epileptic encephalopathy 53; Parkinson disease 20, early-onset AR Pediatric Allelic with Developmental and epileptic encephalopathy 53 (AR) Neurologic Neurologic For Parkinson disease 20, response to levodopa has been described 23804563; 23804577; 27435091 SYP 11506 6855 Mental retardation, X-linked 96 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19377476 SYT1 11509 6857 Baker-Gordon syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25705886; 30107533 SYT14 23143 255928 Spinocerebellar ataxia, autosomal recessive 11 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21835308 SYT2 11510 127833 Myasthenic syndrome, congenital 7, presynaptic AD N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25192047 SZT2 29040 23334 Developmental and epileptic encephalopathy 18 AR N/A N/A Craniofacial; Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21835308; 23932106 TAB2 17075 23118 While some reported cardiac malformations may be readily clinically ascertained, other reported types may be more subtle, and targeted surveillance (eg, with echocardiography and electrocardiography) for findings that have been reported as including bicuspid aortic valve and aortic dilatation, left ventricular outflow obstruction, subaortic stenosis, atrial fibrillation and other arrhythmias, may allow early medical and/or surgical management, which may decrease morbidity and mortality AD Pediatric Cardiovascular Cardiovascular While some reported cardiac malformations may be readily clinically ascertained, other reported types may be more subtle, and targeted surveillance (eg, with echocardiography and electrocardiography) for findings that have been reported as including bicuspid aortic valve and aortic dilatation, left ventricular outflow obstruction, subaortic stenosis, and atrial fibrillation, may allow early medical and/or surgical management, which may decrease morbidity and mortality 20493459; 26139517; 27452334; 28386937; 31250519; 31959127 TAC3 11521 6866 Hypogonadotropic hypogonadism AR Pediatric Endocrine General Hormonal treatment (eg, with chorionic gonadotropin) can induce and maintain secondary sex characteristics, and can allow reproduction Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19079066 TACO1 24316 51204 Mitochondrial complex IV deficiency, nuclear type 8 AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19503089 TACR3 11528 6870 Hypogonadotropic hypogonadism AR Pediatric Endocrine Endocrine In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required 19079066; 20301509 TACSTD2 11530 4070 Corneal dystrophy, gelatinous drop-like AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10192395; 12614764; 19693293; 20806038; 21541270 TAF1 11535 6872 Dystonia 3, torsion, X-linked; Mental retardation, X-linked, syndromic 33 XL Pediatric Allelic with Mental retardation, X-linked, syndromic 33 (XL) Craniofacial; Musculoskeletal; Neurologic Neurologic Dystonia 3, torsion, X-linked may be responsive to levodopa 15596620; 17273961; 26637982 TAF13 11546 6884 Mental retardation, autosomal recessive 60 AR N/A N/A Endocrine; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28257693 TAF2 11536 6873 Mental retardation, autosomal recessive 40 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21937992; 24084144 TAF4B 11538 6875 Spermatogenic failure 13 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24431330 TAF6 11540 6878 Alazami-Yuan syndrome AR N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25558065; 25574841 TAFAZZIN 11577 6901 Barth syndrome (3-Methylglutaconic aciduria, type II) XL Pediatric Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Cardiovascular Surveillance for cardiomyopathy and early medical treatment may reduce morbidity; in some individuals, early cardiac transplant may be necessary; Individuals can also have neutropenia, and prophylaxis against infections, with early and aggressive management of infections may be beneficial 6142097; 2372897; 1998334; 1719174; 8434619; 8487269; 7616547; 8630491; 9332651; 9382097; 9382096; 9345098; 11238270; 11735032; 12468278; 12032589; 15098233; 7394203; 19648820; 20301486; 20812380; 22410210; 21987083 TALDO1 11559 6888 Transaldolase deficiency AR Pediatric Biochemical; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Renal Biochemical; Pharmacogenomic The use of N--acetylcysteine therapy has been reported as beneficial related to at least laboratory-based parameters; Studies have suggested that individuals may be sensitive to acetaminophen therapy, and that this medication should be avoided due to the risk of toxicity 11283793; 15877206; 17095351; 19401148; 21119539; 23315216; 27130472; 29923087 TANC2 30212 26115 Intellectual developmental disorder with autistic features and language delay, with or without seizures AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23033978; 24463507; 31616000 TANGO2 25439 128989 Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MECRCN) AR Pediatric Biochemical; Cardiovascular; Endocrine; Musculoskeletal; Neurologic Biochemical; Cardiovascular; Musculoskeletal Individuals may have cardiac arrhythmias and acute episodes of rhabdomyolysis, as well as hypoglycemia and lactic acidemia, and awareness may allow prompt management 26805781; 26805782 TAP1 43 6890 Bare lymphocyte syndrome, type I AR Pediatric Allergy/Immunology/Infectious; Pulmonary Allergy/Immunology/Infectious; Pulmonary The condition has been reported as possibly related to increased risk of malignancy as well as infectious manifestations Individuals may manifest with frequent and severe infections (including early-onset severe bacterial infections), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; For pulmonary manifestations, treatment recommendations analogous to those in individuals cystic fibrosis have been recommended; Immunosuppressive therapy may be contraindicated 3891604; 10074495; 10074494; 10931128; 17498556; 17982230; 17315195; 18668571 TAP2 44 6891 Bare lymphocyte syndrome, type I AR Pediatric Allergy/Immunology/Infectious; Pulmonary Allergy/Immunology/Infectious; Pulmonary The condition has been reported as possibly related to increased risk of malignancy as well as infectious manifestations Individuals may manifest with frequent and severe infections (including early-onset severe bacterial infections), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; For pulmonary manifestations, treatment recommendations analogous to those in individuals cystic fibrosis have been recommended; Immunosuppressive therapy may be contraindicated 7517574; 10074495; 10931128; 12644316; 17879436; 17879452; 20083708 TAPBP 11566 6892 Bare lymphocyte syndrome, type I AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Although the described individual did not have the same types of infections as other individuals with TAP deficiency, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 10074495; 12149238 TARDBP 11571 23435 Amyotrophic lateral sclerosis 10, with or without frontotemporal dementia AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17036243; 18288693; 18309045; 18372902; 18396105; 18438952; 18779421; 19224587; 19350673; 19609911; 20697052; 21220647; 21956716; 22292843; 22398199; 22456481; 22539580; 22722621; 24300238 TARS1 11572 6897 Trichothiodystrophy 7, nonphotosensitive AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious The condition has been described as involve recurrent respiratory infections, and awareness may allow prompt diagnosis and management of infections 31374204 TARS2 30740 80222 Combined oxidative phosphorylation deficiency 21 AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24827421 TAS2R16 14921 50833 Beta-glucopyranoside tasting AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16051168; 24177185 TAS2R38 9584 5726 Thiourea tasting; Phenylthiocarbamide tasting AD N/A N/A Neurologic General In Thiourea tasting; Phenylthiocarbamide tasting, the clinical applicability is unclear, though it has been suggested that variants may have health-related manifestations (eg, involving nicotine and alcohol use) 17830260; 12595690; 16086309; 17250611; 18524836; 22130969 TASP1 15859 55617 Suleiman-El-Hattab syndrome AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Among other features, individuals have been described with recurrent respiratory infections, and awareness may allow management of these sequelae 31209944 TAT 11573 6898 Tyrosinemia, type II AR Pediatric Biochemical; Dermatologic; Neurologic; Ophthalmologic Biochemical Dietary measures (controlled intake of phenylalanine and tyrosine) can be effective, including as relates to neurocognitive outcome 18901242; 33934; 6446465; 1356171; 1357662; 8912606; 12227462; 9544843; 16574453; 16917729; 18945316; 21145993; 21636300 TBC1D20 16133 128637 Warburg micro syndrome 4 AR N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24239381 TBC1D23 25622 55773 Pontocerebellar hypoplasia, type 11 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28823706; 28823707 TBC1D24 29203 57465 Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome; Deafness, autosomal recessive 86 AD/AR Pediatric Allelic with Deafness, autosomal dominant, 65 (AD); Myoclonic epilepsy, infantile, familial (AR); Developmental and epileptic encephalopathy16 (AR); Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp (AR) Audiologic/Otolaryngologic; Dermatologic; Musculoskeletal; Neurologic Audiologic/Otolaryngologic As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 10741954; 20797691; 20727515; 21087195; 22211675; 23343562; 23526554; 24291220; 24387994; 24729539; 24729547; 31257402 TBC1D2B 29183 23102 Neurodevelopmental disorder with seizures and gingival overgrowth AR N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32623794 TBC1D4 19165 9882 Diabetes mellitus, noninsulin-dependent 5 AR N/A N/A Endocrine General Heterozygous carriers may also display mild effects related to glucose metabolism Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25043022 TBC1D7 21066 51256 Macrocephaly/megalencephaly syndrome, autosomal recessive AR N/A N/A Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23687350; 24515783 TBC1D8B 24715 54885 Nephrotic syndrome, type 20 XL N/A N/A Renal General Renal transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30661770 TBCD 11581 6904 Early-onset progressive encephalopathy with brain atrophy and thin corpus callosum (PEBAT) AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27666370; 27666374 TBCE 11582 6905 Kenny-Caffey syndrome, type 1; Hypoparathyroidism-retardation-dysmorphism syndrome AR Pediatric Allelic with Progressive encephalopathy with amyotrophy and optic atrophy (PEAMO) (AR) Endocrine; Musculoskeletal; Neurologic; Ophthalmologic Endocrine Individuals can present with sequelae of neonatal hypocalcemia, and prompt diagnosis and treatment can lead to correction of electrolyte abnormalities; Some individuals with multiple pituitary anomalies (eg, affecting GH, cortisol, and including features of hypogonadotropic hypogonadism have been described), and surveillance may allow early diagnosis and treatment 2843457; 1701077; 2001103; 1308349; 7538982; 9056548; 12389028; 19491227; 19554981; 27666369 TBCK 28261 93627 Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25558065; 27040691; 27040692 TBK1 11584 29110 Encephalopathy, acute, infection-induceed (herpes-specific), susceptibility to, 8 AD Pediatric Allelic with Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (AD) Allergy/Immunology/Infectious; Neurologic Allergy/Immunology/Infectious Individuals may be susceptible to severe herpes simplex virus infections including herpes encephalitis has been described, and awareness may allow early diagnosis and treatment, potentially decreasing morbidity and mortality 22851595; 25803835; 25943890 TBL1X 11585 6907 Hypothyroidism, congenital, nongoitrous, 8 XL Pediatric Audiologic/Otolaryngologic; Endocrine Audiologic/Otolaryngologic; Endocrine Individuals may have hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with hypothyroidism, and awareness may allow management (eg, with thyroid hormone replacement) 27603907; 30591955 TBL1XR1 29529 79718 Mental retardation, autosomal dominant 41; Pierpont syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9450851; 16007632; 22495309; 23160955; 24891185; 25102098; 26769062 TBL1Y 18502 90665 Deafness, Y-linked 2 YL N/A N/A Audiologic/Otolaryngologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30341416 TBP 11588 6908 Spinocerebellar ataxia 17 AD/AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10484774; 11448935; 11313753; 11914409; 11939898; 12805114; 15521976; 14985389; 15313853; 15365789; 20587494; 21108634; 21710129 TBR1 11590 10716 Intellectual developmental disorder with autism and speech delay AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25232744; 29288087; 30250039; 30268909 TBX1 11592 6899 Conotruncal anomaly face syndrome; Tetralogy of Fallot AD N/A N/A Cardiovascular; Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14585638; 16684884; 17273972; 17377518; 19948535; 20937753 TBX15 11594 6913 Cousin syndrome AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7103674; 19068278 TBX18 11595 9096 Congenital anomalies of the kidney and urinary tract 2 AD Pediatric Renal Renal Renal transplantation has been described Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function 26235987 TBX19 11596 9095 Adrenocorticotropic hormone deficiency AR Pediatric Endocrine Endocrine Individuals may have severe neonatal hypoglycemia, and treatment of adrenocortical insufficiency (eg, with hydrocortisone, fludricortisone) can be effective 4295129; 6314808; 2830787; 8222301; 11290323; 15613420 TBX2 11597 6909 Vertebral anomalies and variable endocrine and T-cell dysfunction AD Pediatric Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Endocrine; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Endocrine The condition can include endocrine dysfunction, and awareness may allow prompt diagnosis and management; Immune deficiency has been described, and awareness may allow preventative measures and prompt treatment of infections 29726930 TBX20 11598 57057 Atrial septal defect 4 AD Pediatric Cardiovascular Cardiovascular Variants can result in a wide spectrum of cardiac-related disease, some of which may be challenging to recognize, and awareness may allow early medical and/or surgical management of manifestations, which can include valvular disease and cardiomyopathy in addition to frank structural anomalies such as ASD 17668378; 19762328 TBX22 11600 50945 Cleft palate with or without ankyloglossia XL N/A N/A Craniofacial General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11559848; 12374769; 14729838; 15602089; 17846996; 17868388; 21248356; 22784330 TBX3 11602 6926 Ulnar-Mammary syndrome AD N/A N/A Cardiovascular; Dental; Endocrine; Genitourinary; Musculoskeletal; Renal Cardiovascular The condition can involve multiple congenital anomalies Cardiac anomalies, including arrhythmias, have been reported, and surveillance may allow early detection and management 9207801; 12116211; 12668170; 19938096; 21199695; 28145909 TBX4 11603 9496 Ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension AD Pediatric Allelic with Amelia, posterior, with pelvic and pulmonary hypoplasia syndrome (AR) Cardiovascular; Genitourinary; Musculoskeletal; Neurologic; Pulmonary Cardiovascular; Pulmonary The condition can include pulmonary artery hypertension, and awareness may allow prompt diagnosis and management 15106123; 23592887; 30413314; 31151956; 31761294 TBX5 11604 6910 Holt-Oram syndrome AD Pediatric Cardiovascular; Musculoskeletal Cardiovascular While the condition may be recognizable in the majority, individuals may have cardiac conduction abnormalities even without known cardiac malformations, and surveillance (eg, with electrocardiography) may allow early detection and management 14402857; 8730285; 8911604; 8988165; 8988164; 10077612; 10842287; 12818525; 17366586; 18818409; 20301290 TBX6 11605 6911 Spondylocostal dysostosis 5 AD/AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23335591; 25564734; 28054739; 31015262 TBXA2R 11608 6915 Bleeding disorder, platelet-type 13, susceptibility to AD Pediatric Hematologic Hematologic; Pharmacogenomic Heterozygosity may cause abnormal in vitro platelet functional responses, but do not cause in vivo clinically significant dysfunction; Susceptibility is inherited in an autosomal dominant pattern, but clinical features, including mild mucocutaneous bleeding, occur only in the presence of a 'second hit' affecting platelet function Surveillance and prompt treatment of bleeding diatheses may be beneficial; Avoidance of agents that may provoke or worsen bleeding episodes is warranted 7929844; 19828703; 21070398; 22101342 TBXAS1 11609 6916 Ghosal hematodiaphyseal syndrome AR Pediatric Hematologic; Musculoskeletal; Neurologic Hematologic Steroid therapy has been described as effective for some hematologic manifestations 3385529; 2715908; 8444247; 17203301; 18264100 TBXT 11515 6862 Chordoma AD Pediatric Allelic with Sacral agenesis with vertebral anomalies (AR) Gastrointestinal; Musculoskeletal; Oncologic; Renal Oncologic Variants include duplications, and certain SNPs may confer a relatively high odds ratio; Sacral agenesis with vertebral anomalies can involve multiple congenital anomalies Surveillance for neoplasms could potentially be beneficial in order to allow early detection and treatment 8733136; 10204846; 10332959; 10817656; 12116228; 15449172; 19801981; 23064415; 24253444 TCAP 11610 8557 Cardiomyopathy, dilated, 1N; Cardiomyopathy, familial hypertrophic 25; Muscular dystrophy, limb-girdle, autosomal recessive 7 AD/AR Pediatric Cardiovascular; Musculoskeletal Cardiovascular The reported onset of heart failure has been in the adult period (including in young adults), but surveillance and early treatment may be indicated prior to adulthood; A variant has been described in an individual with intestinal pseudo-obstruction, but it is not clear if early (genetic) diagnosis would be beneficial Surveillance (eg, with echocardiography/electrocardiography) and preventive management may ameliorate/prevent severe sequelae 9245996; 10655062; 12507422; 15582318; 16352453; 16650785; 16490376; 19412328; 18408010; 22029105; 21530252 TCF12 11623 6938 Craniosynostosis 3 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23354436 TCF20 11631 6942 Developmental delay with variable intellectual impairment and behavioral abnormalities AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25228304; 27436265; 28135719; 30739909; 30819258 TCF3 11633 6929 Agammaglobulinemia 8, autosomal dominant AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described with severe and recurrent infrections, and awareness may allow prompt diagnosis and early and aggressive treatment of infections 24216514 TCF4 11634 6925 Corneal dystrophy, Fuchs endothelial, 3; Pitt-Hopkins syndrome AD N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 728011; 17436254; 17478476; 17436255; 18728071; 19235238; 19938247; 22045651; 24255041; 25593321; 25722209 TCHH 11791 7062 Uncombable hair syndrome 3 AR N/A N/A Dermatologic General The clinical relevance of the condition is unclear 27866708 TCIRG1 11647 10312 Osteopetrosis, autosomal recessive 1 AR Pediatric Audiologic/Otolaryngologic; Dental; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Hematologic; Musculoskeletal Milder forms of disease, possibly due to heterozygous variants have been described Although the disorder may be frequently recognizable, medical treatments (eg, calcitriol, interferon gamma-1b) as well as surgical interventions may be beneficial; Early and aggressive treatment of infectious and hematologic manifestations, as well as neonatal hypocalcemia, which can result in tetanic seizures, may be beneficial; Awareness of multi-organ system complications may allow surveillance and prompt interventions; BMT/HSCT has been described 13532685; 4170880; 6986555; 6546410; 2877234; 1320672; 8291528; 7996361; 7753137; 10888887; 10942435; 12566520; 20870624; 20424301; 21042819; 23329773; 23412864 TCN2 11653 6948 Transcobalamin II deficiency AR Pediatric Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Hematologic; Neurologic Allergy/Immunology/Infectious; Biochemical The condition can include neurocognitive impairment, hematologic anomalies (eg, anemia, panyctopenia), susceptibility to recurrent and severe infections, and gastrointestinal sequelae, and cobalamin treatment can result in prevention and/or clinical improvement, including related to developmental parameters; Awareness of immunodeficiency may allow prompt treatment of infections 5096637; 4138209; 128427; 3143215; 309761; 1743216; 7849710; 19373259 TCOF1 11654 6949 Treacher Collins syndrome 1 AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Ophthalmologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 8563749; 8875242; 8894686; 9042910; 9096354; 11013442; 14598341; 15150774; 15214011; 15340364; 19050407; 19067896; 19572402; 20301704; 22317976; 22729243; 25790162 TCTN1 26113 79600 Joubert syndrome 13 AR N/A N/A Musculoskeletal; Neurologic General The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20301500; 21725307; 26477546 TCTN2 25774 79867 Joubert syndrome 24; Meckel syndrome 8 AR N/A N/A Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Renal General The conditions may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveilMMABlance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20301500; 21462283; 21565611; 25118024 TCTN3 24519 26123 Joubert syndrome 18; Orofaciodigital syndrome IV (Mohr-Majewski syndrome) AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal General The condition can include cardiac, renal, and other manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22883145 TDGF1 11701 6997 Forebrain anomalies; Congenital cardiac malformations AD N/A N/A Craniofacial; Cardiovascular; Endocrine; Neurologic General Individuals with forebrain anomalies such as holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12073012; 18538293 TDO2 11708 6999 Hypertryptophanemia AD N/A N/A Biochemical General The clinical relevance of the condition is unclear 28285122 TDP1 18884 55775 Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12244316 TDP2 17768 51567 Spinocerebellar ataxia, autosomal recessive 23 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24658003 TDRD7 30831 23424 Cataract 36 AR Pediatric Ophthalmologic Ophthalmologic; Pharmacogenomic Some affected individuals have been described as developing open-angle glaucoma with increased intraocular pressure following cataract extraction; Agents that may contribute to glaucoma should be avoided 21436445 TDRD9 20122 122402 Spermatogenic failure 30 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28536242 TEAD1 11714 7003 Sveinsson choreoretinal atrophy AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15016762 TECPR2 19957 9895 Spastic paraplegia 49, autosomal recessive AR N/A N/A Craniofacial; Gastrointestinal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23176824 TECR 4551 9524 Mental retardation, autosomal recessive 14 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11590547; 18446860; 21212097 TECRL 27365 253017 Ventricular tachycardia, catecholaminergic polymorphic, 3 AR Pediatric Cardiovascular Cardiovascular The condition can include cardiac arrest and sudden cardiac death, and medical and surgical interventions (eg, with ICD) has been described as beneficial 17666061; 27861123 TECTA 11720 7007 Deafness, autosomal recessive 21; Deafness, autosomal dominant 8/12 AD/AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 9150164; 9718342; 9763681; 10987647; 9590290; 9949200; 11333869; 12746400; 17661817; 17431902; 23226338 TEK 11724 7010 Glaucoma 3, primary congenital, E; Venous malformations, multiple cutaneous and mucosal AD Pediatric Cardiovascular; Ophthalmologic Cardiovascular; Ophthalmologic In Glaucoma 3, primary congenital, E, individuals can have infant/early-childhood ocular hypertension, and optic neuropathy, resulting in vision loss, aand awareness may allow early diagnosis, surveillance, and management; In Venous malformations, multiple cutaneous and mucosal, some individuals have venous malformations (including vascular neoplasms) within internal organs that could lead to severe sequelae, and cardiac malformations have also been described in a few individuals 7833915; 7783168; 8980225; 10369874; 19888299; 27270174 TELO2 29099 9894 You-Hoover-Fong syndrome AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27132593 TENM1 8117 10178 Microphthalmia, isolated, with coloboma 9 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22766609 TENM3 29944 55714 Microphthalmia, isolated, with coloboma 9 AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22766609; 29753094; 30513139 TENM4 29945 26011 Tremor, hereditary essential, 5 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26188006 TENT5A 18345 55603 Osteogenesis imperfecta, type XVIII AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29358272 TERC 11727 7012 Dyskeratosis congenita, autosomal dominant 1; Aplastic anemia; Pulmonary fibrosis and/or bone marrow failure, telomere-related 2 AD Pediatric Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic; Oncologic; Pulmonary Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary The presence of variants has also been reported as increasing risk of malignancy, including melanoma In dyskeratosis congenita, the presentation many not always be classic, and individuals are at high risk for hematologic anomalies (including bone marrow failure) and malignancy, and surveillance and prompt diagnosis and treatment may be beneficial; In Aplastic anemia, surveillance and prompt treatment of aplastic anemia and bone marrow failure may reduce morbidity; For treatment related to pulmonary fibrosis, immunotherapy may be beneficial, though lung transplantation may be indicated in individuals with severe/refractory disease 11574891; 12090986; 14630445; 17392301; 18753630; 19760749; 21436073; 22341970; 20301779; 23348503 TERT 11730 7015 Aplastic anemia; Dyskeratosis congenita, autosomal dominant; Dyskeratosis congenita, autosomal recessive; Pulmonary fibrosis and/or bone marrow failure, telomere-related 1 AD/AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Dental; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Pulmonary Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary In dyskeratosis congenita, the presentation many not always be classic, and individuals are at high risk for hematologic anomalies (including bone marrow failure) and malignancy, and surveillance and prompt diagnosis and treatment may be beneficial; In Aplastic anemia, surveillance and prompt treatment of aplastic anemia and bone marrow failure may reduce morbidity; HSCT may be effective; For treatment related to pulmonary fibrosis, immunotherapy may be beneficial, though lung transplantation may be indicated in individuals with severe/refractory disease 16247010; 15814878; 16890917; 17392301; 17785587; 17460043; 18460650; 18042801; 19760749; 21602826; 20502709; 21436073; 22512499; 20301779 TET2 25941 54790 Immunodeficiency 75 AR Pediatric Allergy/Immunology/Infectious; Neurologic; Oncologic Allergy/Immunology/Infectious; Oncologic Individuals have been described with severe and early-onset infections, and awareness may allow early and aggressive management of infections; The condition can include hematologic malignancies, and awareness may allow early diagnosis and management; HSCT has been described 32518946 TET3 28313 200424 Beck-Fahrner syndrome AD/AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31928709 TEX11 11733 56159 Spermatogenic failure, X-linked 2 XL N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25970010 TEX14 11737 56155 Spermatogenic failure 23 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28206990 TEX15 11738 56154 Spermatogenic failure 25 AR N/A N/A Endocrine; Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26199321; 28303806; 28355598 TF 11740 7018 Atransferrinemia AR Pediatric Hematologic Hematologic The condition, which involves microcytic anemia and iron overload, can have insidious, nonspecific, and severe manifestations that may include congestive heart failure, and treatment with plasma infusion has been described as effective 13906010; 4625559; 8317485; 11110675; 15466165; 18097132; 19579082 TFAM 11741 7019 Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) AR N/A N/A Biochemical; Gastrointestinal; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27448789 TFAP2A 11742 7020 Branchiooculofacial sydrome AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic Audiologic/Otolaryngologic The condition may be recognizable due to the presence of a specific pattern of congenital malformations affecting hearing as well as multiple organ systems; An individual with medulloblastoma has been described Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 1619642; 7747785; 9761567; 18423521; 19685247; 19764023; 19206157; 20358615; 20635357; 21634087; 21204207 TFAP2B 11743 7021 Char syndrome; Patent ductus arteriosus 2 AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 728571; 1342853; 8326495; 7645594; 9217229; 10368122; 10802654; 10955477; 11102923; 11505339; 15684060; 18752453; 21643846 TFG 11758 10342 Neuropathy, hereditary motor and sensory, Okinawa type; Spastic paraplegia 57 AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17906970; 22883144; 23479643; 23553329; 25098539 TFR2 11762 7036 Variants may also modify hemochromatosis due to variants in other genes (eg, HFE) AR Pediatric Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic Biochemical; Gastrointestinal; Hematologic Variants may also modify hemochromatosis due to mutations in other genes (eg, HFE) Preventive measures and treatment of iron overload (by phlebotomy) can be beneficial 10216143; 10802645; 12150153; 12130528; 19549277; 20542038; 21770687 TFRC 11763 7037 Immunodeficiency 46 AR Pediatric Allergy/Immunology/Infectious; Hematologic Allergy/Immunology/Infectious The condition has been described as involving severe childhood-onset infections, and and awareness may allow preventive measures, and early and aggressive treatment of infections; HSCT has been described 26642240 TG 11764 7038 Thyroid dyshormonogenesis 3 AR Pediatric Endocrine; Oncologic Endocrine; Oncologic Medical treatment of hypothyroidism (eg, with T4) can be effective ; Thyroid neoplasms have also been reported, and surveillance may be beneficial to allow early treatment 2584351; 1752952; 14657345; 14557492; 14764776; 16187918; 16403815; 16720658; 16477365; 17244789 TGDS 20324 23483 Catel-Manzke syndrome AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6011685; 9777339; 18501694; 22887726; 25480037 TGFB1 11766 7040 Camurati-Engelmann disease; Inflammatory bowel disease, immunodeficiency, and encephalopathy AD/AR Pediatric Allergy/Immunology/Infectious; Hematologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Musculoskeletal In Camurati-Engelmann disease, medical management (eg, corticosteroids and/or losartan) may be beneficial to help with many manifestations, including pain, gait disturbances, anemia, hepatosplenomegaly, and exercise intolerance; In Inflammatory bowel disease, immunodeficiency, and encephalopathy, individuals have been reported with recurrent infections and immunologic manifestations affecting multiple organ systems, and awareness may allow management related to these sequelae 5503688; 4461085; 7298693; 9054935; 11062463; 10973241; 11810278; 21462384; 12493741; 15326622; 15894597; 20301335; 29483653 TGFB2 11768 7042 Loeys-Dietz syndrome, type 4 AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal Cardiovascular Though manifestations may occur primarily in adults, surveillance in the pediatric period may be indicated Individuals may manifest with cardiovascular anomalies, including thoracic aortic aneurysm as well as cardiac valvular anomalies, and awareness may allow early diagnosis and preventive measures and medical management in order to decrease morbidity and mortality 20301312; 22772371; 22772368 TGFB3 11769 7043 Arrhythmogenic right ventricular dysplasia 1; Loeys-Dietz syndrome 5 (Reinhoff syndrome) AD Pediatric Cardiovascular; Craniofacial; Musculoskeletal Cardiovascular Individuals with Arrhythmogenic right ventricular dysplasia may manifest with syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation; Individuals with Loeys-Dietz syndrome 5 (Reinhoff syndrome) have been described with cardiovascular anomalies including structural abnormalities and aortic aneurysms as well as arrhythmia, and awareness may allow early management 1572740; 12529708; 15639475; 19362677; 20301310; 23824657; 24798638; 25835445 TGFBI 11771 7045 Corneal dystrophy, lattice type I; Corneal dystrophy, lattice type IIIA; Corneal dystrophy of Bowman layer, type I; Corneal dystrophy, Avellino type; Corneal dystrophy, Reis-Bucklers type; Corneal dystrophy, Thiel-Behnke type; Corneal dystrophy, Groenouw type I; Corneal dystrophy, epithelial basement membrane AD N/A N/A Ophthalmologic General It has been reported that in affected individuals with CDA, LASIK can increase the deposition of visually significant corneal opacities; Corneal epithelial debridement and fibronectin eye drops has been described as potentially delaying the need for keratoplasty or phototherapeutic keratoplasty; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9780098; 9727509; 9497262; 10442892; 11867580; 11923233; 15531312; 15019320; 15885785; 15111592; 15790870; 16652336; 16606891; 22080335; 22155582; 22194646; 22355247; 22575726 TGFBR1 11772 7046 Loeys-Dietz syndrome, type 1A; Loeys-Dietz syndrome, type 2A AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Obstetric Cardiovascular; Obstetric Medical management to decrease risk of vascular events is warranted, including avoidance of certain types of activities such as contact sports; Specific surveillance for surgical considerations related to issues such as aneurysms and cervical spine instability, other issues include subacute bacterial endocarditis prophylaxis with dental work; Precautions during pregnancy may be warranted due to the potential of complications including uterine rupture 5173258; 3565476; 15731757; 16928994; 20301312; 19542084; 21358634; 24344637 TGFBR2 11773 7048 Loeys-Dietz syndrome, type 2 AD Pediatric Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Obstetric Cardiovascular; Obstetric An increased risk of colorectal cancer has been reported Medical management to decrease risk of vascular events is warranted, including avoidance of certain types of activities such as contact sports; Specific surveillance for surgical considerations related to issues such as aneurysms and cervical spine instability, other issues include subacute bacterial endocarditis prophylaxis with dental work; Precautions during pregnancy may be warranted due to the potential of complications including uterine rupture 15235604; 16027248; 15731757; 16928994; 16251899; 19006214; 19542084; 19996017; 24344637 TGIF1 11776 7050 Holoprosencephaly 4 AD N/A N/A Craniofacial; Endocrine; Neurologic General Individuals with holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10835638; 16199538; 20104608; 22125506; 21940735 TGM1 11777 7051 Ichthyosis, congenital, autosomal recessive 1 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7977373; 7824952; 7773290; 9326318; 9545389; 12542526; 18948357; 19486042; 19556108; 19863506; 20064174; 20301593; 22435431 TGM3 11779 7053 Uncombable hair syndrome 2 AR N/A N/A Dermatologic General The clinical relevance of the condition is unclear 27866708 TGM5 11781 9333 Peeling skin syndrome 2 AR N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16380904 TGM6 16255 343641 Spinocerebellar ataxia 35 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21106500; 22554020 TH 11782 7054 Segawa syndrome, autosomal recessive AR Pediatric Biochemical; Neurologic Biochemical The condition can have infantile onset, and treatment (eg, with L-dopa alone or combined with other medications), can be effective, though has not been reported to be universally so 7814018; 8817341; 9732974; 10407773; 10585338; 11196107; 16049992; 17696123; 10753262; 11246459; 11241071; 11134401; 11921123; 12891655; 14705130; 15505183; 18058633; 19282209; 20056467; 20301610; 21937992; 21940685; 22264700; 22691284; 22815559; 23389938 THAP1 20856 55145 Dystonia 6, torsion AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9382482; 17702011; 19345147; 19345148; 19182804; 20211909; 20083799; 21520283; 21793105; 21839475; 21847143; 21949105; 22377579 THBD 11784 7056 Thrombophilia due to thrombomodulin defect; Hemolytic uremic syndrome, atypical, susceptibility to, 6 AD Pediatric (Hemolytic uremic syndrome, atypical, susceptibility to, 6); Adult (Thrombophilia due to thrombomodulin defect) Hematologic; Renal Hematologic; Pharmacogenomic; Renal The evidence for the causality of the reported variants as relates to thrombophilia is unclear In Thrombophilia due to thrombomodulin defect, surveillance, preventive measures, and treatment of thrombophilia may reduce morbidity; In Hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications) 7811989; 9843165; 10460600; 11552992; 12139752; 11986219; 19625716; 20301541; 20595690; 22036808 THG1L 26053 54974 Spinocerebellar ataxia, autosomal recessive 28 AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27307223; 30214071; 31168944 THOC2 19073 57187 Mental retardation, X-linked 12 XL N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26166480 THOC6 28369 79228 Beaulieu-Boycott-Innes syndrome AR N/A N/A Cardiovascular; Craniofacial; Dental; Genitourinary; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23621916; 26739162; 27102954; 30476144 THPO 11795 7066 Thrombocythemia 1 AD Pediatric Hematologic; Oncologic Hematologic; Oncologic Individuals may have hemorrhagic or thrombotic tendencies, and preventive measures and prompt treatment may be beneficial; Surveillance for and early treatment of oncologic complications may also be beneficial 8167182; 7772529; 9425899; 10583217; 18367486; 22453305 THRA 11796 7067 Hypothyroidism, congenital, nongoitrous, 6 AD Pediatric Endocrine Endocrine Thyroid replacement therapy has been reported as beneficial in some described individuals 22168587; 25670821 THRB 11799 7068 Thyroid hormone resistance, generalized, autosomal dominant; Thyroid hormone resistance, selective pituitary; Thyroid hormone resistance, generalized, autosomal recessive AD/AR Pediatric Endocrine Endocrine In Thyroid hormone resistance, generalized, unhelpful, potentially invasive treatment regimens that may involve adverse effects may be avoided with efficient (genetic) diagnosis, and medical treatment (eg, with types of triiodothyroacetic acid) may be beneficial related to biological parameters as well as sequelae affecting multiple systems, such as the cardiovascular and neurologic systems; In Thyroid hormone resistance, selective pituitary, affected individuals may more frequently benefit from efforts to lower serum thyroid hormone concentration 4163616; 1159077; 6792914; 6287848; 3571851; 2510172; 2153155; 1991834; 1653889; 8381821; 8450877; 1400869; 8384535; 8496318; 8040303; 15913586; 17596672; 19268523; 19378427; 20020587; 22319036; 22696245; 22947347; 23134553; 23633200 THSD1 17754 55901 Aneurysm, intracranial berry, 12 AD Adult Cardiovascular Cardiovascular Individuals have been described with intracranial aneurysms, some of which progressed to subarachnoid hemorrhage, and awareness may allow early diagnosis and managements 27895300 TIA1 11802 7072 Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia; Welander distal myopathy AD N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23348830; 28817800; 29216908 TICAM1 18348 148022 Encephalopathy, acute, infection-induceed (herpes-specific), susceptibility to, 6 AD/AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be susceptible to severe herpes simplex virus infections (eg, herpes encephalitis), and awareness may allow early diagnosis and treatment (eg, with acyclovir, which has been reported as effective reported individuals), potentially decreasing morbidity and mortality 22105173 TIMM22 17317 29928 Combined oxidative phosphorylation deficiency 43 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30452684 TIMM50 23656 92609 3-methylglutaconic aciduria, type IX AR Pediatric Biochemical; Neurologic; Ophthalmologic Neurologic The condition can include seizures, and there is a report of specific medical management (with vigabatrin) conferring benefit 27573165; 32369862 TIMM8A 11817 1678 Opticoacoustic nerve atrophy with dementia; Jensen syndrome; Mohr-Tranebjaerg syndrome XL Pediatric Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Ophthalmologic Audiologic/Otolaryngologic; Pharmacogenomic Deafness may be postlingual in many individuals with certain TIMM8A-related conditions Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Aminoglycosides should be avoided 5649; 7643352; 8841189; 10878669; 11803487; 11405816; 18952432 TIMMDC1 1321 51300 Mitochondrial complex I deficiency, nuclear type 31 AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28604674 TIMP3 11822 7078 Sorsby fundus dystrophy AD N/A N/A Ophthalmologic General Vitamin A administration in early disease stages may postively affect manifestations such as night blindness, but long term efficacy is unclear; Antioangiogenic agents have been suggested as possibly beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18111349; 7148944; 7894485; 7550309; 8981947; 18501328 TINF2 11824 26277 Dyskeratosis congenita, autosomal dominant 3; Revesz syndrome AD Pediatric Allergy/Immunology/Infectious; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Pulmonary Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; Lung transplant may be indicated in individuals with advanced lung diease; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal; Awareness of infectious risk may allow prompt diagnosis and treatment of infections 1404302; 18252230; 18669893; 20301779; 21199492 TJP2 11828 9414 Hypercholanemia, familial; Cholestasis, progressive familial intrahepatic 4 AR Pediatric Allelic with Deafness, autosomal dominant 51 (AD), which has been reported as due to genomic duplications Audiologic/Otolaryngologic; Gastrointestinal; Oncologic Gastrointestinal; Oncologic Deafness, autosomal dominant 51 has been reported as due to genomic duplications, though evidence for causation of other variants appears to be unclear In Hypercholanemia, Individuals may present with findings such as fat malabsorption, with consequent failure to thrive, coagulopathy, and rickets, and typically respond to medical treatment (eg, with ursodeoxycholic acid); In Familial intrahepatic cholestasis, medical treatment (eg, with ursodeoxycholine) may be beneficial, though liver transplantation has been described as necessary in some individuals; Medications (eg, OCPs) may lead to adverse reactions; In pregnancy, the condition can cause severe sequelae (including death) in the fetus, as well as adverse maternal health outcomes, and precautions, including early delivery, may be beneficial; Individuals have been reported with hepatocellular carcnioma, and awareness may allow early diagnosis and management 12704386; 20602916; 24614073; 25921221 TK2 11831 7084 Mitochondrial DNA depletion syndrome 2; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 AR N/A N/A Biochemical; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1734306; 11687801; 12391347; 18819985; 19125351; 19736010; 19815440; 20421844; 21937588; 22345218 TKFC 24552 26007 Triokinase and FMN cyclase deficiency syndrome AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32004446 TKT 11834 7086 Short stature, developmental delay, and congenital heart defects AR N/A N/A Cardiovascular; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27259054 TLE6 30788 79816 Preimplantation embryonic lethality 1 AR N/A N/A Obstetric General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26537248 TLK2 11842 11011 Mental retardation, autosomal dominant 57 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27479843; 29861108 TLL1 11843 7092 Atrial septal defect 6 AD Pediatric Cardiovascular Cardiovascular The condition can include arrhthymias as well as frank congenital cardiac malformations In addition to managing congenital cardiac malformations, surveillance for (eg, including electrocardiogram) and treatment of accompanying arrhythmias may be effective 18830233 TLR3 11849 7098 Herpes simplex encephalitis, susceptibility to, 2 AD/AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be susceptible to HSV (though not other) infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 17872438; 21911422 TLR7 15631 51284 Immunodeficiency 74, COVID-19 related, X-linked XL Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may demonstrate susceptibility to severe COVID-19, and awareness may allow preventative measures (such as adhering to practices to reduce the chance of infection) 32706371 TM4SF20 26230 79853 Specific language impairment 5 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23810381 TMC1 16513 117531 Deafness, autosomal recessive 7 AR Pediatric Allelic with Deafness, autosomal dominant 36 (AD) Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 11850618; 17250663; 18616530; 23226338; 24827932 TMC6 18021 11322 Epidermodysplasia verruciformis, susceptibility to, 1 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Oncologic Oncologic Individuals are at high-risk of developing skin cancers, and surveillance may be beneficial to allow early detection and treatment 10084299; 10844558; 12426567 TMC8 20474 147138 Epidermodysplasia verruciformis, susceptibility to, 2 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Oncologic Oncologic Individuals are at high-risk of developing skin cancers, and surveillance may be beneficial to allow early detection and treatment 10084299; 10844558; 12426567 TMCO1 18188 54499 Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome AR Pediatric Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal Renal The condition can involve multiple congenital anomalies Individuals have been described with renal anomalies and/or vesicoureteral reflux, and surveillance and management may be helpful to preserve renal function 17351359; 20018682; 23320496; 24194475; 30556256; 31102500 TMEM106B 22407 54664 Leukodystrophy, hypomyelinating 16 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29186371; 29444210 TMEM107 28128 84314 Joubert syndrome 29; Meckel syndrome 13; Orofaciodigital syndrome XVI AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26123494; 26518474; 26595381 TMEM126A 25382 84233 Optic atrophy 7 with or without auditory neuropathy AR N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Neurologic; Ophthalmologic General One patient has been described as presenting with moderate hypertrophic cardiomyopathy; A heterozygote has been described as manifesting with transient loss of vision following exercise (Uhthoff's sign of optic neuropathy) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19327736; 20301500; 20405026; 22815638 TMEM126B 30883 55863 Mitochondrial complex I deficiency, nuclear type 29 AR Pediatric Biochemical; Cardiovascular; Musculoskeletal; Neurologic Cardiovascular Among other findings, individuals have been described with hypertrophic cardiomyopathy, and awareness may allow prompt diagnosis and management 27374773; 27374774 TMEM127 26038 55654 Pheochromocytoma AD Adult Oncologic Oncologic Although adults have been reported, surveillance in the pediatric period may nevertheless be warranted Surveillance and awareness of cancer risk may allow early diagnosis and treatment of neoplasms, which may reduce morbidity and mortality 20154675; 22419703; 23666964 TMEM132E 26991 124842 Deafness, autosomal recessive 99 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 25331638; 31656313 TMEM138 26944 51524 Joubert syndrome 16 AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22282472; 20301500 TMEM165 30760 55858 Congenital disorder of glycosylation, type IIk AR N/A N/A Biochemical; Craniofacial; Dental; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic General Hepatic-metabolized agents should be avoided Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 22683087; 23430531 TMEM199 18085 147007 Congenital disorder of glycosylation, type IIp AR Pediatric Biochemical; Gastrointestinal; Hematologic; Neurologic Hematologic Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery 26833330 TMEM216 25018 51259 Joubert syndrome 2; Meckel syndrome 2 AR N/A N/A Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Conditions may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20036350; 20512146 TMEM231 37234 79583 Joubert syndrome 20; Meckel syndrome 11 AR N/A N/A Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Conditions may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23012439; 23349226 TMEM237 14432 65062 Joubert syndrome 14 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17603801; 20301500; 22152675 TMEM240 25186 339453 Spinocerebellar ataxia 21 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11160961; 25070513 TMEM251 20218 26175 Dysostosis multiplex, Ain-Naz type AR N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33252156 TMEM260 20185 54916 Structural heart defects and renal anomalies syndrome (SHDRA) AR N/A N/A Cardiovascular; Neurologic; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28318500 TMEM38B 25535 55151 Osteogenesis imperfecta, type XIV AR N/A N/A Musculoskeletal General The use of bisphosphonates has been described in osteogenesis imperfecta, but it is unclear if an early (genomic) diagnosis would be advantageous Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23316006 TMEM43 28472 79188 Arrhythmogenic right ventricular dysplasia 5; Emery-Dreifuss muscular dystrophy 7, autosomal dominant AD Pediatric Cardiovascular; Musculoskeletal Cardiovascular Individuals may manifest with arrhythmias (which have been reported in multiple individuals with EDMD 7), syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantation 18313022; 20301310; 21391237 TMEM63A 29118 9725 Leukodystrophy, hypomyelinating, 19, transient infantile AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31587869 TMEM67 28396 91147 COACH syndrome AR Pediatric Allelic with Nephronophthisis 11 (AR); Meckel syndrome 3 (AR); Joubert syndrome 6 (AR); RHYNS syndrome (AR) Audiologic/Otolaryngologic; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal Gastrointestinal The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Variants may modify severity of BBS and related disorders due to variants in other BBS-associated genes; Renal transplant has been described in RHYNS syndrome In COACH syndrome, among other findings, individuals may have hepatic disease, and it has been suggested that identification of liver disease is critical as some patients may develop complications such as portal hypertension with fatal variceal bleeding 4688793; 9375913; 17160906; 18327255; 19058225; 19508969; 19574260; 20232449; 20607301; 21633164; 21068128; 29891882 TMEM70 26050 54968 Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 AR N/A N/A Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18953340; 21147908; 24485043 TMEM94 28983 9772 Intellectual developmental disorder with cardiac defects and dysmorphic facies AR N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30526868 TMEM98 24529 26022 Nanophthalmos 4 AD N/A N/A Ophthalmologic Ophthalmologic As the condition can include glaucoma, surveillance can allow early interventions that may potentially be beneficial related to preservation of visual status 24852644 TMIE 30800 259236 Deafness, autosomal recessive 6 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12145746; 19438934 TMLHE 18308 55217 Epsilon-trimethyllysine hydroxylase deficiency AD Pediatric Biochemical; Neurologic Biochemical The condition may be associated with autism, and carnitine supplementation has been reported as beneficial related to developmental milestones 21865298; 22566635; 25943046 TMPO 11875 7112 Cardiomyopathy, dilated, 1T AD Pediatric Cardiovascular Cardiovascular The onset of symptoms has been described in adults, but surveillance and medical management may be beneficial prior to adulthood Preventive measures, surveillance (eg, including echocardiography/electrocardiography), and medical management may be helpful to help decrease morbidity 16247757 TMPRSS15 9490 5651 Enterokinase deficiency AR Pediatric Gastrointestinal Gastrointestinal The condition tends to self-resolve, but early in life, pancreatic enzyme replacement or hydrolyzed formula can be beneficial 4180366; 4322674; 1147667; 943355; 6347801; 11719902 TMPRSS3 11877 64699 Deafness, autosomal recessive 10; Deafness, autosomal recessive 8 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 11137999; 11907649; 16021470; 23226338 TMPRSS6 16517 164656 Iron-refractory iron deficiency anemia AR Pediatric Hematologic Hematologic Variants may also affect hemoglobin levels The condition can involve anemia, which can be severe, and while oral iron therapy (as well as treatment with erythropoetin) alone may not be effective in all individuals (though some individuals have been reported who have been responsive to low-dose oral iron therapy), combination therapy with oral iron and ascorbic acid has been reported as beneficial, and parenteral iron therapy has been reported as partially effective in some individuals 7229750; 3354554; 8602626; 10524456; 11517621; 18408718; 18596229; 19786206; 21618415; 21643693; 21783390; 22169218; 23180434; 23319530 TMTC3 26899 160418 Lissencephaly 8 AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27773428 TMX2 30739 51075 Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31586943; 31735293 TNC 5318 3371 Deafness, autosomal dominant 56 AD N/A N/A Audiologic/Otolaryngologic General Deafness has been described as postlingual Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23936043 TNFAIP3 11896 7128 Autoinflammatory syndrome, familial, Behcet-like AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described with a multisystem autoinflammatory syndrome, and medical treatment (with TNF inhibitors or colchicine) has been described as beneficial 26642243 TNFRSF10B 11905 8795 Squamous cell carcinoma, head and neck AD Pediatric Oncologic Oncologic Surveillance and early diagnosis could potentially be beneficial to allow prompt management of detected neoplasms 9721851 TNFRSF11A 11908 8792 Familial expansile osteolysis; Paget disease of bone 2, early-onset; Osteopetrosis, autosomal recessive 7 AD/AR Pediatric (Polyostotic osteolytic dysplasia, hereditary expansile/Osteopetrosis, autosomal recessive 7); Adult (Paget disease of bone) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Dental; Endocrine; Musculoskeletal; Oncologic Allergy/Immunology/Infectious; Endocrine; Musculoskeletal; Oncologic In Osteopetrosis, autosomal recessive 7, individuals can present with hypocalcemic seizures, which are responsive to treatment; Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; In Polyostotic osteolytic dysplasia, hereditary expansile, HSCT has been reported as effective, including when performed in late infancy; For Paget disease of bone, medical management (eg, inhibitors of osteoclastic bone resorption) can be beneficial - bisphosphonates are current first line of treatment, and awareness of the risk of related oncologic processes (eg, osteosarcoma) may be beneficial to allow early diagnosis and treatment 3346299; 2530018; 9626117; 10615125; 11123042; 18606301; 18328984; 18672105; 19940926; 22271396 TNFRSF11B 11909 4982 Paget disease of bone 5, juvenile AR Pediatric Dental; Endocrine; Musculoskeletal Endocrine; Musculoskeletal Individuals may present with manifestations including osteopenia, fractures, and progressive skeletal deformity, and medical treatment (eg, with disodium etidronate, bisphosphonates, osteoprotegerin) has been reported as beneficial 13368018; 14123485; 5675396; 1593590; 8053403; 8770706; 12189164; 12124406; 14672344; 16135836; 17352649 ; 25108083 TNFRSF13B 18153 23495 Immunoglobulin A deficiency 2; Common variable immunodeficiency 2 AD/AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious In CVID2, prophylaxis and early and aggressive treatment of infections may be beneficial; In most cases, IGA deficiency 2 is not associated with any illness, though some may have increased infections and autoimmune disorders (other sequelae have been reported, but the molecular causes in these patients are unclear) 11720003; 16007086; 16049503; 16007087; 18981294; 19629655; 20156508; 22076597; 22627058 TNFRSF13C 17755 115650 Immunodeficiency, common variable 4 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Although the condition has only been described in adults, interventions may be indicated in the pediatric period Individuals may be susceptible to a number of infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 19666484 TNFRSF1A 11916 7132 Periodic fever, familial, autosomal dominant (TNF receptor-associated periodic syndrome) AD Pediatric Allergy/Immunology/Infectious; Dermatologic; Neurologic Allergy/Immunology/Infectious Individuals may manifest with sequelae such as periodic fever, pain, and rash, and medical treatment with TNF inhibitors (eg, etanercept) has been reported as effective in many individuals 1402641; 9585614; 9529351; 10199409; 10412980; 11115159; 11175303; 12584543; 17360963; 19381634; 21153346; 21225694; 21378401; 21869706; 22675839; 22281876 TNFRSF4 11918 7293 Immunodeficiency 16 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be susceptible to severe infections, as well as related oncologic sequelae (eg, Kaposi sarcoma), and early and aggressive treatment of infections and related sequelae may be beneficial 20156905; 23897980 TNFSF11 11926 8600 Osteopetrosis, autosomal recessive 2 AR Pediatric Audiologic/Otolaryngologic; Dental; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Hematologic; Musculoskeletal Individuals may present early in life with audiologic, neurologic, and ophthalmologic manifestations including hydrocephalus and visual impairment, as well as other findings including hepatosplenomegaly and fractures with poor bone remodeling, and awareness of complications may allow surveillance and prompt treatment; HSCT has been reported as beneficial 17632511 TNIK 30765 23043 Mental retardation, autosomal recessive 54 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27106596 TNNC1 11943 7134 Cardiomyopathy, familial hypertrophic 13; Cardiomyopathy, dilated, 1Z AD Pediatric Cardiovascular Cardiovascular Preventive measures, surveillance (eg, including echocardiography and electrocardiography), and medical management may be helpful to help decrease morbidity; Cardiac transplantation has been reported 11385718; 15542288; 18572189 TNNI2 11946 7136 Arthrogryposis, distal, type 2B1 AD N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12592607; 16802141 TNNI3 11947 7137 Cardiomyopathy, familial hypertrophic 7; Cardiomyopathy, dilated 1FF; Cardiomyopathy, dilated, 2A; Cardiomyopathy, familial restrictive 1 AD/AR Pediatric Cardiovascular Cardiovascular Preventive measures, surveillance (eg, including echocardiography and electrocardiography), and medical management may be helpful to decrease morbidity; Cardiac transplantation has been reported 3594932; 9241277; 9753711; 12531876; 15070570; 16267253; 19590045; 20569525; 21846512; 22301726; 22455086; 22876777; 23349452; 23396983; 23906401 TNNI3K 19661 51086 Cardiac conduction disease with or without dilated cardiomyopathy AD Pediatric Cardiovascular Cardiovascular Individuals have been described with arrhythmia and cardiomyopathy, and awareness may allow early medical/surgical management (eg, medical management and catheter-based ablation of cardiac foci has been described as beneficial) 24925317; 25791106; 30010057 TNNT1 11948 7138 Nemaline myopathy 5 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10952871; 29931346 TNNT2 11949 7139 Cardiomyopathy, familial restrictive, 3; Cardiomyopathy, dilated, 1D; Left ventricular noncompaction 6; Cardiomyopathy, familial hypertrophic, 2 AD Pediatric Cardiovascular Cardiovascular Preventive measures, surveillance (eg, including echocardiography and electrocardiography), and medical management may be helpful to help decrease morbidity 7981753; 8205619; 7898523; 9714088; 11106718; 11684629; 15542288; 16651346; 18506004; 18651846; 21483645; 21846512; 22144547; 22292720 TNNT3 11950 7140 Arthyrgryposis, distal, type 2B2 AD N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12865991 TNPO3 17103 23534 Muscular dystrophy, limb-girdle, autosomal dominant 2 AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11222786; 23543484; 23667635 TNRC6A 11969 27327 Epilepsy, familial adult myoclonic, 6 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29507423 TNRC6B 29190 23112 Global developmental delay with speech and behavioral abnormalities AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29463886; 32152250 TNXB 11976 7148 Vesicoureteral reflux 8; Ehlers-Danlos syndrome, classic-like AD/AR Pediatric Cardiovascular; Dermatologic; Gastrointestinal; Musculoskeletal; Renal Cardiovascular; Gastrointestinal; Renal Variants may also be involved in vesicoureteral reflux In Vesicoureteral reflux, monitoring and intervention related to renal sequelae may be beneficial in terms of helping to preserve renal function; In Ehlers-Danlos syndrome, reported features include aortic dilatation (which may not have a high risk of progression), severe diverticular intestinal disease with ruptured diverticula, pancolonic diverticulitis, and rectal prolapse, mitral valve prolapse requiring valve replacement, and obstructive airway disease, though it is not clear if these are all related to TNXB or to other genetic anomalies; Surveillance related to cardiovascular anomalies may be beneficial 9288108; 11642233; 12180144; 12865992; 15793839; 15733269; 19921645; 19557868; 20301456; 21959861; 23284009; 23620400; 23768946 TOE1 15954 114034 Pontocerebellar hypoplasia type 7 AR N/A N/A Craniofacial; Endocrine; Genitourinary; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21594990; 28092684 TOGARAM1 19959 23116 Joubert syndrome 37 AR N/A N/A Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Renal General The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32453716; 32747439 TONSL 7801 4796 Spondyloepimetaphyseal dysplasia, sponastrime type AR N/A N/A Allergy/Immunology/Infectious; Craniofacial; Dental; Endocrine; Hematologic; Musculoskeletal; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30773278; 30773278 TOP3A 11992 7156 Microcephaly, growth restriction, and increased sister chromatid exchange 2; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5 AR Pediatric (Microcephaly, growth restriction, and increased sister chromatid exchange 2); Adult (Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic Allergy/Immunology/Infectious; Cardiovascular In Microcephaly, growth restriction, and increased sister chromatid exchange 2, the condition can include frequent infections, and awareness may allow early and aggressive treatment of infections; Individuals have been described with cardiomyopathy, and awareness may allow surveillance and prompt management; In Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5, the condition may involve cardiac dysfunction, and awareness may allow early detection and management 29290614; 30057030 TOPORS 21653 10210 Retitinis pigmentosa 31 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16189705; 17924349; 18509552; 19183411 TOR1A 3098 1861 Dystonia 1, torsion; Arthrogryposis multiplex congenita 5 AD/AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9288096; 10541594; 10435508; 11523564; 12391355; 11973627; 12481989; 12402271; 12975293; 15326234; 16275837; 17503336; 18519876; 19955557; 20925076; 21515903; 22132914; 28516161; 29053766; 30244176 TOR1AIP1 29456 26092 Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures AR Pediatric Cardiovascular; Musculoskeletal; Neurologic; Pulmonary Cardiovascular; Pulmonary Individuals have been described with cardiomyopathy and pulmonary restrictive disease, and awareness may allow medical management 24856141 TOR1AIP2 24055 163590 Muscular dystrophy, limb-girdle, type 2Y AR N/A N/A Cardiovascular; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24856141 TP53 11998 7157 Li-Fraumeni syndrome; Choroid plexus papilloma; Ependymoma, intracranial; Osteogenic sarcoma; Breast cancer, familial; Hepatoblastoma; Non-Hodgkin lymphoma; Adrenocortical carcinoma; Colorectal cancer; Bone marrow failure syndrome 5 AD Pediatric Allergy/Immunology/Infectious; Hematologic; Neurologic; Oncologic Oncologic Variants may also be involved in susceptibility to a number of types of neoplasms (eg, Basal cell carcinoma, susceptibility to, Glioma, susceptibility to) For individuals with cancer predisposition, though the optimal course is unclear, surveillance (including breast cancer and colorectal cancer screening starting no later than age 25) and awareness of the increased risk of malignancy could potentially be beneficial in order to allow early diagnosis and treatment; Mastectomy is preferred to lumpectomy in individuals with breast cancer, and may be a prophylactic option; Radiation therapy should be avoided due to the risk of radiation-induced malignancies; For Bone Marrow failure syndrome, individuals have been described as requiring interventions such as blood transfusions and IgG replacement, and awareness may allow prompt management 6016796; 3409256; 1978757; 1679237; 1591732; 1349175; 1565144; 1565143; 8118819; 8718514; 7887414; 9242456; 10612830; 11332399; 11498785; 11600572; 11219776; 11481490; 12085209; 12610779; 12524418; 12619118; 14583457; 12619118; 15381368; 15695383; 15977174; 15741269; 18762572; 19171829; 19556618; 19652052; 20301488; 21056402; 21601526; 21837677; 21946351; 21990040; 22170717; 22551548; 22672556; 22878818; 22939227; 23015295; 23175693; 23355100; 23409989; 23667851; 23894400; 30146126 TP53RK 16197 112858 Galloway-Mowat syndrome 4 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28805828 TP63 15979 8626 Split-hand/foot malformation 4; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3; Limb-mammary syndrome; Rapp-Hodgkin syndrome; ADULT syndrome; Ankyloblepharon-ectodermal defects-cleft lip/palate; Orofacial cleft 8 AD N/A N/A Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5713637; 946410; 3366140; 9443880; 10535733; 9973291; 10886756; 10839977; 11528512; 11159940; 11462173; 11929852; 12838557; 12939657; 14684701; 12766194; 15200513; 16688749; 16740912; 17041931; 16724007; 17609671; 17431922; 18627043; 19239083; 18603493; 19697430; 19353643; 19676059; 19530185; 21204238; 21990121; 22065540; 22065614; 22069181; 22430731; 22574117; 22607287; 22740388; 29500247 TPCN2 20820 219931 Skin/hair/eye pigmentation, variation in, 10 AD N/A N/A Dermatologic General Variants may be involved in sun sensitivity The condition may not be clinically relevant 18488028 TPI1 12009 7167 Triosephosphate isomerase deficiency AR Pediatric Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Neurologic Allergy/Immunology/Infectious; Hematologic Surveillance and early treatment for complications affecting other organ systems, such as hematologic complications and cardiomyopathy can be beneficial (RBC transfusions have been described as beneficial); Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 2569601; 2876430; 3619568; 14242501; 1959537; 4065896; 6946452; 8244340; 8503454; 8639817; 9294216; 9338582; 10209987; 10782327; 10910933; 10916682; 11196750; 14984912; 17424909; 17879449; 19786097; 20374271; 21215915; 24056040 TPK1 17358 27010 Thiamine metabolism dysfunction syndrome 5 AR Pediatric Biochemical; Neurologic Biochemical In some individuals, thiamine supplementation appears to have beneficial effect (related compounds may be beneficial as well) 22152682 TPM1 12010 7168 Cardiomyopathy, dilated, 1Y; Cardiomyopathy, familial hypertrophic, 3 AD Pediatric Cardiovascular Cardiovascular Surveillance (eg, with echocardiography/electrocardiography), preventive measures and medical management, including ICD treatment, may be helpful to help decrease morbidity 8205619; 7898523; 11136687; 11273725; 21823217 TPM2 12011 7169 Nemaline myopathy 4; CAP myopathy 2; Arthrogryposis, distal, type 1A; Arthrogryposis, distal, type 2B AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11738357; 12592607; 17434307; 17846275; 19047562; 19345583; 22084935; 22798622; 22832343 TPM3 12012 7170 Nemaline myopathy 1, autosomal dominant; CAP myopathy; Myopathy, congenital, with fiber-type disproportion AD N/A N/A Craniofacial; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18300303 TPMT 12014 7172 Thiopurine S-methyltransferase deficiency AR Pediatric Biochemical Pharmacogenomic Dose adjustment/selection of specific medications (eg, azathioprine, cisplatin, mercaptopurine, s-adenoslymethionine, thioguanine) may be indicated in order to avoid severe toxicity 2758725; 1960624; 7862671; 8644731; 9177237; 11304783; 15228163; 16220112; 19898482 TPO 12015 7173 Thyroid dyshormonogenesis 2A AR Pediatric Endocrine; Oncologic Endocrine; Oncologic Medical treatment of hypothyroidism (eg, with T4) can be effective; Thyroid neoplasms have also been reported, and surveillance may be beneficial 1401057; 8027236; 9814507; 10084596 TPP1 2073 1200 Ceroid lipofuscinosis, neuronal, 2; Spinocerebellar ataxia, autosomal recessive 7 AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5634370; 5795346; 4116925; 3146310; 7668319; 9295267; 9788728; 10330339; 12376936; 15965709; 17959406; 18684116; 20820830; 21990111; 22612257; 23266810; 23418007; 26224725 TPP2 12016 7174 Immunodeficiency 78 with autoimmunity and developmental delay AR Pediatric Allergy/Immunology/Infectious; Hematologic; Neurologic Allergy/Immunology/Infectious Among other findings, the condition can involve early-onset immunodeficiency, with severe and recurrent infections, and awareness may allow preventative measures and early and aggressive treatment of infections; BMT has been described 25525876; 25414442; 33586135 TPRKB 24259 51002 Galloway-Mowat syndrome 5 AR N/A N/A Craniofacial; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28805828 TPRN 26894 286262 Deafness, autosomal recessive 79 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 19603065; 20170898; 23340767 TPSAB1 12019 7177 Irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia AD N/A N/A Allergy/Immunology/Infectious; Gastrointestinal; Musculoskeletal; Neurologic General Reported pathogenic variants have involved gene duplications or triplications Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27749843 TRAC 12029 28755 T-cell receptor-alpha/beta deficiency AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Prophylactic measures, surveillance, and early and aggressive treatment of infections may be beneficial; BMT has been described 21206088 TRAF3 12033 7187 Encephalopathy, acute, infection-induceed (herpes-specific), susceptibility to, 5 AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be susceptible to severe herpes simplex virus infections (eg, herpes encephalitis has been described), and awareness may allow early diagnosis and treatment (eg, with acyclovir, which has been reported as effective in the reported individual), potentially decreasing morbidity and mortality 20832341 TRAF3IP1 17861 26146 Senior-Loken syndrome 9 AR N/A N/A Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26487268 TRAF3IP2 1343 10758 Candidiasis, familial 8 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been reported as having recurrent candidal (and other) infections, and surveillance, prophylaxis, and early treatment may be beneficial 24120361 TRAF7 20456 84231 Cardiac, facial, and digital anomalies with developmental delay AD Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic Cardiovascular Among other findings, individuals have been described with heart anomalies (eg, including structural anomalies and arrthymia), and awareness may allow prompt diagnosis and management 25961944; 29961569 TRAIP 30764 10293 Seckel syndrome 9 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic; Pulmonary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26595769 TRAK1 29947 22906 Developmental and epileptic encephalopathy 68 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28364549; 28940097; 29846532 TRAP1 16264 10131 Congenital abnormalities of the kidney and urinary tract; VACTERL association AR Pediatric Cardiovascular; Gastrointestinal; Genitourinary; Musculoskeletal; Renal Renal The conditions may involve multiple congenital anomalies Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function 24152966 TRAPPC11 25751 60684 Muscular dystrophy, limb-girdle, autosomal recessive, 18 AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23830518; 27707803; 28827486 TRAPPC12 24284 51112 Encephalopathy, progressive, early-onset, with brain atrophy and spasticity (PEBAS) AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28777934 TRAPPC14 25604 55262 Microcephaly 25, primary, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30715179 TRAPPC2 23068 6399 Spondyloepiphyseal dysplasia tarda, X-linked XL N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10431248; 14755465; 15316971; 19002213; 19417549; 19766614; 20301324; 22563562; 23656395 TRAPPC2L 30887 51693 Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30120216 TRAPPC4 19943 51399 Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31794024 TRAPPC6B 23066 122553 Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28397838; 28626029 TRAPPC9 30832 83696 Mental retardation, autosomal recessive 13 AR N/A N/A Craniofacial; Endocrine; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17120046; 20004765; 20004763; 20004764; 21629298; 22549410; 22989526 TRDN 12261 10345 Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness AR Pediatric Cardiovascular; Neurologic Cardiovascular Individuals may present with severe cardiac manifestations, including arrhythmias, syncope, and sudden death, and surveillance, preventive measures (eg, including avoidance of dangerous or excacerbating factors), and treatment (eg, including interventions such as medical treatment with beta-blockers or ICD placement) may allow early and beneficial management, which may decrease morbidity and mortality 22422768 TREH 12266 11181 Trehalase deficiency AR N/A N/A Biochemical General The clinical significance is unclear 28406212 TREM2 17761 54209 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (Nasu-Hakola disease); Early-onset dementia without bone cysts AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12080485; 15883308; 1854636; 21834902; 23318515 TREX1 12269 11277 Aicardi-Goutieres syndrome 1 AD/AR Pediatric Allelic with Chilblain lupus 1 (AD); Vasculopathy, retinal, with cerebral leukodystrophy (AD) Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic; Pulmonary Cardiovascular; Pulmonary The condition may include pulmonary hypertension, and awareness may allow surveillance, prompt diagnosis of disease, and management of this sequelae 6712192; 3731164; 3174024; 1821204; 8592332; 9371916; 10449133; 15807828; 16845398; 16960810; 17440703; 17660818; 17846997; 17660820; 20301648; 20799324; 21808053; 22356656; 22829693; 30219631 TRHR 12299 7201 Hypothyroidism, congenital, nongoitrous, 7 AR Pediatric Endocrine Endocrine Individuals may manifest with sequalae of hypothyroidism, and medical treatment (with thyroid hormone replacement) can be effective 9141550; 19213692; 26735259; 28419241 TRIM2 15974 23321 Charcot-Marie-Tooth disease, axonal, type 2R AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23562820; 25893792 TRIM32 16380 22954 Muscular dystrophy, limb-girdle, , autosomal recessive, 8; Bardet-Biedl syndrome 11 AR N/A N/A Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition frequently involves multiple congenital anomalies and multisystemic manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4269389; 10399877; 11822024; 15886712; 15580560; 16243356; 15786463; 16606853; 17994549; 19492423; 20301537; 20177705; 21775502; 22981120 TRIM36 16280 55521 Anencephaly AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28087737 TRIM37 7523 4591 Mulibrey nanism AR Pediatric Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic Cardiovascular; Oncologic The condition may involve multiple malformations Surveillance and early detection of and treatment for malignancy (Wilms tumors, as well a number of other cancer types have been reported) may decrease morbidity and mortality; Awareness of cardiovascular anomalies (including structural anomalies, as well as pericardial constriction and congestive heart failure) may be beneficial in order to allow early diagnosis and treatment 4124529; 135512; 8335020; 10888877; 12754710; 14757854; 15108285; 15590968; 16306379; 17100991; 16310976; 17551331; 19329943; 19334051; 21865362; 23385855 TRIM44 19016 54765 Aniridia 3 AD Pediatric Ophthalmologic Ophthalmologic; Pharmacogenomic Individuals with may be at risk of developing glaucoma; Agents that may contribute to glaucoma should be avoided 26394807 TRIM71 32669 131405 Hydrocephalus, congenital communicating, 1 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29983323 TRIO 12303 7204 Intellectual developmental disorder, autosomal dominant 44, with microcephaly; Intellectual developmental disorder, autosomal dominant 63, with macrocephaly AD N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18388777; 26721934; 27418539; 32109419 TRIOBP 17009 11078 Deafness, autosomal recessive 28 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 16385457; 16385458; 23226338 TRIP11 12305 9321 Achondrogenesis, type IA; Odontochondrodysplasia AR N/A N/A Dental; Musculoskeletal; Pulmonary; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4885523; 7460382; 3275766; 18241073; 20089971; 30728324 TRIP12 12306 9320 Clark-Baraitser syndrome (Mental retardation, autosomal dominant 49) AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25363768; 27479843; 27848077; 28251352 TRIP13 12307 9319 Mosaic variegated aneuploidy syndrome 3 AR Pediatric Allelic with Oocyte maturation defect 9 (AR) Craniofacial; Musculoskeletal; Neurologic; Obstetric; Oncologic; Ophthalmologic Oncologic Increased susceptibility to other types of cancer has been suggested Individuals have been descriebd as susceptible to early-onset Wilms tumor, and awareness may allow early diagnosis and management 28553959; 32473092 TRIP4 12310 9325 Spinal muscular atrophy with congenital bone fractures 1; Muscular dystrophy, congenital, Davignon-Chauveau type AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26924529; 27008887 TRIT1 20286 54802 Combined oxidative phosphorylation deficiency 35 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28185376; 24901367 TRMT1 25980 55621 Intellectual developmental disorder, autosomal recessive 68 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21937992; 26308914; 30289604 TRMT10A 28403 93587 Microcephaly, short stature, and impaired glucose metabolism 1 AR Pediatric Craniofacial; Endocrine; Musculoskeletal; Neurologic Endocrine Awareness of the risk of diabetes mellitus may allow prompt recognition and treatment 24204302; 25053765 TRMT10C 26022 54931 Combined oxidative phosphorylation deficiency 30 AR N/A N/A Biochemical; Cardiovascular; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27132592 TRMT5 23141 57570 Combined oxidative phosphorylation deficiency 26 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26189817 TRMU 25481 55687 Liver failure, infantile, transient; Reversible infantile respiratory chain deficiency AR N/A N/A Biochemical; Gastrointestinal General In Liver failure, infantile, transient, with supportive care, patients surviving the initial acute episode can recover and demonstrate typical development; Genetic diagnosis may be beneficial in order to determine therapy Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12408186; 11230176; 19732863; 21931168; 21931168 TRNH 7487 4564 Deafness, nonsyndromic, sensorineural Maternal Pediatric Allelic with Myoclonic epilepsy with ragged red fibers (Maternal); Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (Maternal) Audiologic/Otolaryngologic; Biochemical; Gastrointestinal; Musculoskeletal; Neurologic Audiologic/Otolaryngologic As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Mitochondrial variants may involve a variety of sequelae, including hearing impairment, with highly variable age of onset, and for individuals with early-onset hearing impairment, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 14967777; 21931169 TRNI 7488 4565 Deafness, mitochondrial; Hypertension, hypercholesterolemia, and hypomagnesemia (Maternal) Maternal Pediatric Allelic with Cardiomyopathy, fatal (Maternal); Cardiomyopathy, familial hypertrophic (Maternal); Encephalopathy, familial progressive necrotizing (Maternal); Mitochondrial multisystemic disorder (Maternal) Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Renal Audiologic/Otolaryngologic; Renal Individuals have been described with a wide range of cardiovascular manifestations, including fatal infantile forms, as well as familial hypertrophic cardiomyopathy; Cardiac transplant has been described Treatment of electrolyte abnormalities, as well as blood pressure control, can be beneficial; For prelingual hearing loss, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Aminoglycosides should be avoided 11782991; 12767666; 15121771; 15498972; 1632786; 889580; 15121771; 15498972; 1978914; 22241583 TRNK 7489 4566 Parkinson disease, mitochondrial Maternal Adult Allelic with Myoclonic epilepsy with ragged red fibers (Maternal); Diabetes-deafness syndrome (Maternal); Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (Maternal) Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic; Renal Neurologic Mitochondrial variants may involve a variety of sequelae, including hearing impairment; The conditions can include features common to other mitochondrial disorders; As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Individuals with Parkinson disease have been reported as responding to therapies such as levodopa 2112427; 1463005; 8069654; 9571188; 17200493 TRNP 7494 4571 Myoclonic epilepsy with ragged red fibers Maternal N/A N/A Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic General Mitochondrial variants may involve a variety of sequelae, including hearing impairment; As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19273760 TRNQ 7495 4572 Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes Maternal N/A N/A Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic General Mitochondrial variants may involve a variety of sequelae, including hearing impairment Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11171912 TRNS2 7498 4575 Myoclonic epilepsy with ragged red fibers; Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; Retinitis pigmentosa-deafness syndrome Maternal N/A N/A Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic General Mitochondrial variants may involve a variety of sequelae, including hearing impairment; As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8364569; 9135384; 10090882; 16950817 TRNT 7499 4576 Mitochondrial myopathy, lethal Maternal N/A N/A Biochemical; Musculoskeletal; Neurologic General The pathogenicity of the reported variant is unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2549452; 1645537; 1379415 TRNT1 17341 51095 Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay AR Pediatric Allelic with Retinitis pigmentosa and erythrocytic microcytosis (AR) Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Hematologic; Neurologic; Ophthalmologic; Renal Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Hematologic Medical management (with immunoglobulin therapy) has been described as beneficial; Most patients have been described as requiring regular blood transfusions for treatment of anemia, as well as iron chelation; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; BMT has been described 25193871; 26494905 TRPA1 497 8989 Episodic pain syndrome, familial, 1 AD N/A N/A Neurologic General Individuals have been described as suffering from episodes of severe pain that could, to some extent, be predicted and ameliorated, but it is unclear if genetic diagnosis would be additionally advantageous (in addition to clinical diagnosis) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20547126 TRPC3 12335 7222 Spinocerebellar ataxia 41 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25477146 TRPC6 12338 7225 Focal segmental glomerulosclerosis 2 AD Pediatric Renal Renal The condition can involve renal failure, and early diagnosis may allow early management; Renal transplant has been described 10200986; 15924139; 15879175; 21415313; 21511817; 21734084 TRPM1 7146 4308 Night blindness, congenital stationary, type 1C AR N/A N/A Ophthalmologic General Dermatologic findings (eg, dry skin; a condition resembling epidermolysis bullosa simplex) have been described, but it is not clear if these are part of the core phenotype Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19896113; 19878917; 19896109; 20300565 TRPM4 17993 54795 Progressive familial heart block, type IB AD Pediatric Allelic with Erythrokeratodermia veriabilis et progressiva 6 (AD) Cardiovascular; Dermatologic Cardiovascular Preventive measures (eg, pacemakers and other medical measures) have been shown to be effective to control sequelae, which can include sudden death 897853; 619595; 4003252; 3750143; 3347879; 9023172; 19726882; 20562447; 21887725; 30528822 TRPM6 17995 140803 Hypomagnesemia 1, intestinal AR Pediatric Gastrointestinal Gastrointestinal Individuals typically present in infancy with manifestations of electrolyte imbalances (hypomagnesemia and consequent hypocalcemia) , which may result in death or severe neurologic impairment such that immediate magnesium administration can be effective in the acute period, though individuals require chronic high-dose oral magnesium supplementation 12032568; 12032570; 23942199 TRPS1 12340 7227 Trichorhinophalangeal syndrome, type I; Trichorhinophalangeal syndrome, type III AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5991804; 10615131; 11112658; 19419465; 19610100; 19758263; 20394624; 21740822; 22481165 ; 27133561 TRPV3 18084 162514 Olmsted syndrome 1; Palmoplantar keratoderma, nonepidermolytic focal 2 AD N/A N/A Dermatologic General Infections and skin cancer have been described at arising at the site of skin lesions Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22405088; 25285920 TRPV4 18083 59341 Avascular necrosis of femoral head, primary 2 AD N/A Allelic with Spinal muscular atrophy, distal, congenital nonprogressive (AD); Brachyolmia type 3 (AD); Metatropic dysplasia (AD); Spondyloepiphyseal dysplasia, Maroteaux type (AD); Scapuloperoneal spinal muscular atrophy (AD); Hereditary motor and sensory neuropathy, type Iic (AD); Spondylometaphyseal dysplasia, Kozlowski type (AD); Parastremmatic dwarfism (AD); Digital arthropathy-brachydactyly, familial (AD) Craniofacial; Musculoskeletal; Neurologic Musculoskeletal In Avascular necrosis of femoral head, primary, identifying carriers before the onset of clinical symptoms can allow interventions in order to delay disease progression 4992387; 4056805; 1520078; 8179305; 9781046; 10463355; 12884428; 14755468; 15668982; 17879966; 18348257; 18587396; 19232556; 20037588; 20425821; 21115951; 20577006; 20037587; 20037586; 20503319; 21336783; 21288981; 21964829; 21964574; 22065612; 22206013; 22419508; 22526352; 22617546; 22675077; 22791502; 22851605; 27330106 TRRAP 12347 8295 Developmental delay with or without dysmorphic facies and autism; Deafness, autosomal dominant 75; Schizophrenia AD N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23042115; 30424743; 31231791 TSC1 12362 7248 Tuberous sclerosis; Lymphangioleiomyomatosis AD Pediatric Allelic with Focal cortical dysplasia of Taylor (AD) Cardiovascular; Dental; Dermatologic; Neurologic; Oncologic; Ophthalmologic; Pulmonary; Renal Cardiovascular; Neurologic; Oncologic; Pulmonary; Renal Surveillance for and early treatment of tumors, as well as other manifestations affecting multiple organ systems (eg, renal anomalies, pulmonary manifestations, neurologic manifestations, and cardiac manifestations including arrhythmias) may reduce morbidity and mortality; Treatment with mTOR inhibitors may be beneficial related to neoplastic sequelae as well as related seizures; Lymphangiomyomatosis can occur as an isolated disorder or in association with TSC - the only effective therapy in late stage disease is transplant 14421523; 2823681; 3210031; 2706800; 8534286; 8592324; 8782048; 9132502; 9242607; 9863590; 9924605; 9579160; 11829138; 12112044; 14985384; 15257730; 15955990; 17003820; 17005952; 17304050; 18722871; 18032745; 19332694; 19419980; 21266383; 20301399; 21813552; 22189265; 22161988; 22490766; 23158522; 23743818; 23796861; 23845174; 23846400; 23851963; 23852707; 23909960 TSC2 12363 7249 Tuberous sclerosis 2; Lymphangioleiomyomatosis AD Pediatric Cardiovascular; Dental; Dermatologic; Neurologic; Oncologic; Ophthalmologic; Pulmonary; Renal Cardiovascular; Neurologic; Oncologic; Pulmonary; Renal Surveillance for and early treatment of tumors, as well as other manifestations affecting multiple organ systems (eg, renal anomalies, neurologic manifestations, pulmonary manifestations, and cardiac manifestations including arrhythmias) may reduce morbidity and mortality; Treatment with mTOR inhibitors may be beneficial related to neoplastic sequelae as well as related seizures; Lymphangiomyomatosis can occur as an isolated disorder or in association with TSC - the only effective therapy in late stage disease is transplant 14421523; 2823681; 3210031; 2706800; 1303246; 8162074; 8534286; 8824721; 8782048; 9302281; 9132502; 9463313; 9579160; 11829138; 14985384; 15955990; 17003820; 17005952; 17120248; 17304050; 18722871; 18032745; 19258298; 19332694; 19419980; 21266383; 21813552; 20301399; 22189265; 22490766; 23158522; 23733802; 23743818; 23757617; 23796861; 23845174; 23852707 TSEN15 16791 116461 Pontocerebellar hypoplasia type 2F AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25558065; 2739207 TSEN2 28422 80746 Pontocerebellar hypoplasia type 2B AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18711368; 23562994 TSEN34 15506 79042 Pontocerebellar hypoplasia, type 2C AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18711368 TSEN54 27561 283989 Pontocerebellar hypoplasia, type 2A; Pontocerebellar hypoplasia type 4; Pontocerebellar hypoplasia type 5 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8480512; 16470708; 18711368; 20956791; 21368912 TSFM 12367 10102 Combined oxidative phosphorylation deficiency 3 AR N/A N/A Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17033963; 21119709; 22499341 TSGA10 14927 80705 Spermatogenic failure 26 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28905369 TSHB 12372 7252 Hypothyroidism, congenital, nongoitrous, 4 AR Pediatric Endocrine Endocrine The untreated condition can result in severe neurological damage, and recognition can allow early medical treatment with thyroid hormone replacement can prevent such sequelae 2792087; 1971148; 8636437; 9589689; 11297590; 11549695; 12364478; 11788671; 15292359; 16804796 TSHR 12373 7253 Hyperthyroidism, familial, gestational; Hyperthyroidism, nonautoimmune; Hypothyroidism, congenital, nongoitrous, 1 AD/AR Pediatric Endocrine Endocrine Variants may also be associated with a number of thyroid-related presentations In Hyperthyroidism, familial, gestational, recognition and treatment of hyperthyroidism during pregnancy (eg, with propylthiouracil) can lead to positive gestational outcomes; In Hyperthyroidism (including in early-onset types), recognition can allow prompt treatment with medical or surgical ablation, as recurrent hyperthyroidism after subtotal thyroidectomy (necessitating repeat treatment), has been described; In conditions resulting in hypothyroidism, medical treatment of hypothyroidism (with T4) can be effective 7920658; 7800007; 7528344; 8954020; 9185526; 9329388; 9100579; 9385128; 9854118; 10487707; 12050212; 20146656; 20718767; 21186955; 21283701; 21677043; 21714469; 22405933; 22763653; 22876533; 23154162; 23329763; 23412867; 23563316; 23698639 TSHZ1 10669 10194 Aural atresia, congenital AD Pediatric Audiologic/Otolaryngologic; Craniofacial Audiologic/Otolaryngologic The condition may be recognizable from physical examination Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 22152683; 24487590 TSPAN12 21641 23554 Exudative vitreoretinopathy 5; Retinal dysplasia and severe familial exudative vitreoretinopathy AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20159111; 20159112; 20301326; 21334594; 21552475; 22427576 TSPAN7 11854 7102 Mental retardation, X-linked 58 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10449641; 10655063; 14735593 TSPEAR 1268 54084 Deafness, autosomal recessive 98 AR Pediatric Allelic with Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (AR) Audiologic/Otolaryngologic; Craniofacial; Dermatologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 22678063; 27736875 TSPYL1 12382 7259 Sudden infant death with dysgenesis of the testes syndrome; 46, XY disorder of sex development AR N/A N/A Genitourinary; Neurologic General In Sudden infant death with dysgenesis of the testes syndrome, death has been described during inpatient cardiorespiratory monitoring; In 46, XY disorder of sexual development, individuals may have the potential for gonadal tumors; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15273283; 19463995 TSR2 25455 90121 Diamond-Blackfan anemia 14 with mandibulofacial dysostosis XL Pediatric Audiologic/Otolaryngologic; Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Oncologic Audiologic/Otolaryngologic; Hematologic; Oncologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Specific treatment of anemia (eg, steroids, regular transfusions) can be effective; surveillance for and early treatment of malignancy may be beneficial; Individuals with DBA may manifest a variety of congenital malformations, and awareness may allow prompt detection and management 11424144; 24942156 TTBK2 19141 146057 Spinocerebellar ataxia 11 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18037885 TTC12 23700 54970 Primary ciliary dyskinesia 45 AR Pediatric Allergy/Immunology/Infectious; Genitourinary; Pulmonary Allergy/Immunology/Infectious; Pulmonary Pulmonary surveillance may be beneficial to assess respiratory function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial 31978331 TTC19 26006 54902 Mitochondrial complex III deficiency, nuclear type 2 AR N/A N/A Biochemical; Musculoskeletal; Neurologic General Individuals may suffer acute episodes of metabolic crisis; Treatment with "Mitochondrial cocktail" type therapy may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21278747; 23532514; 24368687; 24397319 TTC21B 25660 79809 Nephronophthisis 12; Short-rib thoracic dysplasia 4 with or without polydactyly AR N/A N/A Musculoskeletal; Neurologic; Ophthalmologic; Renal General The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20301500; 21258341 TTC29 29936 83894 Spermatogenic failure 42 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31735292; 31735294 TTC37 23639 9652 Trichohepatoenteric syndrome 1 AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal Allergy/Immunology/Infectious; Gastrointestinal The condition may be clinically recognizable, and prognosis may be poor in some individuals despite optimal therapy Individuals may also have immunodeficiency, and may benefit from prophylaxis and early and aggressive treatment of infections; Intractable diarrhea in infancy may require total parenteral nutrition; Patients may require hepatic transplant 70733018021782; 9021008; 9481629; 14521564; 15069414; 17236206; 17318842; 20176027; 21120949 TTC5 19274 91875 Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29302074; 32439809 TTC7A 19750 57217 Gastrointestinal defects and immunodeficiency syndrome AR N/A N/A Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal General HSCT has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23423984; 25174867 TTC8 20087 123016 Bardet-Biedl syndrome 8; Retinitis pigmentosa 51 AR N/A N/A Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Bardet-Biedl syndrome frequently involves multiple congenital anomalies and multisystemic manifestations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14520415; 16308660; 20301537; 20451172 TTI2 26262 80185 Mental retardation, autosomal recessive 39 AR N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21937992; 23956177 TTLL5 19963 23093 Cone-rod dystrophy 19 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24791901 TTN 12403 7273 Cardiomyopathy, familial hypertrophic 9; Cardiomyopathy, dilated, 1G AD Pediatric Allelic with Hereditary myopathy with early respiratory failure (AD); Tibial muscular dystrophy (AD); Salih myopathy (Myopathy, early-onset, with fatal cardiomyopathy) (AR); Muscular dystrophy, limb-girdle, autosomal recessive, 10 (AR) Cardiovascular; Musculoskeletal Cardiovascular Some allelic conditions have been reported as potentially including cardiovascular anomalies, but it is unclear if molecular diagnosis was uniformly verified Surveillance (including with echocardiography) may allow early detection and treatment, (including with interventions such as left ventricular assist device), and preventive measures may be additionally beneficial; Heart transplantation has been described 4855680; 126303; 196233; 6251174; 1619633; 1487757; 10053013; 10462489; 11788824; 12145747; 11846417; 12891679; 15802564; 17444505; 20627570; 22335739; 22577215; 22475360; 24105469 TTPA 12404 7274 Ataxia with vitamin E deficiency AR Pediatric Gastrointestinal; Neurologic Gastrointestinal Preventive treatment with vitamin E administration can ameliorate signs and symptoms of disease; Untreated, individuals typically present with neurological manifestations, including progressive ataxia, and knowledge can allow early treatment (which involves chronic supplementation with high-dose oral vitamin E, with the goal of maintaining plasma vitamin E concentrations in the high-normal range) 4000224; 3361234; 7887897; 7719340; 8602747; 8972536; 463307; 10552255; 11554913; 12039660; 15300460; 20301419 TTR 12405 7276 Amyloidosis, hereditary, transthyretin-related; Dystransthyretinemic hyperthyroxinemia AD Pediatric Allelic with Carpal tunnel syndrome, familial (AD) Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal Cardiovascular; Endocrine; Gastrointestinal; Neurologic In Familial transthyretin amyloidosis, surveillance for cardiovascular sequelae (which can include arrhythmias), and earlier treatment (eg, pacemaker) can be beneficial, and liver transplantation may be beneficial especially early in the disease course; Therapies involving transthyretin stabilization, RNA interference, or inhibtion of the hepatic production of transthyretin protein may be beneficial, especially in early stages of disease; In Dystransthyretinemic hyperthyroxinemia, diagnosis may be important in order to avoid unecessary treatment (eg, thyroid ablation) 13320157; 7417777; 6801514; 3229002; 1979335; 7839813; 8309582; 8784093; 8579098; 9017939; 10523220; 10869060; 11261421; 11385707; 11940682; 14640030; 14986482; 15249622; 15820680; 16357452; 15725588; 17554795; 19075702; 17200500; 18022643; 20301373; 22094129; 22843282; 23193944; 23483184; 23834402; 23901247; 23931808; 23984729; 23984729; 23993291; 24000164; 24023270; 24053266; 29972757 TUB 12406 7275 Retinal dystrophy and obesity AR N/A N/A Endocrine; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24375934 TUBA1A 20766 7846 Lissencephaly 3 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17218254; 17584854; 18728072; 18954413; 21403111; 22264709; 22633752; 22948023; 23317684; 23528852; 23361065 TUBA3D 24071 113457 Keraconus 9 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29051577 TUBA4A 12407 7277 Amyotrophic lateral sclerosis 22 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25374358 TUBA8 12410 51807 Polymicrogyria with optic nerve hypoplasia AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19896110 TUBB 20778 203068 Congenital symmetric circumferential skin creases 1; Cortical dysplasia, complex, with other brain malformations 6 AD N/A N/A Craniofacial; Dermatologic; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12239728; 23246003; 23324645; 26637975 TUBB1 16257 81027 Macrothrombocytopenia, autosomal dominant, TUBB1-related AD N/A N/A Hematologic General The clinical significance is unclear 15956286; 18849486 TUBB2A 12412 7280 Cortical dysplasia, complex, with other brain malformations 5 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24702957 TUBB2B 30829 347733 Cortical dysplasia, complex, with other brain malformations 7 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19465910; 22333901; 23361065; 23495813 TUBB3 20772 10381 Cortical dysplasia, complex, with other brain malformations 1; Fibrosis of extraocular muscles, congenital, 3A AD/AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7724178; 10393037; 12073023; 20829227; 20074521 TUBB4A 20774 10382 Dystonia 4, torsion, autosomal dominant; Leukodystrophy, hypomyelinating, 6 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3156966; 23582646; 23595291; 24013879; 24526230; 24742798; 24850488; 25085639 TUBB4B 20771 10383 Leber congenital amaurosis with early-onset deafness AD Pediatric Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 29198720 TUBB6 20776 84617 Facial palsy, congenital, with ptosis and velopharyngeal dysfunction (FPVEPD) AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29016863 TUBB8 20773 347688 Oocyte maturation defect 2 AD N/A N/A Obstetric General Attempts at IVF were not described as effective Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26789871 TUBG1 12417 7283 Cortical dysplasia, complex, with other brain malformations 4 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23603762 TUBGCP2 18599 10844 Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31630790 TUBGCP4 16691 27229 Microcephaly and chorioretinopathy, autosomal recessive 3 AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25817018 TUBGCP6 18127 85378 Microcephaly and chorioretinopathy, autosomal recessive 1 AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5936364; 22279524; 25344692 TUFM 12420 7284 Combined oxidative phosphorylation deficiency 4 AR N/A N/A Biochemical; Gastrointestinal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17160893 TULP1 12423 7287 Leber congenital amaurosis 15; Retinitis pigmentosa 14 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9462751; 9462750; 15024725; 15557452; 17620573; 18055821; 17962469; 20079931; 21792230; 21987678; 22605927; 22665969 TUSC3 30242 7991 Mental retardation, autosomal recessive 7 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18452889; 18455129; 21739581 TWIST1 12428 7291 Saethre-Chotzen syndrome; Robinow-Sorauf syndrome; Craniosynostosis 1; Sweeney-Cox syndrome AD N/A N/A Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal General Syndromic forms can involve multiple congenital anomalies, as well as hearing impairment in some individuals Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1240778; 7120316; 7120317; 8968762; 8988167; 8988166; 9585583; 10465122; 11977182; 12116251; 11772178; 12791045; 16251895; 17437280; 17343269; 19373776; 20301368; 27884935; 28369379 TWIST2 20670 117581 Ablepharon-macrostomia syndrome; Barber-Say syndrome; Focal facial dermal dysplasia 3, Setleis type AD/AR N/A N/A Craniofacial; Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1867254; 2036354; 3631024; 4412216; 8368246; 8746822; 8818454; 11038439; 11807864; 12210295; 15103726; 16650233; 14069095; 20799330; 20830793; 20691403; 21801849; 21931173; 26119818 TWNK 1160 56652 Mitochondrial DNA depletion syndrome 7 (hepatocerebral type); Perrault syndrome 5 AR Pediatric Allelic with Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3 (AD) Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal Biochemical Individuals may have biochemical manifestations, including fasting hypoglycemia responsive to glucose therapy 8133312; 7719341; 10522883; 11431692; 12210792; 16135556; 17921179; 17722119; 18775955; 18971204; 20479361; 20880070; 21519523; 21681116; 21689831; 22353293; 22928142; 23375728; 25355836 TXN2 17772 25828 Combined oxidative phosphorylation deficiency 29 AR Pediatric Biochemical; Neurologic Biochemical Medical management (with coenzyme Q10) has been described as beneficial 26626369 TXNL4A 30551 10907 Burn-McKeown syndrome AR Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial Audiologic/Otolaryngologic As the condition can include prelingual deafness, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 1342861; 14564154; 25434003 TXNRD2 18155 10587 Glucocorticoid deficiency 5 AR Pediatric Endocrine Endocrine Individuals have been described as having glucocorticoid deficiency, with poor cortisol response to ACTH stimulation, and required glucocorticoid replacement therapy 24601690 TYK2 12440 7297 Immunodeficiency 35 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 17088085; 17521577; 18270328; 26304966 TYMP 3148 1890 Mitochondrial DNA depletion syndrome 1 (MNGIE type) AR N/A N/A Biochemical; Gastrointestinal; Musculoskeletal; Neurologic General Liver transplantation has been described as resulting in short-term survival, stabilization of disease symptoms, decrease in thymidine levels, and clinical improvements. Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9924029; 10852545; 12177387; 14757860; 16178026; 18787099; 19056268; 19853446; 21412940; 21794876; 32173240 TYR 12442 7299 Albinism, oculocutaneous, type IA; Albinism, oculocutaneous, type IB AR N/A N/A Dermatologic; Ophthalmologic General Variants may also be related to pigmentary manifestations such as skin, eye, and hair color, and related risk of skin cancer Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 666627; 1970634; 8477259; 8190479; 9158138; 17999355; 17952075; 18488028; 19533789; 18488027; 19578364; 20806075; 20861488; 21458243; 21541274; 22294196 TYROBP 12449 7305 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (Nasu-Hakola disease) AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10888890; 12370476; 15049507; 15883308; 17125796; 22082900 TYRP1 12450 7306 Albinism, oculocutaneous, type III AR N/A N/A Dermatologic; Ophthalmologic General Variants may also be related to pigmentary manifestations such as skin, eye, and hair color, and related risk of skin cancer Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3935994; 8651291; 9345097; 16704458; 18680187; 19533799; 20861488; 21471978; 21996312; 22556244 UBA1 12469 7317 Spinal muscular atrophy, X-linked 2, infantile XL N/A N/A Musculoskeletal; Neurologic General Somatic variants can cause VEXAS syndrome, a muti-system autoinflammatory disorder Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18179898; 33108101 UBA5 23230 79876 Developmental and epileptic encephalopathy 44; Spinocerebellar ataxia, autosomal recessive 24 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26872069; 27545674; 27545681 UBAP1 12461 51271 Spastic paraplegia 80, autosomal dominant AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30929741; 31203368 UBE2A 12472 7319 Mental retardation, X-linked, syndromic, Nascimento-type XL N/A N/A Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16909393; 20339384; 20412111; 21108393 UBE2T 25009 29089 Fanconi anemia, complementation group T AR Pediatric Hematologic; Musculoskeletal; Neurologic; Oncologic Hematologic; Oncologic In Fanconi anemia, specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended 20301575; 26046368 UBE3A 12496 7337 Angelman syndrome AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8988171; 8988172; 9546330; 10196695; 11748306; 12210318; 15150776; 20034088; 20933619; 21072004; 21204213; 21362313; 21397058; 22065487 UBE3B 13478 89910 Kaufman oculocerebrofacial syndrome (Blepharophimosis-ptosis-intellectual disability syndrome) AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23200864 UBIAD1 30791 29914 Schnyder corneal dystrophy AD N/A N/A Ophthalmologic General Phototherapeutic keratectomy has been described as beneficial in this type of corneal dystrophy, though the advantage of early (genetic) diagnosis is unclear Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3486394; 8190477; 9450854; 10442892; 15034782; 17668063; 17962451; 18176953; 19429578; 19649163; 20489584; 20505825; 22065921 UBQLN2 12509 29978 Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21857683; 24771548 UBR1 16808 197131 Johanson-Blizzard syndrome AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Cardiovascular; Endocrine; Gastrointestinal; Hematologic; Neurologic; Ophthalmologic Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Gastrointestinal; Hematologic Medical treatment of exocrine pancreatic insufficiency can be beneficial; Awareness of cardiovascular manifestastions (which can include structural malformations as well as cardiomyopathy) can allow early diagnosis and treatment; As the condition can include congenital deafness, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Treatment of endocrine manifestations, such as hypothyroidism, growth hormone deficiency, and diabetes mellitus, can be beneficial; Severe anemia requiring transfusions has been described, and awareness may allow prompt diagnosis and treatment 5171616; 728568; 474625; 4050852; 2645405; 12535044; 12725595; 14647752; 15379429; 16311597; 16632090; 17378628; 18553553; 19058315; 19006206; 19717322; 20556423; 21931868; 20556422; 21429315; 21711208; 22072859; 23463671; 23778732; 24052374 UBR7 20344 55148 Li-Campeau syndrome AR Pediatric Cardiovascular; Craniofacial; Endocrine; Genitourinary; Neurologic; Musculoskeletal Endocrine Among other features, the condition can include hypothyroidism, and awareness may allow medical management 33340455 UBTF 12511 7343 Neurodegeneration, childhood-onset, with brain atrophy AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28777933 UCHL1 12513 7345 Parkinson disease 5, autosomal dominant; Spastic paraplegia 79, autosomal recessive AD Adult Allelic with Spastic paraplegia 79, autosomal recessive (AR) Neurologic; Ophthalmologic Neurologic For Parkinson disease 5, autosomal dominant, findings have not been replicated, and gene association has been described as uncertain Levodopa response has been reported 9774100; 16450370; 23359680 UFC1 26941 51506 Neurodevelopmental disorder with spasticity and poor growth AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27431290; 29868776 UFM1 20597 51569 Leukodystrophy, hypomyelinating, 14 AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27545674; 28931644; 29868776 UFSP2 25640 55325 Hip dysplasia, Beukes type; Spondyloepimetaphyseal dysplasia, Di Rocco type AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 2389793; 28892125 UGDH 12525 7358 Developmental and epileptic encephalopathy 84 (Jamuar syndrome) AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32001716 UGP2 12527 7360 Developmental and epileptic encephalopathy 83 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31820119 UGT1A1 12530 54658 Crigler-Najjar syndrome, type I; Crigler-Najjar syndrome, type II; Gilbert syndrome AD/AR Pediatric Allelic with Breast milk jaundice (AD/AR) Gastrointestinal Gastrointestinal; Pharmacogenomic In CNI, phototherapy (or other interventions, such as plasmapharesis), followed by liver transplantation may be beneficial; In CNII, not all individuals have severe forms of disease necessitating treatment, but patients with severe forms typically respond to phenobarbital treatment; Knowledge of the cause of jaundice even in less severe cases can help avoid prolonged etiologic work-ups; While Gilbert syndrome is not as severe as other disorders of hyperbilirubinemia, drug metabolism related to certain medications (eg, acetaminophen, atazanavir, irinotecan) imay be affected, and medication and dosing choice may be beneficial 12983120; 5685361; 805737; 3546653; 1734381; 1531971; 8276413; 7989595; 7565971; 8528206; 8690398; 9413009; 9580649; 9621515; 10412811; 11003624; 11061796; 11316168; 11370628; 11906189; 16712705; 18518849; 22676194; 22710376; 23099197; 23162302; 23241680; 23279026; 23403257; 23430851; 23926009; 23992562; 24065680 UMOD 12559 7369 Tubulointerstitial kidney disease, autosomal dominant, 1; Glomerulocystic kidney disease with hyperuricemia and isosthenuria AD Pediatric Allelic with Medullary cystic kidney disease 2 (AD) Renal Renal In some forms of MCKD2, it appears that isolated cysts can occur without hyperuricemia In Glomerulocystic kidney disease with hyperuricemia and isosthenuria and Tubulointerstitial kidney disease, autosomal dominant, medical treatment may be beneficial (eg, allopurinol related to gout and preservation of renal function) 7396593; 1975911; 1873940; 9266353; 9686952; 10780922; 12205338; 12471200; 14570709; 12634862; 12629136; 16883323 UMPS 12563 7372 Orotic aciduria AR Pediatric Allergy/Immunology/Infectious; Biochemical; Hematologic; Neurologic Biochemical Pyrimidine replacement therapy, along with urinary orotic acid monitoring, can be beneficial 13651334; 14110033; 5347440; 6828110; 6717503; 9042911; 19562503 UNC119 12565 9094 Immunodeficiency 13 AR Pediatric Allelic with Cone-rod dystrophy 2 (AD) Ophthalmologic General In Immunodeficiency 13, the described invidiual suffered from frequent and severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 11006213; 22184408 UNC13D 23147 201294 Hemophagocytic lymphohistiocytosis, familial 3 AR Pediatric Allergy/Immunology/Infectious; Hematologic; Oncologic Allergy/Immunology/Infectious; Hematologic; Oncologic Early recognition may allow prompt treatment, as individuals frequently have fatal outcomes unless treated by control of infectious triggers and chemoimmunotherapy, followed by HSCT 14622600; 16825436; 16278825; 17993578; 20301617; 21881043; 21303357; 21755595; 21931115; 22146525; 21674762 UNC45B 14304 146862 Myofibrillar myopathy 11 AD Pediatric Allelic with Cataract 43 (AD) Cardiovascular; Musculoskeletal; Ophthalmologic Cardiovascular Among other findings, the condition can involve arrhthymias and cardiomyopathy, and awareness may allow surveillance and early management of these sequelae 24549050; 31852522; 33217308 UNC80 26582 285175 Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26862157; 26708751; 26708753 UNC93B1 13481 81622 Herpes simplex encephalitis, susceptibility to, 1 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals may be susceptible to severe HSV infections, which can result in lethal sequlae or severe chronic impairment, and recognition may allow preventive measures as well as prompt treatment with anti-HSV medications (eg, acyclovir), which may improve outcome 16973841 UNG 12572 7374 Immunodeficiency with hyper-IgM, type 5 AD Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Due to low/absent serum IgG, IgA, and IgE, Individuals are susceptible to recurrent/severe bacterial infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 12958596; 15358621 UPB1 16297 51733 Beta-ureidopropionase deficiency AR N/A N/A Biochemical; Neurologic General As with many disorders involving seizure risk, optimal control is beneficial; Normal neurologic development has been described (in addition to severe neurologic manifestations) Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15385443; 17964839; 22525402 UPF3B 20439 65109 Mental retardation, X-linked, syndromic 14 XL N/A N/A Craniofacial; Musculoskeletal; Neurologic General Nonsyndromic forms have been described in addition to the initial reports of individuals with syndromic mental retardation Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9805132; 17704778; 19377476; 22957832 UPK3A 12580 7380 Renal/urogenital adysplasia AD N/A N/A Genitourinary; Renal General The condition has been described as involving progressive, inexorable renal failure, and renal transplant has been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15888565 UQCC2 21237 84300 Mitochondrial complex III deficiency, nuclear type 7 AR N/A N/A Biochemical; Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24385928 UQCC3 34399 790955 Mitochondrial complex III deficiency, nuclear type 9 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25008109 UQCRB 12582 7381 Mitochondrial complex III deficiency, nuclear type 3 AR N/A N/A Biochemical; Gastrointestinal General Individuals may suffer acute episodes of metabolic crisis; Treatment with "Mitochondrial cocktail" type therapy may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12709789 UQCRC1 12585 7384 Parkinsonism with polyneuropathy AD Adult Neurologic Neurologic Response to levodopa and anticholinergics has been described 33141179 UQCRC2 12586 7385 Mitochondrial complex III deficiency, nuclear type 5 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23281071 UQCRFS1 12587 7386 Mitochondrial complex III deficiency, nuclear type 10 AR Pediatric Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Neurologic Biochemical; Cardiovascular Individuals have been described as benefitting from medical management (with coenzyme Q10 supplementation); Individuals have been described with cardiomyopathy, and awareness may allow early detection and management 31883641 UQCRQ 29594 27089 Mitochondrial complex III deficiency, nuclear type 4 AR N/A N/A Biochemical; Neurologic General Individuals may suffer acute episodes of metabolic crisis; Treatment with "Mitochondrial cocktail" type therapy may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 18439546 UROC1 26444 131669 Urocanase deficiency AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 5124677; 6107814; 19304569 UROD 12591 7389 Porphyria, hepatoerythropoietic; Porphyria cutanea tarda AD/AR Pediatric Biochemical; Dermatologic; Gastrointestinal; Hematologic Dermatologic; Hematologic; Pharmacogenomic Treatment involves management of iron overload (eg, by phlebotomy); Exacerbating factors (eg, iron overload, excessive alcohol use, polyhalogenated aromatic chemicals, estrogens, etc.) should be avoided; Skin protection is warranted 5697519; 5455563; 4640947; 5080345; 4729688; 4739135; 993332; 871403; 730158; 661929; 758588; 463934; 253381; 7369748; 7428280; 6112327; 7062951; 7059676; 6375356; 3775362; 3808000; 3821794; 3348969; 2920211; 1442894; 8644733; 9792863; 12030801; 17295179; 20955974; 21668429; 22382040; 23545314 UROS 12592 7390 Porphyria, congenital erythropoietic AR Pediatric Dermatologic; Hematologic Dermatologic; Hematologic Transfusions can be beneficial; Individuals can prevent with bleeding diatheses, and prompt treatment may be beneficial; Limitation to sun exposure may be beneficial due ot photosensitivity; Manifestations such as thrombocytopenia and hemolytic anemia, may be effectively treated by splenectomy; Use of oral sorbents have been described; BMT has been described in severe cases 7205063; 3960070; 3100953; 2331520; 2207013; 8829650; 9834209; 12060112; 15703981; 22090724; 22350154; 22816431; 23557135; 23626549 USB1 25792 79650 Poikiloderma with neutropenia AR Pediatric Allergy/Immunology/Infectious; Dermatologic Allergy/Immunology/Infectious Individuals may also be at risk for leukemia and related processes Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial 18925663; 20004881; 20503306 USH1C 12597 10083 Usher syndrome, type IC; Deafness, autosomal recessive 18A AR Pediatric Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic Hearing loss has been described as late-onset in some individuals Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 5937908; 9653658; 10973248; 10973247; 12107438; 2136232; 23251578 USH1G 16356 124590 Usher syndrome, type 1G AR Pediatric Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12588794 USH2A 12601 7399 Usher syndrome, type 2A AR Pediatric Allelic with Retinitis pigmentosa 39 (AR) Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; It has been suggested that that stapes surgery should not be performed due to a high likelihood of complications (the use of cochlear implants has been reported as beneficial) 1580321; 9624053; 10775529; 10729113; 12427073; 15015129; 16301217; 16098008; 15671307; 17085681; 17296898; 18273898; 19881469; 20440071; 20301515 USP18 12616 11274 Pseudo-TORCH syndrome 2 AR N/A N/A Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12833411; 27325888 USP27X 13486 389856 Mental retardation, X-linked 105 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25644381 USP45 20080 85015 Leber congenital amaurosis 19 AR N/A N/A Ophthalmologic General Leber congenital amaurosis 19 30573563 USP7 12630 7874 Hao-Fountain syndrome AD N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26365382; 30679821 USP9X 12632 8239 Mental retardation, X-linked 99; Mental retardation, X-linked 99, syndromic, female restricted XL N/A N/A Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19377476; 24607389; 26833328 USP9Y 12633 8287 Spermatogenic failure, Y-linked, 2 YL N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9384609; 10402373; 10507722; 10581029; 10767340; 16893908; 18205040; 19246359 UTP4 1983 84916 North American Indian childhood cirrhosis AR Pediatric Gastrointestinal Gastrointestinal Individuals may initially present with neonatal cholestatic jaundice, and the condition may progress to end-stage, severe liver failure; Liver transplantation has been described as effective, and individuals have been described as dying before liver transplantation was available 6894906; 10820129; 11045837 UVSSA 29304 57654 UV-sensitive syndrome 3 AR N/A N/A Dermatologic General Increased risk of skin tumors has not been reported Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7513056; 3974603; 3774595; 22466610; 22466612 VAC14 25507 55697 Striatonigral degeneration, childhood-onset AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27292112 VAMP1 12642 6843 Myasthenic syndrome, congenital, 25, presynaptic AR Pediatric Allelic with Spastic ataxia 1, autosomal dominant (AD) Musculoskeletal; Neurologic Musculoskeletal; Neurologic The condition can involve neonatal hypotonia and generalized muscle weakness, and medicial management (with pyridostigmine) has been described as beneficial 11774073; 22958904; 28168212; 28253535; 28600779 VAMP2 12643 6844 Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30929742 VANGL1 15512 81839 Caudal regression syndrome; Neural tube defects AD N/A N/A Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17409324 VANGL2 15511 57216 Neural tube defects AD N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20558380; 20738329 VAPB 12649 9217 Amyotrophic lateral sclerosis 8; Spinal muscular atrophy, late-onset, Finkel type AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15372378; 18322265; 20940299; 20577002 VARS1 12651 7407 Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26539891; 29691655 VARS2 21642 57176 Combined oxidative phosphorylation deficiency 20 AR N/A N/A Biochemical; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24827421; 25058219; 31064326 VAX1 12660 11023 Microphthalmia, syndromic 11 AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22095910 VCAN 2464 1462 Wagner vitreoretinopathy AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9098284; 16043844; 16636652; 19901218; 20301747; 21738396; 22739342 VCL 12665 7414 Cardiomyopathy, familial hypertrophic 15; Cardiomyopathy, dilated, 1W AD Adult Cardiovascular Cardiovascular Surveillance (including with echocardiography, as asymptomatic individuals with variants have been found to have detectable disease prior to clinical presentation), preventive measures, and early medical management may be helpful to help decrease morbidity and mortality related to cardiomyopathy 11815424; 16712796; 16236538 VCP 12666 7415 Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Charcot-Marie-Tooth disease type, axonal type, 2Y; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7182974; 15034582; 16247064; 18260132; 18341608; 19704082; 19380227; 21145000; 21320982; 21984748; 22909335; 23152587; 25125609; 25878907 VDR 12679 7421 Vitamin D-dependent rickets, type 2A AD/AR Pediatric Dermatologic; Endocrine; Musculoskeletal Endocrine Treatment of manifestations such as rickets (eg, with vitamin D3, calcium, phosphate) can be beneficial in some individuals, though not all individuals have been reported as demonstrating clinical or laboratory-based response to treatments 205789; 233695; 221630; 6102232; 7318845; 3009551; 3024987; 3040300; 2849209; 2551693; 9005998; 17970811; 19815438; 19921089; 21073129; 21424181; 21590741; 21812032; 21860566; 22145479; 22145480; 23026218 VEGFC 12682 7424 Lymphatic malformation 4 AD N/A N/A Dermatologic General Individuals may be susceptible to recurrent skin infections Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23410910; 24744435 VHL 12687 7428 Von Hippel Lindau; Erythrocytosis, familial, 2 (Chuvash polycythemia); Pheochromocytoma AD/AR Pediatric Cardiovascular; Hematologic; Oncologic Cardiovascular; Hematologic; Oncologic Depending on the condition, individuals can have primarily oncologic (Von Hippel Lindau) or hematologic (Chuvash polycythemia) manifestations In VHL, surveillance for and early treatment of malignant complications (eg, hypertension and hypokalemia resulting from pheochromocytoma, as in isolated Pheochromocytoma) may be beneficial; Individuals with Erythrocytosis, familial, 2 have a high risk for peripheral thrombosis and cerebrovascular events, and preventive measures and early treatment may be beneficial, though the efficacy of interventions such as phlebotomy is questionable 13494077; 14142412; 4453572; 449657; 573913; 431135; 3790978; 2897130; 3200963; 2642584; 2066108; 1673491; 1347089; 1593692; 1436350; 8493574; 7987306; 7977949; 8059782; 8069305; 8592333; 8825918; 8929948; 9329368; 9398721; 9145719; 9058738; 9215674; 9663592; 10408776; 10554035; 10697963; 10830910; 11106358; 11097604; 10631138; 11688380; 11987242; 12415268; 12629069; 12844285; 14500227; 14726398; 15190140; 14695531; 14711727; 15599750; 15642664; 16210343; 17057815; 16518846; 17609489; 17311301; 19464396; 20151405; 20301636; 21606165; 21713522; 21972040; 21993671; 22265326; 22393103; 23781388; 23827964; 23897319; 23968328 VIM 12692 7431 Cataract 30, multiple types AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19126778 VIPAS39 20347 63894 Arthrogryposis, renal dysfunction, and cholestasis 2 AR N/A N/A Gastrointestinal; Musculoskeletal; Renal General The condition can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20190753; 23636179 VKORC1 23663 79001 Vitamin K-dependent clotting factors, combined deficiency of, 2; Drug metabolism, VKORC1-related AD/AR Pediatric Hematologic Hematologic; Pharmacogenomic Individuals may present with severe bleeding episodes (including, for example, fatal neonatal intracranial hemorrhage), and oral administration of vitamin K typically reverses bleeding tendency; Variants may have pharmacogenomic relevance (related to Drug metabolism, VKORC1-related) in regards to selection and dosing of medications (including warfarin) 11154138; 12384421; 14765194; 15930419; 15947090; 15888487; 16611310; 17653141; 18466099; 18535201; 18855533; 19207028; 19228618; 19300499; 20203262; 20833980; 19794411; 21148049; 22431865; 22528326; 23215886; 23276529; 23277416; 23279643; 23677510 VLDLR 12698 7436 Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 1 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16080122; 18043714; 18326629; 18364738; 20082205 VMA21 22082 203547 Myopathy, X-linked, with excessive autophagy XL N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23315026; 23850239; 25683699; 25809233; 25817839 VPS11 14583 55823 Leukodystrophy, hypomyelinating 12 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26307567 VPS13A 1908 23230 Choreoacanthocytosis AR N/A N/A Hematologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4255726; 5677189; 4647152; 666266; 7081216; 7073550; 4026606; 1998879; 7936287; 8599563; 9382101; 10371080; 11381253; 11381254; 12404112; 15918062; 15824261; 17998451; 18584183; 18661137; 20301561; 21598378; 22038564; 23199253 VPS13B 2183 157680 Cohen syndrome AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic Allergy/Immunology/Infectious The condition may be frequently recognizable due to characteristic features, including dysmorphisms Though the condition may be frequently recognizable, individuals can have recurrent infections, and antiinfectious prophlyaxis and treatment (including G-CSF for neutropenia), as well as early and aggressive treatment of infections may be beneficial 4717588; 671157; 7438489; 7246618; 7166592; 6705238; 3989828; 3656371; 3223494; 9266925; 10466416; 10964838; 12676892; 12730828; 15211651; 15025727; 15141358; 20683995; 20301655; 20921020; 24311531 VPS13C 23594 54832 Parkinson disease 23, autosomal recessive, early onset AR Adult Neurologic Neurologic Individuals have been described with levodopa response 26942284 VPS13D 23595 55187 Spinocerebellar ataxia, autosomal recessive 4 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29518281; 29604224 VPS16 14584 64601 Dystonia 30 AD/AR Pediatric Neurologic Neurologic Response to deep brain stimulation has been described 27174565; 32808683; 33482438 VPS33A 18179 65082 Mucopolysaccharidosis-plus syndrome AR N/A N/A Biochemical; Cardiovascular; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27547915; 28013294 VPS35 13487 55737 Parkinson disease 17 AD Adult Neurologic Neurologic Individuals have been described with levodopa response 18342564; 21763482; 21763483; 22517097; 23408866; 23623008 VPS37A 24928 137492 Spastic paraplegia 53, autosomal recessive AR N/A N/A Neurologic General The use of botulinum has been described as beneficial for treating spasticity in some individuals, though the advantage of genetic diagnosis is unclear; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22717650 VPS39 20593 23339 Schizophrenia AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23042115 VPS45 14579 11311 Neutropenia, severe congenital, 5, autosomal recessive AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious Individuals have been described with frequent and severe infections, and awareness may allow prophylactic measures (including treatment with G-CSF), as well as early and aggressive treatment of infections; HSCT has been described 23599270; 23738510 VPS4A 13488 27183 CIMDAG syndrome AD Pediatric Craniofacial; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic Hematologic Among other findings, individuals have been described as having transfusion-dependent anemia, and awareness may allow early diagnosis and medical management 33186543; 33186545; 33460484 VPS51 1172 738 Pontocerebellar hypoplasia, type 13 AR N/A N/A Craniofacial; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30624672; 31207318 VPS53 25608 55275 Pontocerebellar hypoplasia, type 2E AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24577744 VRK1 12718 7443 Pontocerebellar hypoplasia type 1A AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19646678; 21937992 VSX1 12723 30813 Craniofacial anomalies and anterior segment dysgenesis syndrome; Keratoconus 1; Corneal dystrophy, posterior polymorphous AD N/A N/A Craniofacial; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11978762; 15051220; 15623752; 16735990; 18216574; 18626569; 19763142; 19956409; 20664914; 21365019; 21976959; 26045363 VSX2 1975 338917 Microphthalmia, isolated 2; Microphthalmia, isolated, with coloboma 3 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3378363; 10932181; 15257456; 17661825; 18648522 VWA1 30910 64856 Neuropathy, hereditary motor, with myopathic features AR N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 33459760; 33559681 VWA3B 28385 200403 Spinocerebellar ataxia, autosomal recessive 22 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26157035 VWF 12726 7450 von Willebrand disease, type 1; von Willebrand disease, type 2A; von Willebrand disease, type 3 AD Pediatric Hematologic Hematologic; Pharmacogenomic There are a number of treatments depending on the subtype of disease; Treatments include control of severe bleeding episodes (eg, with IV infusion of plasma-derived clotting factor, or IV/SQ desmopressin), as well as fibrinolytic inhibitors and hormones for menorrhagia; Primary prevention can be instituted via prophylactic VWF/FVIII infusions; Among a number of important preventive measures, specific medications should be avoided, including ASA, clopidogrel, NSAIDS 315519; 6972630; 6412139; 3116703; 3033024; 3257148; 3258663; 2895123; 2297569; 8456431; 8456432; 8367445; 8052974; 8839833; 9253800; 10444292; 10669167; 11756169; 12649144; 15306670; 17080221; 16889557; 16985174; 17190853; 19085649; 20409624; 22428722; 22458923; 22482515; 22531022; 22530576; 22722677; 22726101; 22823000; 22906074; 22957493; 23034827; 23109357; 23109385 WAC 17327 51322 DeSanto-Shinawi syndrome AD N/A N/A Craniofacial; Gastrointestinal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25356899; 26264232 WARS1 12729 7453 Neuronopathy, distal hereditary motor, type IX AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28369220; 31069783; 31321409 WARS2 12730 10352 Neurodevelopmental disorder, mitochondrial with abnormal movements and lactic acidosis and with or without seizures (NEMMLAS) AR N/A N/A Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28236339; 28650581; 28905505 WAS 12731 7454 Wiskott-Aldrich syndrome; Thrombocytopenia 1; Neutropenia, severe congenital, X-linked XL Pediatric Allergy/Immunology/Infectious; Dermatologic; Hematologic Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic Individuals can have immune dysfunction, such as in SCNX, which is due to constitutively activating variants Prophylaxis and early and aggressive treatments for infections, and avoidance of circumstances that would result in severe bleeding, including certain medications, may be beneficial; HSCT, and genetically modified HSCT (gene therapy) have been described 13133561; 4177931; 4177932; 3995178; 3284030; 1960605; 8279047; 8069912; 7795648; 7537115; 1611094; 7579347; 8682510; 10575547; 8931701; 10447259; 11242115; 11447283; 15142877; 11238097; 11242115; 16804117; 17065640; 17065636; 17250667; 19006568; 18724301; 18479478; 20301357; 21067383; 22052860; 22338148; 22426750; 22456069; 22523910; 23023736; 23237501; 23264593; 23343520; 23498591; 23527602; 23845947; 23943155 WASF1 12732 8936 Neurodevelopmental disorder with absent language and variable seizures AD N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29961568 WASHC4 29174 23325 Mental retardation, autosomal recessive 43 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21498477 WASHC5 28984 9897 Spastic paraplegia 8; Ritscher-Schinzel syndrome 1 (3C syndrome) AD/AR N/A N/A Cardiovascular; Craniofacial; Neurologic; Ophthalmologic General Ritscher-Schinzel syndrome (3C syndrome) may involve multiple congenital anomalies, including cardiovascular malformations Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7604842; 10797436; 17160902; 20301727; 23455931; 24065355 WBP11 16461 51729 Vertebral, cardiac, tracheoesophageal, renal, and limb defects AD Pediatric Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Pulmonary; Neurologic; Renal Audiologic/Otolaryngologic; Cardiovascular Individuals have been described with hearing impairment, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with congenital cardiac anomalies, some of which required intervention, and awareness may allow surveillance and early management 33276377 WBP2 12738 23558 Deafness, autosomal recessive 107 AR Pediatric Audiologic/Otolaryngologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 26881968 WDFY3 20751 23001 Microcephaly, 18, primary, autosomal dominant AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27008544 WDPCP 28027 51057 Bardet-Biedl syndrome 15; Congenital heart defects, hamartomas of tongue, and polysyndactyly; Meckel-Gruber syndrome type 6, modifier of AR N/A N/A Cardiovascular; Craniofacial; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal General Variants may modify severity of BBS and related disorders due to variants in other BBS-associated genes Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20671153; 25427950 WDR11 13831 55717 Hypogonadotropic hypogonadism 14 with or without anosmia AD Pediatric Endocrine; Neurologic General Surveillance in adolescence related to sexual maturation is indicated, and in order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required Monitoring of bone mineral density is indicated in order to allow early detection and treatment of disease 20887964 WDR19 18340 57728 Short-rib thoracic dysplasia 5 with or without polydactyly; Cranioectodermal dysplasia 4; Nephronophthisis 13; Retinitis pigmentosa; Senior-Loken syndrome 8 AD/AR N/A N/A Cardiovascular; Craniofacial; Dental; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal General The conditions can involve multiple congenital anomalies; Renal transplantation has been described Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19430947; 21378380; 22019273; 23559409; 23683095 WDR26 21208 80232 Skraban-Deardorff syndrome AD N/A N/A Craniofacial; Dental; Musculoskeletal; Neurologic General Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28686853 WDR35 29250 57539 Cranioectodermal dysplasia 2; Short -rib thoracic dysplasia 7 with or without polydactyly AR N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Renal General The condition can include cardac defects and renal and hepatic disease, among other findings; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20817137; 21378380; 21473986 WDR37 31406 22884 Neurooculocardiogenitourinary syndrome AD N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31327508; 31327510 WDR4 12756 10785 Galloway-Mowat syndrome 6 AR Pediatric Allelic with Microcephaly, growth deficiency, seizures, and brain malformations (AR) Craniofacial; Endocrine; Neurologic; Renal Endocrine; Renal Endocrine manifestations such as growth hormone deficiency have been observed, and awareness may allow prompt recognition and treatment; Among other features, the condition may include renal disease, and use of immunosuppressive treatments has been described as necessary in at least one patient 26416026; 28617965; 29597095; 30079490 WDR45 28912 11152 Neurodegeneration with brain iron accumulation 5 XL N/A N/A Neurologic General Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21920862; 22892189; 23176820; 23435086; 23447832; 23687123 WDR45B 25072 56270 Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures AR N/A N/A Neurologic General Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21937992; 28503735 WDR62 24502 284403 Microcephaly 2, primary, autosomal recessive, with or without cortical malformations AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10573015; 20729831; 20890279; 20890278; 21496009; 21834044; 21961505; 22308068; 23065275 WDR72 26790 256764 Amelogenesis imperfecta, hypomaturation type, IIA3 AR N/A N/A Dental General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19853237; 22243262; 23293580 WDR73 25928 84942 Galloway-Mowat syndrome AR N/A N/A Neurologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25466283; 25873735; 26123727 WDR81 26600 124997 Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2; Hydrocephalus, nonsyndromic, autosomal recessive 3 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16371500; 21885617; 25558065; 26437881; 28556411 WEE2 19684 494551 Oocyte maturation defect 5 AR N/A N/A Obstetric General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29606300; 30628060 WFS1 12762 7466 Wolfram syndrome 1 AR Pediatric Allelic with Wolfram-like syndrome, autosomal dominant (AD); Deafness, autosomal dominant 6/14/38 (AD); Cataract 41 (AD) Audiologic/Otolaryngologic; Endocrine; Neurologic; Ophthalmologic; Renal Audiologic/Otolaryngologic; Endocrine; Renal A small proportion of individuals may have congenital deafness Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Recognition and interventions related to endocrine anomalies (eg, diabetes insipidus, diabetes mellitus) may be beneficial; Awareness of the possibility of renal anomalies (eg, hydronephrosis) may allow surveillance and management to potentially benefit renal/urologic function 5956444; 8595423; 9817917; 10521293; 11709537; 11317350; 11709538; 12107816; 12181639; 15070927; 16151413; 17568405; 17492394; 18806274; 21823543; 21917145; 21446023; 22238590; 21968327; 22498363; 22226368; 23531866 WHRN 16361 25861 Usher syndrome, type 2D; Deafness, autosomal recessive 31 AR Pediatric Audiologic/Otolaryngologic; Ophthalmologic Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 12833159; 17171570 WIPF1 12736 7456 Wiskott-Aldrich syndrome 2 AR Pediatric Allergy/Immunology/Infectious; Dermatologic; Hematologic Allergy/Immunology/Infectious; Hematologic Individuals have been described with frequent and severe infections (including a lethal infectious course in one individual), and thus, antiinfectious prophylaxis and early and aggressive treatment of infections and bleeding issues may be beneficial; Unrelated CBT has been reported as effective 22231303 WIPI2 32225 26100 Intellectual developmental disorder with short stature and variable skeletal anomalies AR N/A N/A Neurologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30968111 WNK1 14540 65125 Pseudohypoaldosteronism, type IIC; Neuropathy, hereditary sensory and autonomic, type IIA AD/AR Pediatric Neurologic; Renal Neurologic; Renal Treatment (eg, correction of physiologic abnormalities by thiazide diuretics) can be effective, and measures towards optimizing blood pressure can decrease morbidity and mortality related to potential sequale of hypertension; In Neuropathy, hereditary sensory and autonomic, type IIl, reduced pain sensation may result in injury, as well as result in ulceration/infection, and precautions may be beneficial 20323803; 10869238; 11498583; 15060842; 5455397; 15911806; 16946995; 16636245; 16534117; 18521183; 22080857; 22266938; 21768522; 22073419; 22910560; 22934535 WNK4 14544 65266 Pseudohypoaldosteronism, type IIB AD Pediatric Renal Renal Treatment (eg, correction of physiologic abnormalities by thiazide diuretics) can be effective, and measures towards optimizing blood pressure can decrease morbidity and mortality related to potential sequale of hypertension 718349; 718348; 504550; 6103235; 9171836; 11498583; 19016006; 22266938; 22073419 WNT1 12774 7471 Osteoprosis, autosomal dominant; Osteogenesis imperfecta, type XV AD/AR N/A N/A Musculoskeletal General The use of bisphosphonates has been described to treat osteogenesis imperfecta, but it is unclear if an early (genetic) diagnosis would be advantageous Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23434763; 23499309; 23499310; 23656646 WNT10A 13829 80326 Odontoonychodermal dysplasia; Schopf-Schulz-Passarge syndrome; Tooth agenesis, selective, 4 AR N/A N/A Dental; Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 4281327; 6837628; 15316967; 17847007; 19471313; 19559398; 20163410; 20418069; 21143469; 21484994; 21834823; 24449199 WNT10B 12775 7480 Tooth agenesis, selective, 8; Split-hand/foot malformation 6 AD/AR N/A N/A Dental; Dermatologic; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12072797; 18515319; 20635353; 21554266; 27321946; 29427788 WNT2B 12781 7482 Diarrhea 9 AR Pediatric Gastrointestinal Gastrointestinal The condition can involve severe and early-onset diarrhea, and awareness may help with management (eg, via parenteral nutrition, which has been described as necessary) 29909964 WNT3 12782 7473 Tetraamelia syndrome 1 AR N/A N/A Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14872406 WNT4 12783 54361 Mullerian aplasia and hyperandrogenism; 46,XX sex reversal with dysgenesis of kidneys, adrenals, and lungs (SERKAL syndrome) AD/AR N/A N/A Cardiovascular; Endocrine; Genitourinary; Musculoskeletal; Pulmonary; Renal General The conditions can involve multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15317892; 16959810; 18179883; 18182450 WNT5A 12784 7474 Robinow syndrome, autosomal dominant 1 AD N/A N/A Cardiovascular; Craniofacial; Dental; Genitourinary; Musculoskeletal; Renal Renal Individuals have been described with high-grade vesicoureteral reflux, and surveillance and management may be helpful to preserve renal function 5771504; 3746837; 17256787; 19918918; 24716670 WNT7A 12786 7476 Ulna and fibula, absence of, with severe limb deficiency (Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome); Fuhrmann syndrome AR N/A N/A Dermatologic; Genitourinary; Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 7363910; 3981578; 3400735; 3066902; 2338339; 1785629; 9128926; 11332978; 12868468; 16826533; 19309796; 20949531; 21271649; 21344627 WRAP53 25522 55135 Dyskeratosis congenita, autosomal recessive 3 AR Pediatric Dermatologic; Hematologic; Oncologic; Pulmonary Hematologic; Oncologic; Pulmonary Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; Lung transplant may be indicated in individuals with advanced lung diease; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal 21205863; 20301779 WRN 12791 7486 Werner syndrome AR Pediatric Cardiovascular; Craniofacial; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal; Obstetric; Oncologic; Ophthalmologic Cardiovascular; Endocrine; Obstetric; Oncologic Individuals typically have insulin resistance, as well as increased risk of atherosclerosis and malignancy (eg, melanomas, osteosarcomas, sarcomas, and thyroid carcinoma) and and awareness may allow preventive measures related to the risk of atherosclerosis, as well as early diagnosis and treatment of atherosclerosis, diabetes mellitus, and malignancy, which may reduce morbidity and mortality; Awareness and interventions related to endocrine complications (eg, metformin treatment for insulin resistance) as well as the potential for obstetric sequelae (eg, cervical incompetence) may be beneficial in the management of reproductive health 14042963; 7460386; 8722214; 8968742; 8602509; 9048918; 9253306; 9012406; 10220139; 16786514; 17476199; 18205852; 20301687; 20443122; 22654791; 23524889; 23552003; 23849162; 23936869 WT1 12796 7490 Denys-Drash syndrome; Wilms tumor, type 1; Frasier syndrome AD Pediatric Allelic with Meacham syndrome, which involves multiple malformations, but typically does not involve findings such as Wilms tumor (AD); Allelic with Nephrotic syndrome, type 4 (AD), though it is unclear if this disorder typically occurs without oncologic manifestations Cardiovascular; Endocrine; Genitourinary; Oncologic; Renal; Pulmonary Oncologic; Renal Individuals are at risk for several types of neoplasm, and surveillance may allow early detection and treatment for common oncologic features (eg, Wilms tumor, gonadoblastoma); Renal transplant may be indicated (and beneficial) in individuals with end-stage renal faiure 14149008; 4292870; 4316066; 4153449; 331956; 3000666; 3130865; 3026952; 2172500; 1655284; 1338906; 1338905; 8386697; 8071974; 7645607; 7607640; 9398852; 9108089; 9529364; 9607189; 11241056; 12050205; 17853480; 18203154; 18688870; 20150449; 20301471; 21434831; 21559934; 21614510; 22585769; 22876585; 24161391 WWOX 12799 51741 Developmental and epileptic encephalopathy 28; Spinocerebellar ataxia, autosomal recessive 12 AR N/A N/A Neurologic General As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17470496; 24369382; 24456803; 25411445 XDH 12805 7498 Xanthinuria, type I AR Pediatric Biochemical; Musculoskeletal; Renal Biochemical; Renal Dietary measures (eg, purine restricted, increased fluid intake) and medical measures (eg, allopurinol) can be effective 13118765; 861350; 3818951; 3339736; 754557; 9767921; 9153281 XG 12806 7499 XG blood group BG Pediatric Hematologic General Variants associated with a blood group may be important in specific situations (eg, related to transfusion) 7533029 XIAP 592 331 Lymphoproliferative syndrome, X-linked, 2 XL Pediatric Allergy/Immunology/Infectious; Hematologic; Oncologic Allergy/Immunology/Infectious; Hematologic; Oncologic Digenic disease (with CD40LG) have been reported Surveillance for EBV infections is indicated; Prompt recognition and treatment of hemophagocytic lymphohistiocytosis (with immunosuppressive agents or rituximab in the case of EBV infection); Treatment for individuals with hypogammaglobulinemia (with IVIG) may be beneficial; Awareness of the increased risk of lymphoma may allow prompt recognition and treatment; HSCT has been described, and is indicated in many individuals 17080092; 20301580; 21119115; 21543760; 21971331 XIST 12810 7503 X-inactivation, familial skewed, 1 XL N/A N/A General General It has been suggested that the condition may be related to reproductive outcomes, but the evidence is mixed Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 8825575; 9354806; 10090877; 10441596; 15731119; 19646676 XK 12811 7504 McLeod syndrome XL Pediatric Cardiovascular; Hematologic; Musculoskeletal; Neurologic Cardiovascular Surveillance for cardiovascular disease (eg, dilated cardiomyopathy and arrhythmias) and early medical treatment may reduce morbidity 13860532; 8004674; 11261514; 11761473; 17683354; 21463873 XPA 12814 7507 Xeroderma pigmentosum, group A AR Pediatric Dermatologic; Neurologic; Oncologic; Ophthalmologic Dermatologic; Oncologic; Ophthalmologic Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance (primarily related to skin manifestations, as well as other sequelae) can be beneficial 286113; 2168777; 2234061; 1571258; 1372102; 8053698; 9671271; 10447254; 20301571; 20534089; 20574439; 22044607; 22081045 XPC 12816 7508 Xeroderma pigmentosum, group C AR Pediatric Dermatologic; Neurologic; Oncologic; Ophthalmologic Dermatologic; Oncologic; Ophthalmologic Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance (primarily related to skin manifestations, as well as other sequelae) can be beneficial 7389185; 6696469; 8298653; 9804340; 10766188; 11511294; 14662655; 20301571; 21482201; 22211393; 23143338; 23173980; 23436679 XPNPEP2 12823 7512 Angioedema induced by ACE inhibitors, susceptibility to XL Pediatric General Pharmacogenomic Medication selection would be impacted in individuals with relevant variants 16175507 XPNPEP3 28052 63929 Nephronophthisis-like nephropathy 1 AR N/A N/A Audiologic/Otolaryngologic; Neurologic; Renal General Avoidance of nephrotoxic medications may be beneficial Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20179356 XPR1 12827 9213 Basal ganglia calcification, idiopathic, 6 AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 886353; 25938945 XRCC1 12828 7515 Spinocerebellar ataxia, autosomal recessive, 26 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28002403 XRCC2 12829 7516 Fanconi anemia, complementation group U AR N/A Allelic with Premature ovarian failure 17 (AR); Spermatogenic failure 50 (AR) Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic General In individuals with Fanconi anemia, complementation group U, hematologic or oncologic manifestations have not been described Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22232082; 27208205; 30042186; 30489636 XRCC4 12831 7518 Short stature, microcephaly, and endocrine dysfunction AR Pediatric Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Oncologic; Renal Endocrine; Oncologic Endocrine anomalies, including hypergonadotropic hypogonadism, multinodular goiter, and diabetes mellitus have been described, and awareness may allow screening and early management; The condition has been described as including an increased risk of cancer, and awareness may allow early detection and management 24389050; 25728776; 25742519; 25839420; 25872942; 26255102 XYLT1 15516 64131 Desbuquois dysplasia 2 AR N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23982343; 24581741 XYLT2 15517 64132 Spondyloocular syndrome AR N/A N/A Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic; Renal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26027496 YAP1 16262 10413 Ocular coloboma with or without hearing impairment, cleft lip/palate, and/or mental retardation AD Pediatric Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic; Renal Audiologic/Otolaryngologic Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development 24462371 YARS1 12840 8565 Charcot-Marie-Tooth disease, dominant intermediate C AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14606043; 16429158 YARS2 24249 51067 Myopathy, lactic acidosis, and sideroblastic anemia 2 AR Pediatric Cardiovascular; Hematologic; Musculoskeletal Cardiovascular; Hematologic Individuals may develop transfusion-dependent sideroblastic anemia in infancy; Surveillance for cardiovascular manifestations may allow early medical interventions 20598274; 22504945; 24344687; 24430573 YEATS2 25489 55689 Epilepsy, myoclonic, familial adult, 4 AD N/A N/A Neurologic General Reported variants have involved intronic repeat expansions Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22713812; 31539032 YIF1B 30511 90522 Kaya-Barakat-Masson syndrome AR N/A N/A Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 32006098; 33103737 YIPF5 24877 81555 Microcephaly, epilepsy, and diabetes syndrome 2 AR Pediatric Endocrine; Neurologic Endocrine Among other findings, individuals have been described with neonatal-onset, insulin-requiring diabetes mellitus, and awareness may allow prompt recognition and medical management 33164986 YME1L1 12843 10730 Optic atrophy 11 AR N/A N/A Audiologic/Otolaryngologic; Biochemical; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27495975 YWHAG 12852 7532 Developmental and epileptic encephalopathy 56 AD N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28777935 YWHAZ 12855 7534 Popov-Chang syndrome AD N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31024343 YY1 12856 7528 Gabriele-de Vries syndrome (GADEVS) AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28575647 YY1AP1 30935 55249 Grange syndrome AR Pediatric Cardiovascular; Craniofacial; Musculoskeletal; Neurologic Cardiovascular Among other features, individuals have been described with arrhythmias and vascular anomalies, and awareness may allow early diagnosis and management of these issues 9489789; 11241488; 16691574; 27939641; 30556293 ZAP70 12858 7535 Autoimmune disease, multisystem, infantile-onset 2; Immunodeficiency 48 AR Pediatric Allergy/Immunology/Infectious Allergy/Immunology/Infectious In Autoimmune disease, multisystem, infantile-onset 2, individuals may demonstrate multiple autoimmune sequelae that may be refractory to immunosuppressants, and HSCT has been described as effective; In Selective T-cell defect, prophylactic measures, in the short term, include IVIG administration as well as antiinfectious prophylaxis; If blood products are necessary, they should be irradiated and CMV and EBV-negative; Live vaccines should be avoided, and immunizations should be deferred until reconstitution of the immune system; HSCT has been described as effective in some individuals 2511270; 8124727; 8202713; 8202712; 10574909; 10748099; 11123350; 11412303; 11463783; 18509675; 19548248; 20301777; 23124046; 26783323 ZBTB11 16740 27107 Intellectual development disorder, autosomal recessive, 69 AR N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29893856 ZBTB16 12930 7704 Skeletal defects, genital hypoplasia, and mental retardation AR N/A N/A Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11891687; 18611983 ZBTB18 13030 10472 Mental retardation, autosomal dominant 22 AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24193349 ZBTB20 13503 26137 Primrose syndrome AD N/A N/A Craniofacial; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25062845; 25017102; 27061120; 30256248 ZBTB24 21143 9841 Immunodeficiency-Centromeric Instability-Facial Anomalies 2 AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic Allergy/Immunology/Infectious Immunodeficiency-Centromeric Instability-Facial Anomalies may be recognizable due to features including dysmorphic facial features and developmental delay Individuals may demonstrate agammaglobulinemia/hypogammaglobulinemia, resulting in recurrent/severe (including fatal) respiratory and GI infections , and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial in order to decrease morbidity and mortality 21596365; 25055871 ZBTB42 32550 100128927 Lethal congenital contracture syndrome 6 AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25055871 ZC3H14 20509 79882 Mental retardation, autosomal recessive 56 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21734151 ZC4H2 24931 55906 Wieacker-Wolff syndrome; Wieacker-Wolff syndrome, female-restricted XL N/A N/A Craniofacial; Genitourinary; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23623388; 26056227; 28345801; 31206972 ZCCHC8 25265 55596 Pulmonary fibrosis and/or bone marrow failure, telomere-related, 5 AD Adult Hematologic; Pulmonary Hematologic; Pulmonary Surveillance and prompt treatment of bone marrow failure may reduce morbidity; For treatment related to pulmonary fibrosis, early recognition may allow prompt medical management 31488579 ZDHHC15 20342 158866 Mental retardation, X-linked 91 XL N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 15915161 ZDHHC9 18475 51114 Intellectual developmental disorder, X-linked syndromic, Raymond type XL N/A N/A Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 17436253; 19377476 ZEB1 11642 6935 Corneal dystrophy, Fuchs endothelial 6; Corneal dystrophy, posterior polymorphous, 3 AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12654361; 16252232; 20036349; 21067486; 22199242; 23599324; 23662738; 23807282; 26622166 ZEB2 14881 9839 Mowat-Wilson syndrome AD N/A N/A Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic General The condition can include Hirschsprung disease, among other multi-systemic manifestations; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9719364; 11448942; 11279515; 14679597; 15121779; 16088920; 16688751; 16532472; 17203459; 19215041;20301585; 21343952; 21497296; 22246645; 22486326; 23322667; 23427518; 23466526; 23523603; 24029077; 24715670; 27831545 ZFHX2 20152 85446 Marsili syndrome AD N/A N/A Neurologic General Insensitivity to pain can result in injuries Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29253101 ZFP57 18791 346171 Diabetes mellitus, transient neonatal, 1 AD Pediatric Endocrine Endocrine The pathogenesis can involve imprinting defects (eg, paternal UPD, paternal duplication, methylation defects) Individuals present early in life with failure to thrive, hyperglycemia, and dehydration, and prompt recognition and treatment can reduce morbidity 18622393 ZFPM2 16700 23414 46,XY sex reversal 9 AD Pediatric Allelic with Diaphragmatic hernia 3 (AD); Tetralogy of Fallot (AD) Cardiovascular; Genitourinary; Musculoskeletal; Neurologic; Pulmonary Oncologic Individuals may be at risk for gonadal tumors, and awareness may allow preventive measures and early management 14517948; 16103912; 17568391; 20807224; 24549039; 24702427; 25996639; 29018978; 29264446; 29536580; 31028076; 31962012 ZFYVE26 20761 23503 Spastic paraplegia 15 AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 11342696; 14745065; 17661097; 19438933; 18394578; 19805727 ZFYVE27 26559 118813 Spastic paraplegia 33, autosomal dominant AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16826525; 18606302 ZIC1 12872 7545 Craniosynostosis 6; Structural brain anomalies with impaired intellectual development and craniosynostosis AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 26340333; 30391508 ZIC2 12873 7546 Holoprosencephaly 5 AD N/A N/A Endocrine; Neurologic General Individuals with holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 9771712; 11285244; 19955556; 20104608 ZIC3 12874 7547 Congenital heart defects, nonsyndromic, 1, X-linked; Heterotaxy, visceral, 1, X-linked; VACTERL association, X-linked, with or without hydrocephalus XL N/A N/A Cardiovascular; Genitourinary; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary; Renal General The condition can include structural heart anomalies as well as other manifestations; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 3674105; 9354794; 10980576; 14681828; 17295247; 20452998; 21465648; 21864452; 23427188; 24123890 ZIM2 12875 23619 Schizophrenia AD N/A N/A Neurologic General Evidence or clinical applicability unclear 21743468 ZMIZ1 16493 57178 Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies AD N/A N/A Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 30639322 ZMPSTE24 12877 10269 Mandibuloacral dysplasia with type B lipodystrophy; Restrictive dermopathy, lethal AD/AR N/A N/A Dental; Dermatologic; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 1642279; 12913070; 15317753; 16297189; 15843403; 18435794; 19504603; 20034068; 22495976 ZMYND10 19412 51364 Ciliary dyskinesia, primary, 22 AR Pediatric Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary The condition can involve multiple anomalies, and individuals may require surgery or other interventions related to findings such as congenital cardiac malformations Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary 20301301; 23891469; 23891471 ZMYND11 16966 10771 Mental retardation, autosomal domianant, 30 AD N/A N/A Craniofacial; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25217958 ZMYND15 20997 84225 Spermatogenic failure 14 AR N/A N/A Genitourinary General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24431330 ZNF141 12926 7700 Postaxial polydactyly type A, autosomal recessive AR N/A N/A Musculoskeletal General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23160277 ZNF142 12927 7701 Neurodevelopmental disorder with impaired speech and hyperkinetic movements AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31036918 ZNF148 12933 7707 Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies (GDACCF) AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal General The condition can include multiple congenital anomalies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 27964749 ZNF292 18410 23036 Intellectual developmental disorder, autosomal dominant 64 AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 31723249 ZNF335 15807 63925 Microcephaly 10, primary, autosomal recessive AR N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 23178126 ZNF341 15992 84905 Hyper-IgE recurrent infection syndrome 3, autosomal recessive AR Pediatric Allergy/Immunology/Infectious; Craniofacial; Neurologic Allergy/Immunology/Infectious Individuals have been described with susceptibility to recurrent bacterial and fungal infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial in order to decrease morbidity and mortality 29907690; 29907691 ZNF408 20041 79797 Exudative vitreoretinopathy 6; Retinitis pigmentosa 72 AD/AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 6897033; 23716654; 25882705 ZNF41 13107 7592 Mental retardation, X-linked 89 XL N/A N/A Neurologic General The evidence of variants as being related to disease causation has been questioned due to subsequent population-based studies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 14628291; 23871722 ZNF423 16762 23090 Joubert syndrome 19; Nephronophthisis 14 AD/AR N/A N/A Neurologic; Ophthalmologic; Pulmonary; Renal General The conditions can involve manifestations including renal disease and anomalous perinatal breathing Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 22863007 ZNF462 21684 58499 Weiss-Kruszka syndrome AD N/A N/A Cardiovascular; Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28513610; 31361404 ZNF469 23216 84627 Brittle cornea syndrome 1 AR Pediatric Musculoskeletal; Ophthalmologic Ophthalmologic Individuals are prone to ophthalmologic injury (such as corneal rupture) with minimal trauma, and protective measures may be beneficial 13627089; 14218178; 5755738; 4872990; 5775573; 4691558; 962660; 7387950; 2112090; 2363420; 14679583; 18452888; 19661234; 20938016 ZNF480 23305 147657 Schizophrenia AD N/A N/A Neurologic General Evidence or clinical applicability unclear 21743468 ZNF513 26498 130557 Retinitis pigmentosa 58 AR N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 20797688; 20227676 ZNF565 26726 147929 Schizophrenia AD N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21743468 ZNF592 28986 9640 Spinocerebellar ataxia, autosomal recessive 5 AR N/A N/A Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 12030328; 20531441 ZNF644 29222 84146 Myopia 21, autosomal dominant AD N/A N/A Ophthalmologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 21695231 ZNF674 17625 641339 Mental retardation, X-linked 92 XL N/A N/A Neurologic General The evidence of variants as being related to disease causation has been questioned due to subsequent population-based studies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16385466; 23871722 ZNF687 29277 57592 Paget disease of bone 6 AD Adult Musculoskeletal; Oncologic Oncologic The condition can involve malignant giant cell tumors (GCT) of the bone arising from within the Paget bone lesions, and awareness may allow early detection and management 26849110 ZNF711 13128 7552 Mental retardation, X-linked 97 XL N/A N/A Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 19377476 ZNF750 25843 79755 Seborrhea-like dermatitis with psoriasiform elements AD N/A N/A Dermatologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 16751772 ZNF81 13156 347344 Mental retardation, X-linked 45 XL N/A N/A Craniofacial; Musculoskeletal; Neurologic General The evidence of variants as being related to disease causation has been questioned due to subsequent population-based studies Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 10398246; 15121780; 23871722 ZNHIT3 12309 9326 PEHO syndrome AR N/A N/A Craniofacial; Dermatologic; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28335020 ZP1 13187 22917 Oocyte maturation defect 1 AR N/A N/A Obstetric General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 24670168 ZP2 13188 7783 Oocyte maturation defect 6 AR N/A N/A Obstetric General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 29895852 ZP3 13189 7784 Oocyte maturation defect 3 AD N/A N/A Obstetric General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 28886344 ZPR1 13051 8882 Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies AR Pediatric Audiologic/Otolaryngologic; Craniofacial; Dental; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Renal Audiologic/Otolaryngologic; Renal Among other findings, the condition can involve hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; As the condition can include renal anomalies, with morbidity and mortality reported to involve uremia, awareness may allow early interventions related to these manifestations 29851065 ZSWIM6 29316 57688 Acromelic frontonasal dysostosis; Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features AD N/A N/A Craniofacial; Musculoskeletal; Neurologic General Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing 25105228; 29198722