Infantile spasms

Summary

Infantile spasms (MONDO:0018097) is a disease (an umbrella term covering 8 Mondo subtypes) with 22 cohort genes and 27 clinical trials. The dominant Reactome pathway is Interaction between L1 and Ankyrins (4 cohort genes). Top therapeutic interventions include prednisolone, corticotropin, and vigabatrin.

At a glance

• Umbrella term: 8 Mondo subtypes
• Cohort genes: 22
• ClinVar variants: 46
• Phenotypes (HPO): 6
• Clinical trials: 27

Clinical features

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0001336	Myoclonus	Very frequent (80-99%)
HP:0002376	Developmental regression	Very frequent (80-99%)
HP:0002521	Hypsarrhythmia	Very frequent (80-99%)
HP:0012469	Infantile spasms	Very frequent (80-99%)
HP:0000707	Abnormality of the nervous system	Frequent (30-79%)
HP:0011121	Abnormal skin morphology	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	infantile spasms
Mondo ID	MONDO:0018097
Orphanet	3451, 697160
DOID	DOID:0050562
ICD-11	1023597213
NCIT	C84788
SNOMED CT	28055006
UMLS	C0037769
MedGen	11519
GARD	0007887
MedDRA	10021750
NORD	1848
Is cancer (heuristic)	no

Also known as: IESS · infantile epileptic spasms syndrome · infantile spasms · infantile spasms syndrome · intellectual disability-hypsarrhythmia syndrome · tonic spasms with clustering, arrest of psychomotor development and hypsarrhythmia on EEG · West syndrome · West’s syndrome · X-linked infantile spasm syndrome · X-linked infantile spasms

Data availability: 46 ClinVar variants · 16 GenCC gene-disease records · 7 cell lines.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › infantile spasms

Related subtypes (1183): Neu-Laxova syndrome, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, syndromic intellectual disability, abdominal obesity-metabolic syndrome, fibrogenesis imperfecta ossium, Fanconi renotubular syndrome, palindromic rheumatism, hepatorenal syndrome, Potter sequence, vertebral artery insufficiency, sick sinus syndrome, Tietze syndrome, toxic shock syndrome, capillary leak syndrome, dumping syndrome, FG syndrome, basilar artery insufficiency, long QT syndrome, Treacher-Collins syndrome, superior mesenteric artery syndrome, disappearing bone disease, Brown-Sequard syndrome, Froelich syndrome, diffuse infiltrative lymphocytosis syndrome, Capgras syndrome, compartment syndrome, central sleep apnea syndrome, irritable bowel syndrome, nephrotic syndrome, myalgic encephalomeyelitis/chronic fatigue syndrome, acute coronary syndrome, fibromyalgia, substance withdrawal syndrome, acute chest syndrome, Barre-Lieou syndrome, cauda equina syndrome, Kluver-Bucy syndrome, Miller Fisher syndrome, persian gulf syndrome, Reye syndrome, thoracic outlet syndrome, Waterhouse-Friderichsen syndrome, Wissler syndrome, acute respiratory distress syndrome, Achenbach syndrome, miliaria, anterior spinal artery syndrome, burning mouth syndrome, dry eye syndrome, empty sella syndrome, euthyroid sick syndrome, lateral medullary syndrome, subclavian steal syndrome, tarsal tunnel syndrome, tethered spinal cord syndrome, branchio-oto-renal syndrome, prune belly syndrome, Achard syndrome, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, Finnish type amyloidosis, Angelman syndrome, aniridia-absent patella syndrome, ankyloblepharon filiforme adnatum-cleft palate syndrome, Townes-Brocks syndrome, obstructive sleep apnea syndrome, Lown-Ganong-Levine syndrome, Behcet disease, brachydactyly-arterial hypertension syndrome, brachydactyly type A2, fibular aplasia-ectrodactyly syndrome, brachydactyly-nystagmus-cerebellar ataxia syndrome, Sillence syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, dilated cardiomyopathy 1A, cat-eye syndrome, cerebrocostomandibular syndrome, Alagille syndrome, autosomal dominant chondrodysplasia punctata, cleidocranial dysplasia 1, cleidorhizomelic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Cri-du-chat syndrome, autosomal dominant deafness - onychodystrophy syndrome, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, Duane retraction syndrome, 3-M syndrome, dyschondrosteosis-nephritis syndrome, hereditary benign intraepithelial dyskeratosis, encephalopathy, recurrent, of childhood, Camurati-Engelmann disease, Felty syndrome, chromosome 16p12.1 deletion syndrome, 520kb, Frasier syndrome, Gamstorp-Wohlfart syndrome, Tourette syndrome, glaucoma-sleep apnea syndrome, renal cysts and diabetes syndrome, hypotrichosis-lymphedema-telangiectasia syndrome (grouping), GMS syndrome, gray platelet syndrome, hand-foot-genital syndrome, facial hemiatrophy, Bencze syndrome, alpha thalassemia-intellectual disability syndrome type 1, Gilbert syndrome, mullerian duct anomalies-limb anomalies syndrome, hypoparathyroidism-deafness-renal disease syndrome, chromosome 18p deletion syndrome, Pallister-Hall syndrome, ichthyosis-cheek-eyebrow syndrome, Jacobsen syndrome, palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome, palmoplantar keratoderma-esophageal carcinoma syndrome, Kleine-Levin syndrome, angioosteohypertrophic syndrome, congenital laryngeal web, Lenz-Majewski hyperostotic dwarfism, Noonan syndrome with multiple lentigines, lymphedema-cerebral arteriovenous anomaly syndrome, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, yellow nail syndrome, lymphedema-distichiasis syndrome, Nager acrofacial dysostosis, jaw-winking syndrome, Marfan syndrome, Melkersson-Rosenthal syndrome, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, microgastria-limb reduction defect syndrome, Mobius syndrome, muscular atrophy-ataxia-retinitis pigmentosa-diabetes mellitus syndrome, nail-patella syndrome, Schilbach-Rott syndrome, syndromic orbital border hypoplasia, Buschke-Ollendorff syndrome, nasopalpebral lipoma-coloboma syndrome, Perry syndrome, Poland syndrome, polydactyly-myopia syndrome, Greig cephalopolysyndactyly syndrome, Prader-Willi syndrome, Guttmacher syndrome, Currarino triad, Hutchinson-Gilford progeria syndrome, progeria-short stature-pigmented nevi syndrome, Liddle syndrome, exfoliation syndrome, ptosis-strabismus-ectopic pupils syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, radial ray hypoplasia-choanal atresia syndrome, Roussy-Levy syndrome, Silver-Russell syndrome, Ruvalcaba syndrome, oculodental syndrome, Rutherfurd type, aplasia of lacrimal and salivary glands, scalp defects-postaxial polydactyly syndrome, ulnar-mammary syndrome, septooptic dysplasia, Czeizel-Losonci syndrome, polycystic ovary syndrome, stiff-person syndrome, syndactyly-polydactyly-ear lobe syndrome, HELLP syndrome, double uterus-hemivagina-renal agenesis syndrome, VACTERL/vater association, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, ptosis-vocal cord paralysis syndrome, Freeman-Sheldon syndrome, Williams syndrome, Denys-Drash syndrome, Wolf-Hirschhorn syndrome, ablepharon macrostomia syndrome, acrocallosal syndrome, PAGOD syndrome, alopecia - intellectual disability syndrome, mitochondrial DNA depletion syndrome 4a, Alstrom syndrome, aniridia-cerebellar ataxia-intellectual disability syndrome, aniridia-renal agenesis-psychomotor retardation syndrome, aplasia cutis congenita-intestinal lymphangiectasia syndrome, fetal akinesia deformation sequence, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, Bloom syndrome, Elsahy-Waters syndrome, campomelia, Cumming type, camptomelic syndrome, long-limb type, congenital cataract-ichthyosis syndrome, colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, hepatic fibrosis-renal cysts-intellectual disability syndrome, Charcot-Marie-Tooth disease-hearing loss-intellectual disability syndrome, CHARGE syndrome, Aagenaes syndrome, infantile choroidocerebral calcification syndrome, Yunis-Varon syndrome, corneal dystrophy-perceptive deafness syndrome, cortical blindness-intellectual disability-polydactyly syndrome, Crigler-Najjar syndrome, cataract-nephropathy-encephalopathy syndrome, Fraser syndrome, cystic fibrosis-gastritis-megaloblastic anemia syndrome, cystinuria, DOORS syndrome, high myopia-sensorineural deafness syndrome, dermochondrocorneal dystrophy, nephrogenic diabetes insipidus-intracranial calcification syndrome, diverticulosis of bowel, hernia, and retinal detachment, Dyggve-Melchior-Clausen disease, cerebellar ataxia, intellectual disability, and dysequilibrium, ectrodactyly-polydactyly syndrome, Bonnemann-Meinecke-Reich syndrome, epidermolysis bullosa simplex 5B, with muscular dystrophy, Wolcott-Rallison syndrome, ermine phenotype, eyebrow duplication-syndactyly syndrome, Fanconi-like syndrome, gingival fibromatosis-facial dysmorphism syndrome, frontofacionasal dysplasia, Fryns syndrome, German syndrome, Bernard-Soulier syndrome, triple-A syndrome, Grubben-de Cock-Borghgraef syndrome, mullerian derivatives-lymphangiectasia-polydactyly syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Hirschsprung disease-nail hypoplasia-dysmorphism syndrome, Holzgreve-Wagner-Rehder syndrome, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, growth delay-hydrocephaly-lung hypoplasia syndrome, Dubin-Johnson syndrome, ornithine translocase deficiency, acrofrontofacionasal dysostosis 2, hypertrichotic osteochondrodysplasia Cantu type, hypergonadotropic hypogonadism-cataract syndrome, primary hypergonadotropic hypogonadism-partial alopecia syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, hypospadias-intellectual disability, Goldblatt type syndrome, Bamforth-Lazarus syndrome, ichthyosis-hepatosplenomegaly-cerebellar degeneration syndrome, ichthyosis-intellectual disability-dwarfism-renal impairment syndrome, Vici syndrome, channelopathy-associated congenital insensitivity to pain, autosomal recessive, Joubert syndrome with oculorenal defect, oculocerebrofacial syndrome, Kaufman type, Landau-Kleffner syndrome, laryngo-onycho-cutaneous syndrome, Laurence-Moon syndrome, Donohue syndrome, Miller-Dieker lissencephaly syndrome, Marinesco-Sjogren syndrome, Frank-Ter Haar syndrome, Mietens syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, microcephalic primordial dwarfism, Toriello type, Say-Barber-Miller syndrome, microcephaly and chorioretinopathy 1, Galloway-Mowat syndrome, microtia with meatal atresia and conductive deafness, mucopolysaccharidosis type 6, mulibrey nanism, lethal multiple pterygium syndrome, lethal congenital contracture syndrome 1, Schwartz-Jampel syndrome, Nathalie syndrome, nephronophthisis 1, nephropathy - deafness - hyperparathyroidism syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, Netherton syndrome, Norman-Roberts syndrome, cloacal exstrophy, ichthyosis-oral and digital anomalies syndrome, Primrose syndrome, familial osteodysplasia, Anderson type, multicentric osteolysis, nodulosis, and arthropathy, osteopenia-intellectual disability-sparse hair syndrome, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, Parana hard-skin syndrome, PEHO syndrome, Imerslund-Grasbeck syndrome, Peters plus syndrome, pili torti-developmental delay-neurological abnormalities syndrome, Rabson-Mendenhall syndrome, postaxial acrofacial dysostosis, Gitelman syndrome, Wiedemann-Rautenstrauch syndrome, Acrootoocular syndrome, holoprosencephaly-postaxial polydactyly syndrome, autosomal recessive multiple pterygium syndrome, Perlman syndrome, retinitis pigmentosa-intellectual disability-deafness-hypogenitalism syndrome, EEC syndrome, SHORT syndrome, Sjogren syndrome, spastic tetraplegia-retinitis pigmentosa-intellectual disability syndrome, corneal-cerebellar syndrome, spastic ataxia-corneal dystrophy syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, familial infantile bilateral striatal necrosis, subaortic stenosis-short stature syndrome, thrombocytopenia-absent radius syndrome, thyrocerebrorenal syndrome, Pendred syndrome, VACTERL with hydrocephalus, Weaver syndrome, Werner syndrome, Wernicke-Korsakoff syndrome, wooly hair-hypotrichosis-everted lower lip-outstanding ears syndrome, de Sanctis-Cacchione syndrome, corpus callosum agenesis-abnormal genitalia syndrome, Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome, X-linked lissencephaly with abnormal genitalia, X-linked myotubular myopathy-abnormal genitalia syndrome, Christianson syndrome, Armfield syndrome, Lesch-Nyhan syndrome, Atkin-Flaitz syndrome, alpha-thalassemia-myelodysplastic syndrome, deafness-intellectual disability, Martin-Probst type syndrome, fragile X-associated tremor/ataxia syndrome, fragile X syndrome, syndactyly-telecanthus-anogenital and renal malformations syndrome, X-linked dominant chondrodysplasia, Chassaing-Lacombe type, X-linked central congenital hypothyroidism with late-onset testicular enlargement, Meester-Loeys syndrome, Arts syndrome, X-linked mandibulofacial dysostosis, Abruzzo-Erickson syndrome, Aicardi syndrome, craniofrontonasal syndrome, deafness-hypogonadism syndrome, X-linked corneal dermoid, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, hydrocephaly-cerebellar agenesis syndrome, keratosis follicularis-dwarfism-cerebral atrophy syndrome, laryngeal abductor paralysis-intellectual disability syndrome, oculocerebrorenal syndrome, Menkes disease, paraplegia-intellectual disability-hyperkeratosis syndrome, mucopolysaccharidosis type 2, orofaciodigital syndrome I, otopalatodigital syndrome type 1, Pallister-W syndrome, Rett syndrome, SCARF syndrome, Simpson-Golabi-Behmel syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, trigonocephaly-short stature-developmental delay syndrome, ulnar hypoplasia-split foot syndrome, van den Bosch syndrome, Wildervanck syndrome, Kearns-Sayre syndrome, MELAS syndrome, MERRF syndrome, Pearson syndrome, proximal tubulopathy-diabetes mellitus-cerebellar ataxia syndrome, pancreatic hypoplasia-diabetes-congenital heart disease syndrome, chondrodysplasia-pseudohermaphroditism syndrome, Qazi Markouizos syndrome, familial developmental dysphasia, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, CODAS syndrome, lethal hemolytic anemia-genital anomalies syndrome, HEC syndrome, anophthalmia plus syndrome, infundibulopelvic stenosis-multicystic kidney syndrome, Ayme-Gripp syndrome, dilated cardiomyopathy 1E, diaphragmatic defect-limb deficiency-skull defect syndrome, skeletal dysplasia-epilepsy-short stature syndrome, Potocki-Shaffer syndrome, amelia cleft lip palate hydrocephalus iris coloboma, human HOXA1 syndromes, dyssegmental dysplasia-glaucoma syndrome, lung agenesis-heart defect-thumb anomalies syndrome, tetrasomy 12p, chromosome 18q deletion syndrome, lymphedema-atrial septal defects-facial changes syndrome, infantile convulsions and choreoathetosis, RHYNS syndrome, Pierre Robin sequence with pectus excavatum and rib and scapular anomalies, colobomatous macrophthalmia-microcornea syndrome, Marshall-Smith syndrome, distal monosomy 13q, MPI-congenital disorder of glycosylation, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, radioulnar synostosis-microcephaly-scoliosis syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type, complex regional pain syndrome type 1, temtamy preaxial brachydactyly syndrome, Diamond-Blackfan anemia 2, genitopatellar syndrome, Phelan-McDermid syndrome, hypotonia-cystinuria syndrome, DNA ligase IV deficiency, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome, Duane-radial ray syndrome, psoriatic arthritis, neonatal ichthyosis-sclerosing cholangitis syndrome, skin fragility-woolly hair-palmoplantar keratoderma syndrome, tubulointerstitial nephritis and uveitis syndrome, caudal duplication, sweet syndrome, ichthyosis prematurity syndrome, Meacham syndrome, BNAR syndrome, PCWH syndrome, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, B-cell immunodeficiency, distal limb anomalies, and urogenital malformations, MEDNIK syndrome, Cerebrorenodigital syndrome, fetal valproate syndrome, Goldberg-Shprintzen syndrome, Al-Gazali syndrome, CEDNIK syndrome, osteosclerosis-ichthyosis-premature ovarian failure syndrome, cortical dysplasia-focal epilepsy syndrome, DK1-congenital disorder of glycosylation, Potocki-Lupski syndrome, Pitt-Hopkins syndrome, XFE progeroid syndrome, deafness-infertility syndrome, COG1-congenital disorder of glycosylation, autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, microtia-eye coloboma-imperforation of the nasolacrimal duct syndrome, mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria, ANE syndrome, CLOVES syndrome, Hirschsprung disease-ganglioneuroblastoma syndrome, parkinsonism-dystonia, infantile, alpha 1-antitrypsin deficiency, COG5-congenital disorder of glycosylation, chromosome 13q14 deletion syndrome, deafness-lymphedema-leukemia syndrome, microcephaly-capillary malformation syndrome, EDICT syndrome, peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, IMAGe syndrome, short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, microcephalic primordial dwarfism, Alazami type, intellectual disability-strabismus syndrome, estrogen resistance syndrome, Hartsfield-Bixler-Demyer syndrome, severe dermatitis-multiple allergies-metabolic wasting syndrome, alacrima, achalasia, and intellectual disability syndrome, familial episodic pain syndrome with predominantly lower limb involvement, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome, retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome, polyendocrine-polyneuropathy syndrome, chronic atrial and intestinal dysrhythmia, motor developmental delay due to 14q32.2 paternally expressed gene defect, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, epilepsy with myoclonic atonic seizures, short stature, microcephaly, and endocrine dysfunction, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, PMP22-RAI1 contiguous gene duplication syndrome, acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome, familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, Luscan-Lumish syndrome, even-plus syndrome, MIRAGE syndrome, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, intellectual disability-epilepsy-extrapyramidal syndrome, 48,XXYY syndrome, FRAXF syndrome, complex hereditary spastic paraplegia, aniridia-ptosis-intellectual disability-familial obesity syndrome, aniridia - intellectual disability syndrome, ankyloblepharon filiforme-imperforate anus syndrome, pentasomy X, Bardet-Biedl syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, Bartter syndrome, arachnodactyly-intellectual disability-dysmorphism syndrome, ataxia-photosensitivity-short stature syndrome, Brugada syndrome, Feingold syndrome, cardiomyopathy-cataract-hip spine disease syndrome, cataract - microcornea syndrome, autism-facial port-wine stain syndrome, cataract-intellectual disability-anal atresia-urinary defects syndrome, cataract-deafness-hypogonadism syndrome, syndromic craniosynostosis, drug rash with eosinophilia and systemic symptoms, multicentric reticulohistiocytosis, hereditary sensory and autonomic neuropathy with deafness and global delay, craniofacial microsomia, ring chromosome 10, Coffin-Siris syndrome, corpus callosum agenesis-double urinary collecting system syndrome, short rib-polydactyly syndrome, oromandibular-limb anomalies syndrome, hemophagocytic syndrome, cataract-glaucoma syndrome, diencephalic syndrome, hypereosinophilic syndrome, distal trisomy 14q, intellectual disability-cataracts-kyphosis syndrome, progressive familial intrahepatic cholestasis, thoraco-abdominal enteric duplication, oculomaxillofacial dysostosis, growth hormone insensitivity syndrome, syndromic dyslipidemia, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, epiphyseal dysplasia-hearing loss-dysmorphism syndrome, eosinophilic granulomatosis with polyangiitis, axial mesodermal dysplasia spectrum, fetal hydantoin syndrome, vitamin K-antagonist embryofetopathy, fetal alcohol syndrome, methimazole embryofetopathy, Evans syndrome, Cornelia de Lange syndrome, cleft lip-retinopathy syndrome, cleft lip/palate-deafness-sacral lipoma syndrome, Crandall syndrome, syndromic microphthalmia, Cole-Carpenter syndrome, myotonic syndrome, Guillain-Barre syndrome, atypical hemolytic-uremic syndrome, Hennekam syndrome, Hernández-Aguirre Negrete syndrome, nodular neuronal heterotopia, Hirschsprung disease-type D brachydactyly syndrome, holoprosencephaly, hydrocephalus-obesity-hypogonadism syndrome, hydrocephalus-blue sclerae-nephropathy syndrome, xeroderma pigmentosum-Cockayne syndrome complex, Joubert syndrome with ocular defect, hypogonadism-mitral valve prolapse-intellectual disability syndrome, hypogonadotropic hypogonadism-retinitis pigmentosa syndrome, hypotrichosis-intellectual disability, Lopes type, congenital ichthyosis-microcephalus-tetraplegia syndrome, Hughes-Stovin syndrome, heart-hand syndrome, ptosis-upper ocular movement limitation-absence of lacrimal punctum syndrome, syndromic agammaglobulinemia, isotretinoin syndrome, microcornea-posterior megalolenticonus-persistent fetal vasculature-coloboma syndrome, Kabuki syndrome, Kenny-Caffey syndrome, muscular pseudohypertrophy-hypothyroidism syndrome, Kousseff syndrome, limb body wall complex, Lennox-Gastaut syndrome, Lowe-Kohn-Cohen syndrome, macrocephaly-short stature-paraplegia syndrome, primary ciliary dyskinesia, familial intestinal malrotation-facial anomalies syndrome, primary hypertrophic osteoarthropathy, Melhem-Fahl syndrome, lower limb deficiency-hypospadias syndrome, 8p23.1 microdeletion syndrome, sickle cell-beta-thalassemia disease syndrome, sickle cell-hemoglobin c disease syndrome, sickle cell-hemoglobin d disease syndrome, sickle cell-hemoglobin E disease syndrome, hereditary persistence of fetal hemoglobin-sickle cell disease syndrome, microcephaly-brain defect-spasticity-hypernatremia syndrome, microcephaly-microcornea syndrome, Seemanova type, Meier-Gorlin syndrome, Mikati-Najjar-Sahli syndrome, shoulder and girdle defects-familial intellectual disability syndrome, myopathy-growth delay-intellectual disability-hypospadias syndrome, Fuchs heterochromic iridocyclitis, microcephalic osteodysplastic primordial dwarfism types I and III, osteochondrodysplatic nanism-deafness-retinitis pigmentosa syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, oculo-skeletal-renal syndrome, olivopontocerebellar atrophy-deafness syndrome, Opitz G/BBB syndrome, imperforate oropharynx-costo vetebral anomalies syndrome, Bruck syndrome, osteoporosis-macrocephaly-blindness-joint hyperlaxity syndrome, calciphylaxis, recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome, X-linked ichthyosis syndrome, autoimmune polyendocrinopathy, renal caliceal diverticuli-deafness syndrome, tempi syndrome, syndromic oculocutaneous albinism, short stature-deafness-neutrophil dysfunction-dysmorphism syndrome, congenital varicella syndrome, polyneuropathy-intellectual disability-acromicria-premature menopause syndrome, celiac trunk compression syndrome, hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome, fetal cytomegalovirus syndrome, Reunion island Larsen syndrome, 46,XX disorder of sex development-anorectal anomalies syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Baraitser-Winter cerebrofrontofacial syndrome, mirror polydactyly-vertebral segmentation-limbs defects syndrome, intellectual disability-hypotonia-skin hyperpigmentation syndrome, congenital hereditary facial paralysis-variable hearing loss syndrome, intellectual disability-microcephaly-phalangeal-facial abnormalities syndrome, Mayer-Rokitansky-Kuster-Hauser syndrome, developmental and speech delay due to SOX5 deficiency, Spigelian hernia-cryptorchidism syndrome, autosomal recessive leukoencephalopathy-ischemic stroke-retinitis pigmentosa syndrome, severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, X-linked spasticity-intellectual disability-epilepsy syndrome, spina bifida-hypospadias syndrome, hantavirus pulmonary syndrome, white matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome, deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome, hearing loss-familial salivary gland insensitivity to aldosterone syndrome, multiple synostoses syndrome, central nervous system calcification-deafness-tubular acidosis-anemia syndrome, multiple paragangliomas associated with polycythemia, syngnathia multiple anomalies, Takayasu arteritis, severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency, spondylocostal dysostosis-hypospadias-intellectual disability syndrome, hypotrichosis-deafness syndrome, thalidomide embryopathy, trisomy X, trisomy 13, trisomy 18, umbilical cord ulceration-intestinal atresia syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, Waardenburg syndrome, Weill-Marchesani syndrome, Wolfram syndrome, epidermal nevus syndrome, digital anomalies-intellectual disability-short stature syndrome, intellectual disability-obesity-brain malformations-facial dysmorphism syndrome, Erdheim-Chester disease, Stevens-Johnson syndrome, CADDS, finger hyperphalangy - toe anomalies - severe pectus excavatum syndrome, ataxia - telangiectasia variant, growth retardation-mild developmental delay-chronic hepatitis syndrome, primary microcephaly-mild intellectual disability-young-onset diabetes syndrome, ferro-cerebro-cutaneous syndrome, dystonia-aphonia syndrome, microcephaly-complex motor and sensory axonal neuropathy syndrome, X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome, severe intellectual disability-hypotonia-strabismus-coarse face-planovalgus syndrome, intrauterine growth restriction-short stature-early adult-onset diabetes syndrome, pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa, familial chylomicronemia syndrome, caudal regression-sirenomelia spectrum, visceral heterotaxy, Holmes-Adie syndrome, microcephalic primordial dwarfism due to RTTN deficiency, Joubert syndrome, congenital generalized hypercontractile muscle stiffness syndrome, Kallmann syndrome, Caroli syndrome, X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability, microlissencephaly-micromelia syndrome, branchiootic syndrome, Plummer-Vinson syndrome, Cushing syndrome, McCune-Albright syndrome, Meckel syndrome, SUNCT syndrome, mucopolysaccharidosis type 3, mucopolysaccharidosis type 4, congenital myasthenic syndrome, Loeys-Dietz syndrome, Alport syndrome, schisis association, Tolosa-Hunt syndrome, iridocorneal endothelial syndrome, Noonan syndrome, short fifth metacarpals-insulin resistance syndrome, progressive supranuclear palsy, benign exophthalmos syndrome, Sandifer syndrome, global developmental delay-osteopenia-ectodermal defect syndrome, tubular renal disease-cardiomyopathy syndrome, angioosteohypotrophic syndrome, 6q terminal deletion syndrome, Axenfeld-Rieger syndrome, peroxisome biogenesis disorder, ectodermal dysplasia syndrome, Seckel syndrome, Sotos syndrome, Stickler syndrome, pelvis syndrome, Susac syndrome, ischio-vertebral syndrome, BRESEK syndrome, Turner syndrome, Usher syndrome, obesity-colitis-hypothyroidism-cardiac hypertrophy-developmental delay syndrome, CREST syndrome, Sheehan syndrome, polymyalgia rheumatica, autoinflammatory syndrome, neuroleptic malignant syndrome, pituitary stalk interruption syndrome, monosomy 13q34, ring chromosome 13, 48,XXXY syndrome, 49,XXXXY syndrome, hereditary continuous muscle fiber activity, Eisenmenger syndrome, Robinow syndrome, Ehlers-Danlos syndrome, hypoplastic right heart syndrome, shone complex, 48,XYYY syndrome, subcortical band heterotopia, complex regional pain syndrome type 2, faciodigitogenital syndrome, neoplastic syndrome, paraneoplastic syndrome, post-infectious syndrome, Achard-Thiers syndrome, acral dysostosis dyserythropoiesis syndrome, agnathia-microstomia-synotia, Aksu von Stockhausen syndrome, Aloi Tomasini Isaia syndrome, temporomandibular joint dysfunction syndrome, Apert-like polydactyly syndrome, arakawa syndrome 2, arena syndrome, Arnold stickler bourne syndrome, baetz-greenwalt syndrome, bagatelle Cassidy syndrome, baker Vinters syndrome, bobble-head doll syndrome, Boerhaave syndrome, Cantu Sanchez-Corona Fragoso syndrome, Cantu Sanchez-Corona Hernandez syndrome, carbon baby syndrome, Carnevale hernandez castillo syndrome, Cartwright Nelson Fryns syndrome, Charles bonnet syndrome, Parinaud syndrome, corticobasal degeneration disorder, hair defect with photosensitivity and intellectual disability syndrome, AIDS dysmorphic syndrome, congenital acardia, acute lymphoblastic leukemia congenital sporadic aniridia, aglossia and situs inversus, agyria pachygyria polymicrogyria, agyria-pachygyria type 1, Ahumada Del Castillo syndrome, alopecia congenita keratosis palmoplantaris, alpha-mannosidosis type 1, aluminosis, Mauriac syndrome, ankle defects short stature, ankyloblepharon filiforme imperforate anus, annular constricting bands, anophthalmia cleft palate micrognathia, anophthalmia esophageal atresia cryptorchidism, anotia facial palsy cardiac defect, aortic dissection lentiginosis, childhood aortic valve stenosis, arthrogryposis IUGR thoracic dystrophy, arthrogryposis multiplex congenita CNS calcification, arthrogryposis spinal muscular atrophy, asternia, atlanto-axial fusion, atrophoderma of Pierini and Pasini, Barnicoat Baraitser syndrome, Basedow’s coma, BD syndrome, Beardwell syndrome, bhaskar jagannathan syndrome, bidirectional tachycardia, bilirubin induced brain injury in the newborn, blepharo naso facial syndrome van Maldergem type, bone dysplasia corpus callosum agenesis, brachydactyly absence of distal phalanges, brachydactyly anonychia, brachydactyly small stature face anomalies, brachydactyly tibial hypoplasia, brittle bone syndrome lethal type, bronchiectasis oligospermia, Brunsting-Perry syndrome, bruyn scheltens syndrome, burn goodship syndrome, camptodactyly joint contractures and facial skeletal dysplasia, camptodactyly vertebral fusion, Cantu Sanchez-Corona Garcia-Cruz syndrome, cardiac hydatid cysts with intracavitary expansion, cardioencephalomyopathy, cardiofacial syndrome short limbs, cardiomelic syndrome stratton Koehler type, cardiomyopathy and deafness due to tRNA lysine gene mutation, cardiomyopathy diabetes deafness, cardiomyopathy hypogonadism collagenoma syndrome, cardiomyopathy hypogonadism metabolic anomalies, cardiomyopathy spherocytosis, carpo tarsal osteolysis recessive, autosomal dominant cataract, cataract skeletal anomalies, cennamo gangemi syndrome, cerebellar agenesis, cerebello-olivary atrophy, cerebral calcification cerebellar hypoplasia, cerebral calcifications opalescent teeth phosphaturia, oculo digital syndrome, chondrodysplasia, choreoacanthocytosis amyotrophic, chorioretinopathy dominant form microcephaly, Christian Demyer Franken syndrome, Christian Johnson angenieta syndrome, chromosome 3 duplication syndrome, chronic demyelinizing neuropathy with IgM monoclonal, ciliary dyskinesia-bronchiectasis, circumscribed cutaneous aplasia of the vertex, circumscribed disseminated keratosis Jadassohn lew type, cleft lip and palate malrotation cardiopathy, cleft lip and/or palate with mucous cysts of lower, cleft lip palate dysmorphism kumar type, cleft lip palate intellectual disability corneal opacity, cleft lip palate oligodontia syndactyly pili torti, cleft lip palate pituitary deficiency, cleft lip palate-tetraphocomelia, cleft lower lip cleft lateral canthi chorioretinal, cleft palate cardiac defect ectrodactyly, cleft palate colobomata radial synostosis deafness, cleft palate heart disease polydactyly absent tibia, cleft tongue, coarse face hypotonia constipation, Cohen Lockood Wyborney syndrome, type 2 collagenopathy, Collins-Sakati syndrome, coloboma porencephaly hydronephrosis, colobomata unilobar lung heart defect, colonic malakoplakia, Colver Steer Godman syndrome, Combarros Calleja Leno syndrome, complement receptor deficiency, congenital absence of the sternocleidomastoid muscle, congenital amputation, congenital aneurysms of the great vessels, congenital articular rigidity, congenital benign spinal muscular atrophy dominant, congenital cardiovascular shunt, congenital contractures, congenital craniosynostosis maternal hyperthyroiditis, congenital cystic eye, congenital heart disease ptosis hypodontia craniostosis, congenital heart disease radio ulnar synostosis intellectual disability, congenital mumps, congenital stenosis of cervical medullary canal, Dennis-Fairhurst-Moore syndrome, congenital unilateral pulmonary hypoplasia, congenital vagal hyperreflexivity, Cormier Rustin Munnich syndrome, corneal crystals myopathy neuropathy, corneal dystrophy ichthyosis microcephaly intellectual disability, corneal dystrophy pigmentary anomaly malabsorption, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cortada Koussef Matsumoto syndrome, Cortes Lacassie syndrome, craniofacial and skeletal defects, craniofacial dysostosis arthrogryposis progeroid appearance, craniofrontonasal syndrome Teebi type, craniostenosis with congenital heart disease intellectual disability, crawfurd syndrome, cutis gyratum acanthosis nigricans craniosynostosis, cutis laxa osteoporosis, Davenport-Donlan syndrome, Davis Lafer syndrome, de Hauwere Leroy adriaenssens syndrome, deafness conductive stapedial ear malformation facial palsy, deafness goiter stippled epiphyses, deafness hypospadias metacarpal and metatarsal syndrome, deafness mesenteric diverticula of small bowel neuropathy, deafness peripheral neuropathy arterial disease, deafness progressive cataract autosomal dominant, dermatocardioskeletal syndrome boronne type, dextrocardia with situs inversus, diabetes persistent mullerian ducts, diaphragmatic agenesis radial aplasia omphalocele, diaphragmatic hernia exomphalos corpus callosum agenesis, diaphragmatic hernia upper limb defects, die Smulders droog van dijk syndrome, diomedi bernardi placidi syndrome, diphallus rachischisis imperforate anus, distichiasis heart congenital anomalies, double discordia, double uterus-hemivagina-renal agenesis, Drachtman Weinblatt Sitarz syndrome, Duker-Weiss-Siber syndrome, duodenal atresia tetralogy of fallot, duplication of leg mirror foot, duplication of the thumb unilateral biphalangeal, dupont sellier chochillon syndrome, dwarfism bluish sclerae, dwarfism deafness retinitis pigmentosa, dwarfism lethal type advanced bone age, dwarfism thin bones multiple fractures, dysmorphism cleft palate loose skin, Eagle syndrome, ectrodactyly cardiopathy dysmorphism, Elliott ludman Teebi syndrome, enamel hypoplasia cataract hydrocephaly, encephalocele anencephaly, enchondromatosis dwarfism deafness, Engelhard Yatziv syndrome, enlarged vestibular aqueduct syndrome, epidermal nevus vitamin D resistant rickets, epimetaphyseal dysplasia cataract, epiphyseal dysplasia dysmorphism camptodactyly, esophageal atresia coloboma talipes, extrasystoles short stature hyperpigmentation microcephaly, facial clefting corpus callosum agenesis, facio digito genital syndrome recessive form, facio skeletal genital syndrome rippberger type, familial capillaro-venous leptomeningeal angiomatosis, Dursun syndrome, Faye-Petersen-Ward-Carey syndrome, feigenbaum Bergeron syndrome, Feingold trainer syndrome, fetal brain disruption sequence, fetal enterovirus syndrome, fetal parainfluenza virus type 3 syndrome, fetal phenothiazine syndrome, fibromatosis multiple non ossifying, fibula aplasia complex brachydactyly, fibular hypoplasia scapulo pelvic dysplasia absent, Fitz-Hugh-Curtis syndrome, focal alopecia congenital megalencephaly, focal or multifocal malformations in neuronal migration, foix chavany Marie syndrome, Fontaine farriaux blanckaert syndrome, Fraser Jequier Chen syndrome, Freiberg disease, Friedman Goodman syndrome, frontonasal malformation cloacal exstrophy, frontonasal dysplasia Klippel feil syndrome, frontonasal dysplasia phocomelic upper limbs, Fryns Fabry Remans syndrome, Fryns Smeets Thiry syndrome, Fuchs atrophia gyrata chorioideae et retinae, Fukuda-Miyanomae-Nakata syndrome, Fuqua Berkovitz syndrome, Garret-Tripp syndrome, gas bloat syndrome, Gaucher ichthyosis restrictive dermopathy, gershinibaruch Leibo syndrome, Ghose-Sachdev-Kumar syndrome, gigantism advanced bone age hoarse cry, glossopalatine ankylosis micrognathia ear anomalies, goldstein hutt syndrome, goniodysgenesis intellectual disability short stature, green sandford davison syndrome, grix Blankenship Peterson syndrome, Ho-Kaufman-McAlister syndrome, Jaffer-Beighton syndrome, Judge Misch wright syndrome, Kashani-Strom-Utley syndrome, Kasznica-Carlson-Coppedge syndrome, Katsantoni-Papadakou-Lagoyanni syndrome, Kocher-debre-Semelaigne syndrome, Koone-Rizzo-Elias syndrome, Kozlowski Brown Hardwick syndrome, Kozlowski Ouvrier syndrome, Kozlowski Rafinski Klicharska syndrome, Kozlowski Warren Fisher syndrome, Krauss Herman Holmes syndrome, Krieble Bixler syndrome, Kuster Majewski Hammerstein syndrome, Kuster syndrome, Laugier-Hunziker syndrome, Laurence-Prosser-Rocker syndrome, le Marec-Bracq-Picaud syndrome, levator syndrome, Marinesco-Sjogren-like syndrome, Milner-Khallouf-Gibson syndrome, radio-digito-facial dysplasia, Seckel like syndrome majoor-krakauer type, neonatal aspiration syndrome, muscular fibrosis multifocal obstructed vessels, short stature contractures hypotonia, Alice in Wonderland syndrome, megacystis-microcolon-intestinal hypoperistalsis syndrome, Basilicata-Akhtar syndrome, Liberfarb syndrome, craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome, cardiac, facial, and digital anomalies with developmental delay, fibrosis, neurodegeneration, and cerebral angiomatosis, Duane anomaly-myopathy-scoliosis syndrome, congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, acute radiation syndrome, monoclonal mast cell activation syndrome, oculocerebrodental syndrome, syndromic congenital sodium diarrhea, congenital brachyesophagus-intrathoracic stomach-vertebral anomalies syndrome, intellectual disability-cardiac anomalies-short stature-joint laxity syndrome, intrauterine growth restriction-congenital multiple café-au-lait macules-increased sister chromatid exchange syndrome, frontonasal dysplasia-bifid nose-upper limb anomalies syndrome, microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome, diaphragmatic hernia-short bowel-asplenia syndrome, warts-immunodeficiency-lymphedema-anogenital dysplasia syndrome, Cramp-fasciculation syndrome, choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome, blepharophimosis-intellectual disability syndrome/genitopatellar overlap syndrome, CCNK-related neurodevelopmental disorder-severe intellectual disability-facial dysmorphism syndrome, cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome, KLHL7-related Bohring-Opitz-like syndrome, KLHL7-related cold-induced sweating-like syndrome, KAT6B-related multiple congenital anomalies syndrome, oculogastrointestinal-neurodevelopmental syndrome, spastic paraparesis-cataracts-speech delay syndrome, Ruzicka-Goerz-Anton syndrome, Sammartino-Decreccio syndrome, Samson-Gardner syndrome, Samson-Viljoen syndrome, Sanderson-Fraser syndrome, Sandhaus-Ben-Ami syndrome, prostatic malacoplakia associated with prostatic abscess, Saul-Wilkes-Stevenson syndrome, macrogyria, pseudobulbar palsy and intellectual disability, Schwartz-Cohen-addad-Lambert syndrome, Schlegelberger-Grote syndrome, Schrander-stumpel-Theunissen-Hulsmans syndrome, Saal-Bulas syndrome, Sackey-Sakati-Aur syndrome, Slti-Salem syndrome, Zerres Rietschel Majewski syndrome, Zazam Sheriff Phillips syndrome, Zadik-Barak-Levin syndrome, weinstein kliman scully syndrome, thickened earlobes with conductive deafness from incus-stapes abnormalities, ichthyosis linearis circumflexa, infantile striato thalamic degeneration, Landy-Donnai syndrome, merlob grunebaum reisner syndrome, Pavone Fiumara Rizzo syndrome, pfeiffer rockelein syndrome, Pfeiffer Tietze Welte syndrome, phosphoribosylpyrophosphate synthetase deficiency, piepkorn karp hickok syndrome, podder-tolmie syndrome, pointer syndrome, richieri-costa guion-almeida cohen syndrome, Rubinstein Taybi like syndrome, ruvalcaba churesigaew myhre syndrome, short limb dwarf lethal colavita kozlowski type, Mallory-Weiss syndrome, superior vena cava syndrome, piriformis syndrome, engraftment syndrome, Adams-Stokes syndrome, Leriche syndrome, multiple organ dysfunction syndrome, posterior leukoencephalopathy syndrome, cardio-renal syndrome, Rahman syndrome, X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome, retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, Lopes-Maciel-Rodan syndrome, Stankiewicz-Isidor syndrome, Skraban-Deardorff syndrome, joint laxity, short stature, and myopia, Sweeney-Cox syndrome, Alkuraya-Kucinskas syndrome, Jaberi-Elahi syndrome, neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, hearing impairment and infertile male syndrome, cardiocutaneous syndrome, neonatal diabetes, congenital sensorineural hearing loss and congenital cataracts, cardioectodermal syndrome, cannabinoid hyperemesis syndrome, retrograde cricopharyngeus dysfunction, Zinner syndrome, retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome, IFAP syndrome, DICER1-related tumor predisposition, Roberts-SC phocomelia syndrome, carcinoid syndrome, Bonnevie-Ullrich syndrome, NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, RNU4ATAC spectrum disorder, syndromic congenital heart disease, hand-foot syndrome, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, gastrointestinal defects and immunodeficiency syndrome 1, achalasia-alacrima syndrome, black locks with albinism and deafness syndrome, Birt-Hogg-Dube syndrome, trigeminal trophic syndrome, developmental and/or epileptic encephalopathy with spike-wave activation in sleep, syndromic microspherophakia, painful legs and moving toes syndrome, congenital aphakia-iris hypoplasia-microphthalmia-microcornea syndrome, hereditary persistence of fetal hemoglobin-intellectual disability syndrome, developmental delay-immunodeficiency-leukoencephalopathy-hypohomocysteinemia syndrome, primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome, post-cardiac arrest syndrome, early-onset obesity-hyperphagia-severe developmental delay syndrome, hereditary alpha tryptasemia syndrome, KINSSHIP syndrome, developmental delay, hypotrophy, and dysmorphic features without moebius syndrome, breast implant illness, cataracts, hearing impairment, nephrotic syndrome, and enterocolitis, craniosynostosis-facial dysmorphism-chiari-1 malformation-developmental and language delay syndrome, MYT1L-related developmental delay-intellectual disability-obesity syndrome, Houge-Janssens syndrome, xerosis and growth failure with immune and pulmonary dysfunction syndrome, Fliedner-Zweier syndrome, Lui-Jee-Baron syndrome, Long-Olsen-Distelmaier syndrome, Tan-Almurshedi syndrome, diabetes, deafness, developmental delay, and short stature syndrome, Alfadhel syndrome, Hoxha-Aliu syndrome, cleft palate-congenital heart defect-intellectual disability syndrome, congenital insensitivity to pain syndrome, Marsili type, Yuksel-Vogel-Bauer syndrome, polydactyly-macrocephaly syndrome, pyoderma gangrenosum-acne-hidradenitis suppurativa-ankylosing spondylitis syndrome, psoriatic arthritis-pyoderma gangrenosum-acne-hidradenitis suppurativa syndrome, megalencephaly-polydactyly syndrome, Leigh syndrome, mitochondrial, auroneurodental syndrome, orofacial clefting-cardiac anomalies-facial dysmorphism syndrome, Grisel syndrome, arterial tortuosity-bone fragility syndrome, dialysis disequilibrium syndrome, brain abnormalities-severe developmental delay-facial dysmorphism-intellectual disability syndrome due to MEF2C mutation, Kariminejad neurodevelopmental syndrome, myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities, brain malformation renal syndrome, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2, Karayol-Borroto-Haghshenas neurodevelopmental syndrome, neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, Morimoto-Ryu-Malicdan neuromuscular syndrome, neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, neurodevelopmental disorder with variable familial hypercholanemia, Pan-Chung-Bellen syndrome, telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature, Muggenthaler-Chowdhury-Chioza syndrome, Tayoun-Maawali syndrome, ragopathy, cardiovascular-kidney-metabolic syndrome, craniofaciocardiohepatic syndrome, FICUS syndrome, Li-Takada-Miyake syndrome, Guillouet-Gordon syndrome, ICHAD syndrome, cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome, RAC2-related combined immunodeficiency-bronchiectasis-cancer-predisposing syndrome, oculovertebral syndrome, Alsahan-Harris syndrome, Ververi-Brady syndrome, Dursun-Ozgul neurodevelopmental syndrome, immune dysregulation, neurodevelopmental defects, and colitis, Harel-Tora neurodevelopmental syndrome, Valence-Farazi cerebellar ataxia syndrome, dyschromatosis, ichthyosis, deafness, and atopic disease, Ramond-Elliott neurodevelopmental syndrome, STAD syndrome, craniosynostosis-scoliosis syndrome, loin pain hematuria syndrome, IRF6-related condition, linkeropathy, NDUFB11-related disorders, CRYAB-related myofibrillar myopathy-cataract-cardiomyopathy spectrum disorder, TSEN2-related neurodevelopmental disorder with or without thrombotic microangiopathy, antiphospholipid syndrome

Subtypes (8): developmental and epileptic encephalopathy, 2, developmental and epileptic encephalopathy, 1, developmental and epileptic encephalopathy, 5, developmental and epileptic encephalopathy, 12, developmental and epileptic encephalopathy, 15, developmental and epileptic encephalopathy, 27, developmental and epileptic encephalopathy, 30, developmental and epileptic encephalopathy, 40

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

46 retrieved; paginated sample, class counts are floors:

22 pathogenic, 12 pathogenic/likely pathogenic, 4 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 uncertain significance, 2 not provided, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
156097	NM_001323289.2(CDKL5):c.99+1G>T	CDKL5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2687750	NM_001323289.2(CDKL5):c.404-1G>C	CDKL5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
94113	NM_001323289.2(CDKL5):c.533G>A (p.Arg178Gln)	CDKL5	Pathogenic	reviewed by expert panel
1705841	NM_004408.4(DNM1):c.590-2A>G	DNM1	Pathogenic	criteria provided, single submitter
167208	NM_172107.4(KCNQ2):c.821C>T (p.Thr274Met)	KCNQ2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11186	NM_139058.3(ARX):c.306GGC[17] (p.Ala109_Ala115dup)	LOC109610631	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1707404	GRCh38/hg38 2q24.3(chr2:165383106-167432622)x1	LOC126806397	Pathogenic	criteria provided, single submitter
3062161	GRCh38/hg38 16q23.1(chr16:78064581-78164300)x1	LOC132090427	Pathogenic	criteria provided, single submitter
1342670	NM_001040142.2(SCN2A):c.1261T>G (p.Leu421Val)	SCN2A	Pathogenic	no assertion criteria provided
1342671	NM_001040142.2(SCN2A):c.4364T>A (p.Ile1455Asn)	SCN2A	Pathogenic	no assertion criteria provided
1342673	NM_001040142.2(SCN2A):c.5144G>T (p.Gly1715Val)	SCN2A	Pathogenic	no assertion criteria provided
1342674	NM_001040142.2(SCN2A):c.4498G>A (p.Ala1500Thr)	SCN2A	Pathogenic	criteria provided, single submitter
1342675	NM_001040142.2(SCN2A):c.5198del (p.Pro1733fs)	SCN2A	Pathogenic	no assertion criteria provided
1342679	NM_001040142.2(SCN2A):c.4015A>G (p.Asn1339Asp)	SCN2A	Pathogenic	no assertion criteria provided
1342680	NM_001040142.2(SCN2A):c.5558A>G (p.His1853Arg)	SCN2A	Pathogenic	no assertion criteria provided
1342682	NM_001040142.2(SCN2A):c.4712T>C (p.Ile1571Thr)	SCN2A	Pathogenic	criteria provided, single submitter
1342683	NM_001040142.2(SCN2A):c.4523A>T (p.Lys1508Ile)	SCN2A	Pathogenic	no assertion criteria provided
1342684	NM_001040142.2(SCN2A):c.807G>T (p.Leu269Phe)	SCN2A	Pathogenic	no assertion criteria provided
1342685	NM_001040142.2(SCN2A):c.4948C>A (p.Leu1650Ile)	SCN2A	Pathogenic	no assertion criteria provided
1342689	NM_001040142.2(SCN2A):c.5640A>C (p.Glu1880Asp)	SCN2A	Pathogenic	no assertion criteria provided
1342694	NM_001040142.2(SCN2A):c.1288G>A (p.Glu430Lys)	SCN2A	Pathogenic	no assertion criteria provided
1342695	NM_001040142.2(SCN2A):c.707C>G (p.Thr236Ser)	SCN2A	Pathogenic	no assertion criteria provided
194555	NM_001040142.2(SCN2A):c.2558G>A (p.Arg853Gln)	SCN2A	Pathogenic	reviewed by expert panel
196039	NM_001040142.2(SCN2A):c.5645G>A (p.Arg1882Gln)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
206981	NM_001040142.2(SCN2A):c.2995G>A (p.Glu999Lys)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
206996	NM_001040142.2(SCN2A):c.4025T>C (p.Leu1342Pro)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
206997	NM_001040142.2(SCN2A):c.4036A>G (p.Ile1346Val)	SCN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
207024	NM_001040142.2(SCN2A):c.5317G>A (p.Ala1773Thr)	SCN2A	Pathogenic	reviewed by expert panel
29886	NM_001040142.2(SCN2A):c.3631G>A (p.Glu1211Lys)	SCN2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
135651	NM_001330260.2(SCN8A):c.2549G>A (p.Arg850Gln)	SCN8A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 135 · Orphanet: 65 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SCN2A	Strong	Autosomal dominant	seizures, benign familial infantile, 3	16
ARX	Supportive	Autosomal dominant	infantile spasms	16
CDKL5	Supportive	Autosomal dominant	infantile spasms	9
CNPY3	Supportive	Autosomal dominant	infantile spasms	4
GRIN2B	Supportive	Autosomal dominant	infantile spasms	9
GUF1	Supportive	Autosomal dominant	infantile spasms	3
NTRK2	Supportive	Autosomal dominant	infantile spasms	8
PHACTR1	Supportive	Autosomal dominant	infantile spasms	5
PIGA	Supportive	Autosomal dominant	infantile spasms	9
PLCB1	Supportive	Autosomal dominant	infantile spasms	6
SIK1	Supportive	Autosomal dominant	infantile spasms	7
SPTAN1	Supportive	Autosomal dominant	infantile spasms	10
ST3GAL3	Supportive	Autosomal dominant	infantile spasms	7
STXBP1	Supportive	Autosomal dominant	infantile spasms	12
WDR45	Supportive	Autosomal dominant	infantile spasms	8
BRWD3	Limited	Autosomal dominant	infantile spasms	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN2A	Orphanet:140927	Self-limited neonatal-infantile epilepsy
SCN2A	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
SCN2A	Orphanet:2131	Alternating hemiplegia of childhood
SCN2A	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
SCN2A	Orphanet:306	Self-limited infantile epilepsy
SCN2A	Orphanet:33069	Dravet syndrome
SCN2A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN2A	Orphanet:697160	Infantile epileptic spasms syndrome
CDKL5	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
CDKL5	Orphanet:3095	Atypical Rett syndrome
CDKL5	Orphanet:505652	CDKL5-deficiency disorder
CDKL5	Orphanet:697160	Infantile epileptic spasms syndrome
STXBP1	Orphanet:495818	9q33.3q34.11 microdeletion syndrome
STXBP1	Orphanet:599373	STXBP1-related encephalopathy
GRIN2B	Orphanet:589547	GRIN2B-related developmental delay, intellectual disability and autism spectrum disorder
GRIN2B	Orphanet:697160	Infantile epileptic spasms syndrome
ST3GAL3	Orphanet:697734	ST3GAL3-CDG
SIK1	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
SIK1	Orphanet:697160	Infantile epileptic spasms syndrome
SPTAN1	Orphanet:697160	Infantile epileptic spasms syndrome
CNPY3	Orphanet:697160	Infantile epileptic spasms syndrome
PLCB1	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
PLCB1	Orphanet:697160	Infantile epileptic spasms syndrome
BRWD3	Orphanet:528084	Non-specific syndromic intellectual disability
ARX	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
ARX	Orphanet:2508	Corpus callosum agenesis-abnormal genitalia syndrome
ARX	Orphanet:3175	X-linked spasticity-intellectual disability-epilepsy syndrome
ARX	Orphanet:364063	Infantile epileptic-dyskinetic encephalopathy
ARX	Orphanet:452	X-linked lissencephaly with abnormal genitalia
ARX	Orphanet:697160	Infantile epileptic spasms syndrome
ARX	Orphanet:777	X-linked non-syndromic intellectual disability
ARX	Orphanet:94083	Partington syndrome
PHACTR1	Orphanet:697160	Infantile epileptic spasms syndrome
GUF1	Orphanet:697160	Infantile epileptic spasms syndrome
WDR45	Orphanet:329284	Beta-propeller protein-associated neurodegeneration
WDR45	Orphanet:697160	Infantile epileptic spasms syndrome
NTRK2	Orphanet:251615	Pilomyxoid astrocytoma
NTRK2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
NTRK2	Orphanet:697160	Infantile epileptic spasms syndrome
NTRK2	Orphanet:99704	Early-onset obesity-hyperphagia-severe developmental delay syndrome
PIGA	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
PIGA	Orphanet:300496	Multiple congenital anomalies-hypotonia-seizures syndrome type 2
PIGA	Orphanet:397922	Ferro-cerebro-cutaneous syndrome
PIGA	Orphanet:447	Paroxysmal nocturnal hemoglobinuria
PIGA	Orphanet:697160	Infantile epileptic spasms syndrome
SCN8A	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
SCN8A	Orphanet:306	Self-limited infantile epilepsy
SCN8A	Orphanet:352582	Familial infantile myoclonic epilepsy
SCN8A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
WWOX	Orphanet:251510	46,XY partial gonadal dysgenesis

Cohort genes → proteins

22 cohort genes, 22 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	22

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN2A	HGNC:10588	ENSG00000136531	Q99250	Sodium channel protein type 2 subunit alpha	gencc,clinvar
CDKL5	HGNC:11411	ENSG00000008086	O76039	Cyclin-dependent kinase-like 5	gencc,clinvar
STXBP1	HGNC:11444	ENSG00000136854	P61764	Syntaxin-binding protein 1	gencc,clinvar
GRIN2B	HGNC:4586	ENSG00000273079	Q13224	Glutamate receptor ionotropic, NMDA 2B	gencc,clinvar
ST3GAL3	HGNC:10866	ENSG00000126091	Q11203	CMP-N-acetylneuraminate-beta-1,4-galactoside alpha-2,3-sialyltransferase	gencc
SIK1	HGNC:11142	ENSG00000142178	P57059	Serine/threonine-protein kinase SIK1	gencc
SPTAN1	HGNC:11273	ENSG00000197694	Q13813	Spectrin alpha chain, non-erythrocytic 1	gencc
CNPY3	HGNC:11968	ENSG00000137161	Q9BT09	Protein canopy homolog 3	gencc
PLCB1	HGNC:15917	ENSG00000182621	Q9NQ66	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1	gencc
BRWD3	HGNC:17342	ENSG00000165288	Q6RI45	Bromodomain and WD repeat-containing protein 3	gencc
ARX	HGNC:18060	ENSG00000004848	Q96QS3	Homeobox protein ARX	gencc
PHACTR1	HGNC:20990	ENSG00000112137	Q9C0D0	Phosphatase and actin regulator 1	gencc
GUF1	HGNC:25799	ENSG00000151806	Q8N442	Translation factor GUF1, mitochondrial	gencc
WDR45	HGNC:28912	ENSG00000196998	Q9Y484	WD repeat domain phosphoinositide-interacting protein 4	gencc
NTRK2	HGNC:8032	ENSG00000148053	Q16620	BDNF/NT-3 growth factors receptor	gencc
PIGA	HGNC:8957	ENSG00000165195	P37287	Phosphatidylinositol N-acetylglucosaminyltransferase subunit A	gencc
SCN8A	HGNC:10596	ENSG00000196876	Q9UQD0	Sodium channel protein type 8 subunit alpha	clinvar
UGDH	HGNC:12525	ENSG00000109814	O60701	UDP-glucose 6-dehydrogenase	clinvar
WWOX	HGNC:12799	ENSG00000186153	Q9NZC7	WW domain-containing oxidoreductase	clinvar
TUBA1A	HGNC:20766	ENSG00000167552	Q71U36	Tubulin alpha-1A chain	clinvar
DNM1	HGNC:2972	ENSG00000106976	Q05193	Dynamin-1	clinvar
KCNQ2	HGNC:6296	ENSG00000075043	O43526	Potassium voltage-gated channel subfamily KQT member 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN2A	Sodium channel protein type 2 subunit alpha	Mediates the voltage-dependent sodium ion permeability of excitable membranes.
CDKL5	Cyclin-dependent kinase-like 5	Mediates phosphorylation of MECP2.
STXBP1	Syntaxin-binding protein 1	Participates in the regulation of synaptic vesicle docking and fusion through interaction with GTP-binding proteins.
GRIN2B	Glutamate receptor ionotropic, NMDA 2B	Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+).
ST3GAL3	CMP-N-acetylneuraminate-beta-1,4-galactoside alpha-2,3-sialyltransferase	Catalyzes the formation of the NeuAc-alpha-2,3-Gal-beta-1,4-GlcNAc-, NeuAc-alpha-2,3-Gal-beta-1,3-GlcNAc- and NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc- sequences found in terminal carbohydrate groups of glycoproteins and glycolipids.
SIK1	Serine/threonine-protein kinase SIK1	Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression.
SPTAN1	Spectrin alpha chain, non-erythrocytic 1	Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.
CNPY3	Protein canopy homolog 3	Toll-like receptor (TLR)-specific co-chaperone for HSP90B1.
PLCB1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1	Catalyzes the hydrolysis of 1-phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) and mediates intracellular signaling downstream of G protein-coupled receptors.
BRWD3	Bromodomain and WD repeat-containing protein 3	Plays a role in the regulation of cell morphology and cytoskeletal organization.
ARX	Homeobox protein ARX	Transcription factor.
PHACTR1	Phosphatase and actin regulator 1	Binds actin monomers (G actin) and plays a role in multiple processes including the regulation of actin cytoskeleton dynamics, actin stress fibers formation, cell motility and survival, formation of tubules by endothelial cells, and regula…
GUF1	Translation factor GUF1, mitochondrial	Promotes mitochondrial protein synthesis.
WDR45	WD repeat domain phosphoinositide-interacting protein 4	Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation.
NTRK2	BDNF/NT-3 growth factors receptor	Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticit…
PIGA	Phosphatidylinositol N-acetylglucosaminyltransferase subunit A	Catalytic subunit of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first s…
SCN8A	Sodium channel protein type 8 subunit alpha	Pore-forming subunit of a voltage-gated sodium channel complex assuming opened or closed conformations in response to the voltage difference across membranes and through which sodium ions selectively pass along their electrochemical gradie…
UGDH	UDP-glucose 6-dehydrogenase	Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans.
WWOX	WW domain-containing oxidoreductase	Putative oxidoreductase.
TUBA1A	Tubulin alpha-1A chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
DNM1	Dynamin-1	Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission and participates in many forms of endocytosis, such as clathrin-mediated endocytosis or synaptic vesicle endocytosis as well as rapid endocytosis (RE).
KCNQ2	Potassium voltage-gated channel subfamily KQT member 2	Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability.

Protein-family classification

Druggable: 9 · Difficult: 6 · Unknown: 7 · Druggable fraction: 0.41

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	3	15.2×	0.006
Scaffold/PPI	5	3.9×	0.022
Kinase	3	3.8×	0.086
Enzyme (other)	3	1.6×	0.415
Other/Unknown	7	0.6×	0.994
Transcription factor	1	0.4×	0.994

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN2A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
CDKL5	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
STXBP1	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
GRIN2B	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt
ST3GAL3	Enzyme (other)	yes	2.4.99.2	Glyco_trans_29, Sialyl_trans, GT29-like_sf
SIK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
SPTAN1	Scaffold/PPI	no		SH3_domain, Spectrin_repeat, EF_hand_dom
CNPY3	Other/Unknown	no		DUF3456
PLCB1	Enzyme (other)	yes	3.1.4.11	C2_dom, PLipase_C_PInositol-sp_X_dom, PI-PLC_fam
BRWD3	Scaffold/PPI	no		Bromodomain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
ARX	Transcription factor	no		HD, OAR_dom, Homeodomain-like_sf
PHACTR1	Other/Unknown	no		RPEL_repeat
GUF1	Other/Unknown	no		EFG_V-like, T_Tr_GTP-bd_dom, EFTu-like_2
WDR45	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
NTRK2	Kinase	yes	2.7.10.1	LRRNT, Cys-rich_flank_reg_C, Prot_kinase_dom
PIGA	Other/Unknown	no		Glyco_trans_1, PIGA_GPI_anchor_biosynthesis, PIG-A/GPI3
SCN8A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
UGDH	Enzyme (other)	yes	1.1.1.22	UDP-Glc/GDP-Man_DH_N, 6-PGluconate_DH-like_C_sf, UDP-Glc/GDP-Man_DH_dimer
WWOX	Scaffold/PPI	no		WW_dom, SDR_fam, WW_dom_sf
TUBA1A	Other/Unknown	no		Tubulin, Alpha_tubulin, Tubulin_FtsZ_GTPase
DNM1	Scaffold/PPI	no	3.6.5.5	Dynamin_stalk, Dynamin_GTPase, PH_domain
KCNQ2	Ion channel	yes		K_chnl_volt-dep_KCNQ, K_chnl_volt-dep_KCNQ2, Ion_trans_dom

Expression context

Cohort genes with no expression data: 0.

22 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	22
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	6
cortical plate	4
middle temporal gyrus	3
mucosa of stomach	3
cerebellar cortex	3
cerebellar hemisphere	3
right hemisphere of cerebellum	3
gastrocnemius	2
muscle of leg	2
granulocyte	2
endothelial cell	2
postcentral gyrus	2
cranial nerve II	2
cerebellar vermis	1
frontal pole	1
lateral nuclear group of thalamus	1
buccal mucosa cell	1
hindlimb stylopod muscle	1
skin of abdomen	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN2A	187	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, cerebellar vermis
CDKL5	257	ubiquitous	marker	frontal pole, Brodmann (1909) area 23, cortical plate
STXBP1	287	ubiquitous	marker	middle temporal gyrus, lateral nuclear group of thalamus, Brodmann (1909) area 23
GRIN2B	138	broad	marker	buccal mucosa cell, cortical plate, Brodmann (1909) area 23
ST3GAL3	178	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, muscle of leg
SIK1	138	not_expressed	marker	mucosa of stomach, skin of abdomen, zone of skin
SPTAN1	293	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
CNPY3	283	ubiquitous	marker	monocyte, granulocyte, leukocyte
PLCB1	278	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, superior frontal gyrus
BRWD3	223	ubiquitous	marker	tendon of biceps brachii, epithelial cell of pancreas, calcaneal tendon
ARX	162	broad	marker	left ovary, ovary, right ovary
PHACTR1	210	ubiquitous	marker	cortical plate, postcentral gyrus, nucleus accumbens
GUF1	268	ubiquitous	marker	ventricular zone, gastrocnemius, muscle of leg
WDR45	293	ubiquitous	marker	apex of heart, mucosa of stomach, granulocyte
NTRK2	273	broad	marker	cranial nerve II, lateral globus pallidus, CA1 field of hippocampus
PIGA	266	ubiquitous	marker	secondary oocyte, mucosa of stomach, endometrium epithelium
SCN8A	194	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, postcentral gyrus
UGDH	278	ubiquitous	marker	colonic mucosa, mucosa of sigmoid colon, islet of Langerhans
WWOX	286	ubiquitous	marker	parotid gland, cervix squamous epithelium, cranial nerve II
TUBA1A	288	ubiquitous	marker	endothelial cell, cortical plate, ganglionic eminence
DNM1	257	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
KCNQ2	183	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 14.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WWOX	5,892
NTRK2	5,190
DNM1	3,614
GRIN2B	3,611
KCNQ2	3,388
GUF1	3,147
SPTAN1	3,083
STXBP1	3,003
SCN2A	2,810
BRWD3	2,714

Intra-cohort edges

A	B	Sources
ARX	CDKL5	string_interaction
ARX	PLCB1	string_interaction
ARX	SPTAN1	string_interaction
ARX	STXBP1	string_interaction
CDKL5	KCNQ2	string_interaction
CDKL5	SCN2A	string_interaction
CDKL5	STXBP1	string_interaction
KCNQ2	SCN2A	string_interaction
KCNQ2	SCN8A	string_interaction
KCNQ2	STXBP1	string_interaction
KCNQ2	TUBA1A	biogrid_interaction
NTRK2	SCN2A	biogrid_interaction, intact
SCN2A	STXBP1	string_interaction
SPTAN1	STXBP1	string_interaction

Structural data

PDB: 14 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNQ2	O43526	39
GRIN2B	Q13224	36
DNM1	Q05193	22
UGDH	O60701	20
TUBA1A	Q71U36	15
NTRK2	Q16620	9
SPTAN1	Q13813	7
SCN8A	Q9UQD0	7
PHACTR1	Q9C0D0	6
SCN2A	Q99250	5
CDKL5	O76039	3
WDR45	Q9Y484	3
STXBP1	P61764	1
WWOX	Q9NZC7	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ST3GAL3	Q11203	90.87
PIGA	P37287	86.22
PLCB1	Q9NQ66	84.55
GUF1	Q8N442	81.89
CNPY3	Q9BT09	73.76
BRWD3	Q6RI45	65.11
SIK1	P57059	61.31
ARX	Q96QS3	56.51

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 207. Enrichment computed across 22 evidence-associated genes (17 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 17 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interaction between L1 and Ankyrins	4	86.7×	2e-05	SCN2A, SCN8A, SPTAN1, KCNQ2
L1CAM interactions	5	35.4×	2e-05	SCN2A, SCN8A, SPTAN1, TUBA1A, KCNQ2
Activated NTRK2 signals through FYN	2	223.9×	0.001	GRIN2B, NTRK2
Axon guidance	5	13.3×	0.001	SCN2A, SCN8A, SPTAN1, TUBA1A, KCNQ2
Nervous system development	5	12.6×	0.001	SCN2A, SCN8A, SPTAN1, TUBA1A, KCNQ2
Phase 0 - rapid depolarisation	2	40.7×	0.037	SCN2A, SCN8A
BDNF activates NTRK2 (TRKB) signaling	1	335.9×	0.051	NTRK2
NTF3 activates NTRK2 (TRKB) signaling	1	335.9×	0.051	NTRK2
NTF4 activates NTRK2 (TRKB) signaling	1	335.9×	0.051	NTRK2
Assembly and cell surface presentation of NMDA receptors	2	29.9×	0.051	GRIN2B, TUBA1A
Recycling pathway of L1	2	26.3×	0.051	TUBA1A, DNM1
Asparagine N-linked glycosylation	3	10.6×	0.051	ST3GAL3, SPTAN1, TUBA1A
Neurexins and neuroligins	2	23.2×	0.052	STXBP1, GRIN2B
Developmental Biology	5	4.2×	0.071	SCN2A, SCN8A, SPTAN1, TUBA1A, KCNQ2
Activated NTRK2 signals through PLCG1	1	167.9×	0.079	NTRK2
Neuronal System	3	7.8×	0.079	STXBP1, TUBA1A, KCNQ2
Formation of the active cofactor, UDP-glucuronate	1	134.3×	0.081	UGDH
NGF-independant TRKA activation	1	134.3×	0.081	NTRK2
ER to Golgi Anterograde Transport	2	15.6×	0.081	SPTAN1, TUBA1A
NTRK2 activates RAC1	1	112.0×	0.086	NTRK2
Activated NTRK2 signals through CDK5	1	112.0×	0.086	NTRK2
Activated NTRK2 signals through PI3K	1	96.0×	0.086	NTRK2
Macroautophagy	2	13.6×	0.086	TUBA1A, WDR45
COPI-mediated anterograde transport	2	12.9×	0.086	SPTAN1, TUBA1A
Cardiac conduction	2	12.8×	0.086	SCN2A, SCN8A
Defective ST3GAL3 causes MCT12 and EIEE15	1	84.0×	0.087	ST3GAL3
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	1	84.0×	0.087	PLCB1
Maturation of protein 3a	1	74.6×	0.087	ST3GAL3
Acetylcholine regulates insulin secretion	1	67.2×	0.087	PLCB1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 22 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cerebral cortex development	4	37.4×	9e-04	PLCB1, TUBA1A, PHACTR1, NTRK2
glutamate receptor signaling pathway	2	85.1×	0.015	GRIN2B, PLCB1
neuron apoptotic process	3	25.2×	0.015	SCN2A, STXBP1, TUBA1A
memory	3	25.0×	0.015	SCN2A, PLCB1, TUBA1A
cardiac muscle cell action potential involved in contraction	2	63.8×	0.022	SCN2A, SCN8A
neuron migration	3	18.2×	0.023	CDKL5, TUBA1A, NTRK2
clathrin coat assembly involved in endocytosis	1	766.0×	0.029	DNM1
obsolete positive regulation of vesicle docking	1	766.0×	0.029	STXBP1
cellular response to glyceraldehyde	1	766.0×	0.029	PLCB1
regulation of acrosomal vesicle exocytosis	1	766.0×	0.029	STXBP1
negative regulation of monocyte extravasation	1	766.0×	0.029	PLCB1
UDP-glucuronate biosynthetic process	1	383.0×	0.031	UGDH
intrinsic apoptotic signaling pathway in response to osmotic stress	1	383.0×	0.031	SCN2A
embryonic olfactory bulb interneuron precursor migration	1	383.0×	0.031	ARX
phosphatidylinositol catabolic process	1	383.0×	0.031	PLCB1
activation of meiosis involved in egg activation	1	383.0×	0.031	PLCB1
vesicle scission	1	383.0×	0.031	DNM1
cellular response to fluoride	1	383.0×	0.031	PLCB1
positive regulation of glutamate secretion, neurotransmission	1	383.0×	0.031	STXBP1
action potential	2	32.6×	0.031	SCN8A, KCNQ2
learning	2	25.5×	0.031	PLCB1, NTRK2
long-term synaptic potentiation	2	25.5×	0.031	GRIN2B, NTRK2
sodium ion transport	2	24.7×	0.031	SCN2A, SCN8A
neuron development	2	23.2×	0.034	UGDH, ARX
myelination	2	22.9×	0.034	SCN2A, SCN8A
axon target recognition	1	255.3×	0.034	STXBP1
regulation of retrograde trans-synaptic signaling by endocanabinoid	1	255.3×	0.034	PLCB1
trans-synaptic signaling by BDNF, modulating synaptic transmission	1	255.3×	0.034	NTRK2
negative regulation of triglyceride biosynthetic process	1	191.5×	0.034	SIK1
cerebral cortex tangential migration	1	191.5×	0.034	ARX

Therapeutics

Drug target analysis

Approved (phase 4): 9 · Phase ≥3: 9 · Phased (≥1): 10 · Undrugged: 12

Druggability breadth: 16 of 22 evidence-associated genes (73%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SCN2A	BEPRIDIL
CDKL5	FEDRATINIB
GRIN2B	HALOPERIDOL
SIK1	FEDRATINIB
NTRK2	FEDRATINIB
SCN8A	IMIPRAMINE
TUBA1A	COLCHICINE
DNM1	CETRIMIDE
KCNQ2	FLUPIRTINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN2A	99	4
NTRK2	50	4
GRIN2B	35	4
SCN8A	25	4
TUBA1A	22	4
SIK1	19	4
CDKL5	14	4
DNM1	4	4
KCNQ2	4	4
SPTAN1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	SCN2A
DIBUCAINE	4	SCN2A
ARTICAINE	4	SCN2A
BUPIVACAINE	4	SCN2A
IMIPRAMINE	4	SCN2A, SCN8A
DROPERIDOL	4	SCN2A
DICYCLOMINE	4	SCN2A
TETRABENAZINE	4	SCN2A
PHENIRAMINE	4	SCN2A
PRILOCAINE	4	SCN2A
PROPOXYCAINE	4	SCN2A
PROPARACAINE	4	SCN2A
HEXYLCAINE	4	SCN2A
PRAMOXINE	4	SCN2A
BENOXINATE	4	SCN2A
QUINIDINE	4	SCN2A
FELODIPINE	4	SCN2A
PHENYTOIN	4	SCN2A
QUININE	4	SCN2A
NISOLDIPINE	4	SCN2A
NIFEDIPINE	4	SCN2A, SCN8A
PRAZOSIN	4	SCN2A
DILTIAZEM	4	SCN2A, SCN8A
PRENYLAMINE	4	SCN2A
COCAINE	4	SCN2A
TRIFLUOPERAZINE	4	SCN2A
CINNARIZINE	4	SCN2A
THIORIDAZINE	4	SCN2A
ETIDOCAINE	4	SCN2A
CHLORPHENIRAMINE	4	SCN2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TUBA1A	1,696	Binding:1655, Functional:35, ADMET:6
NTRK2	554	Binding:547, ADMET:5, Functional:2
GRIN2B	471	Binding:429, Functional:36, ADMET:5, Toxicity:1
SIK1	210	Binding:205, Toxicity:4, ADMET:1
SCN2A	203	Binding:172, Functional:20, ADMET:10, Toxicity:1
SCN8A	173	Binding:148, Functional:16, ADMET:7, Toxicity:2
KCNQ2	145	Binding:136, Functional:7, ADMET:1, Toxicity:1
CDKL5	74	Binding:74
PLCB1	11	Binding:9, Functional:2
DNM1	11	Binding:11
SPTAN1	7	Binding:7
BRWD3	5	Binding:5
ST3GAL3	2	Binding:2
STXBP1	1	Binding:1
CNPY3	1	Binding:1
UGDH	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CDKL5	2.7.11.22	cyclin-dependent kinase
ST3GAL3	2.4.99.2, 2.4.99.6	beta-D-galactosyl-(1->3)-N-acetyl-beta-D-galactosaminide alpha-2,3-sialyltransferase, N-acetyllactosaminide alpha-2,3-sialyltransferase
PLCB1	3.1.4.11	phosphoinositide phospholipase C
NTRK2	2.7.10.1	receptor protein-tyrosine kinase
UGDH	1.1.1.22	UDP-glucose 6-dehydrogenase
DNM1	3.6.5.5	dynamin GTPase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SCN2A	203
GRIN2B	471
SIK1	210
NTRK2	554
SCN8A	173
TUBA1A	1,696
KCNQ2	145

Pharmacogenomics

Cohort genes with a PharmGKB record: 22; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
BEPRIDIL	4	SCN2A
DIBUCAINE	4	SCN2A
ARTICAINE	4	SCN2A
BUPIVACAINE	4	SCN2A
IMIPRAMINE	4	SCN2A, SCN8A
DROPERIDOL	4	SCN2A
DICYCLOMINE	4	SCN2A
TETRABENAZINE	4	SCN2A
PHENIRAMINE	4	SCN2A
PRILOCAINE	4	SCN2A
PROPOXYCAINE	4	SCN2A
PROPARACAINE	4	SCN2A
HEXYLCAINE	4	SCN2A
PRAMOXINE	4	SCN2A
BENOXINATE	4	SCN2A
QUINIDINE	4	SCN2A
FELODIPINE	4	SCN2A
PHENYTOIN	4	SCN2A
QUININE	4	SCN2A
NISOLDIPINE	4	SCN2A
NIFEDIPINE	4	SCN2A, SCN8A
PRAZOSIN	4	SCN2A
DILTIAZEM	4	SCN2A, SCN8A
PRENYLAMINE	4	SCN2A
COCAINE	4	SCN2A
TRIFLUOPERAZINE	4	SCN2A
CINNARIZINE	4	SCN2A
THIORIDAZINE	4	SCN2A
ETIDOCAINE	4	SCN2A
CHLORPHENIRAMINE	4	SCN2A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	9	SCN2A, CDKL5, GRIN2B, SIK1, NTRK2, SCN8A, TUBA1A, DNM1, KCNQ2
B	Phased (≥1) drug, not yet approved	1	SPTAN1
C	Druggable family + PDB, no drug	1	UGDH
D	Druggable family + AlphaFold only, no drug	2	ST3GAL3, PLCB1
E	Difficult family or no structure, no drug	9	STXBP1, CNPY3, BRWD3, ARX, PHACTR1, GUF1, WDR45, PIGA, WWOX

Undrugged target profiles

12 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ARX	0	CDKL5
STXBP1	1	—
ST3GAL3	2	—
CNPY3	1	—
PLCB1	11	—
BRWD3	5	—
PHACTR1	0	—
GUF1	0	—
WDR45	0	—
PIGA	0	—
UGDH	1	—
WWOX	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 27.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	11
PHASE3	5
PHASE2	5
PHASE2/PHASE3	4
PHASE4	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01413711	PHASE4	WITHDRAWN	An Open-Label, Single and Multiple Oral Dose Pharmacokinetic Study of Vigabatrin in Infants With Infantile Spasms
NCT02092883	PHASE4	COMPLETED	Evaluation of Neuroinflammation in Children With Infantile Spasms
NCT05279118	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome
NCT06201897	PHASE2/PHASE3	RECRUITING	Cortical Excitability in West Syndrome Using Transcranial Magnetic Stimulation
NCT01006811	PHASE2/PHASE3	COMPLETED	Use of the Modified Atkins Diet in Infantile Spasms
NCT01549288	PHASE2/PHASE3	WITHDRAWN	Trial of the Modified Atkins Diet in Infantile Spasms Refractory to Hormonal Therapy
NCT01575639	PHASE3	COMPLETED	Prednisolone in Infantile Spasms- High Dose Versus Usual Dose
NCT01828437	PHASE3	COMPLETED	Addition of Pyridoxine to Prednisolone in Infantile Spasms
NCT02299115	PHASE3	WITHDRAWN	Prednisolone Versus Vigabatrin in the First-line Treatment of Infantile Spasms
NCT02953548	PHASE3	COMPLETED	Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms (GWPCARE7)
NCT02954887	PHASE3	COMPLETED	Phase 3 Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms: Open-label Extension Phase (GWPCARE7)
NCT06819670	PHASE2	RECRUITING	A Study to Prevent Infantile Spasms Relapse
NCT00441896	PHASE2	COMPLETED	A Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms
NCT00442104	PHASE2	TERMINATED	Open-label Extension to Protocol 1042-0500
NCT02829827	PHASE2	TERMINATED	A Phase 2 Study of Radiprodil in Subjects With Drug-resistant Infantile Spasms (IS)
NCT03976076	PHASE2	TERMINATED	A Study of Orally Administered JBPOS0101 in Refractory Infantile Spasms Patients
NCT04302116	Not specified	RECRUITING	Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm
NCT05126914	Not specified	RECRUITING	Multicentre Real-life Follow-up Study of Rare Epileptic Syndromes in Children and Adolescents
NCT00001325	Not specified	COMPLETED	Metabolic Abnormalities in Children With Epilepsy
NCT00552045	Not specified	COMPLETED	Epilepsy Phenome/Genome Project
NCT00968136	Not specified	COMPLETED	Short-term Ketogenic Diet as Compared With Conventional Long-term Trial in Refractory Infantile Spasms: A Randomized, Controlled Study
NCT01073579	Not specified	COMPLETED	Sabril Patient Registry
NCT01367964	Not specified	UNKNOWN	Prevention of West Syndrome With Low-dose Adrenocorticotropin Hormone (ACTH)
NCT01723787	Not specified	COMPLETED	Genetic Studies in Patients and Families With Infantile Spasms
NCT02220114	Not specified	COMPLETED	Acceptability Study of a New Paediatric Form of Vigabatrin in Infants and Children With Infantile Spasms or Pharmacoresistant Partial Epilepsy
NCT02885389	Not specified	COMPLETED	Molecular Genetics in Infantile Spasms
NCT06315829	Not specified	COMPLETED	Artificial Intelligence-based Video Analysis to Detect Infantile Spasms

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PREDNISOLONE	4	5
CORTICOTROPIN	4	4
VIGABATRIN	4	3
CANNABIDIOL	4	2
GANAXOLONE	4	2
FAMOTIDINE	4	1
JBPOS-0101	2	1
RADIPRODIL	2	1
CHEMBL3274100	0	1