ORPHA:369837
Intellectual disability-seizures-hypophosphatasia-ophthalmic-skeletal anomalies syndrome
Synonyms: Congenital disorder of glycosylation due to PIGT deficiency · MCAHS type 3 · Multiple congenital anomalies-hypotonia-seizures syndrome type 3 · PIGT-CDG
- Type
- Malformation syndrome
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Infancy, Neonatal
- Status
- active
A rare congenital disorder of glycosylation characterized by neonatal hypotonia, global development delay, developmental regress and severe to profound intellectual disability, infantile onset seizures that are initially associated with febrile episodes with subsequent transition to unprovoked seizures, impaired vision with esotropia and nystagmus, progressive cerebral and cerebellar atrophy, skeletal abnormalities (including brachycephaly, scoliosis, slender long bones, delayed bone age, pectus excavatum and osteopenia), inverted nipples and dysmorphic features including high and narrow forehead, frontal bossing, short nose, depressed nasal bridge, anteverted nares, high palate and wide open mouth consistent with facial hypotonia. Other features may include cardiac abnormalities (such as patent ductus arteriosus, atrial septal defects), urogenital abnormalities (such as nephrocalcinosis, urolithiasis), and low plasma concentration of alkaline phosphatase.
1
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Intellectual disability-seizures-hypophosphatasia-ophthalmic-skeletal anomalies syndrome | Congenital disorder of glycosylation due to PIGT deficiency · MCAHS type 3 · Multiple congenital anomalies-hypotonia-seizures syndrome type 3 · PIGT-CDG |
| fr | Syndrome de déficience intellectuelle-épilepsie-hypophosphatasie-anomalies ophtalmiques et squelettiques | Anomalie congénitale de la glycosylation par déficit en PIGT · MCAHS type 3 · PIGT-CDG · Syndrome d'anomalies congénitales multiples-hypotonie-épilepsie type 3 |
| de | Intelligenzminderung-Krämpfe-Hypophosphatasie-ophthalmologische und skelettale Anomalien-Syndrom | Glykosylierungs-Krankheit, kongenitale, durch PIGT-Mangel · Kohlenhydrat-defizientes Glykoprotein-Syndrom durch PIGT-Mangel · Kongenitaler Defekt der Glycoproteinbiosynthese durch PIGT-Mangel · MCAHS Typ 3 · Multiple kongenitale Anomalien-Hypotonie-Krämpfe-Syndrom Typ 3 · PIGT-CDG |
| es | Síndrome de discapacidad intelectual-crisis-hipofosfatasia-anomalías oftalmológicas y esqueléticas | MCAHS tipo 3 · PIGT-CDG · Síndrome de anomalías congénitas múltiples-hipotonía-crisis tipo 3 · Trastorno congénito de la glicosilación por deficiencia de PIGT |
| it | Sindrome da disabilità intellettiva, crisi epilettiche, ipotonia e anomalie oculari e scheletriche | |
| nl | Intellectuele achterstand - insulten - hypofosfatasie - oftalmische-skeletale anomalieën-syndroom | Congenitale defecten van de glycosylering door PIGT-deficiëntie · Congenitale glycosylatiestoornis door PIGT-deficiëntie · MCAHS type 3 · Multipele congenitale anomalieën - hypotonie - insulten-syndroom type 3 · PIGT-CDG |
| pt | Síndrome de perturbação do desenvolvimento intelectual-convulsões-hipofosfatemia-anomalias oftalmológicas e esqueléticas | |
| pl | Zespół niepełnosprawność intelektualna-napady padaczkowe-hipotonia-wady oczu-wady kostne | = en |
| cs | Syndrom zahrnující mentální retardaci, záchvaty, hypotonii a oční a kostní anomálie | = en |
| uk | Синдром інтелектуальної недостатності-судом-гіпофосфатазії-офтальмологічних та скелетних аномалій | Вроджене порушення глікозилювання внаслідок дефіциту PIGT · MCAHS тип 3 · Синдром множинних вроджених аномалій-гіпотонії-судом типу 3 · PIGT-CDG |
| zh | 智力障碍-癫痫-低磷酸酶-眼-骨骼异常综合征 | MCAHS3型 |
| tr | Zihinsel yetersizlik-nöbetler-hipofosfatazi-oftalmik-iskelet anomalileri sendromu | PIGT eksikliğine bağlı doğumsal glikozilasyon bozukluğu · Çoklu doğumsal anomaliler-hipotoni-nöbet sendromu tip 3 · PIGT-CDG · MCAHS tip 3 |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 615398 | E | validated | |
| ICD-10 | E77.8 | NTBT | attributed | validated |
| ICD-11 | 5C52.Y | NTBT | attributed | validated |
| MONDO | 0014165 | E | validated | |
| UMLS | C4749459 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
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Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (6):
- ORPHA:371195Congenital disorder of glycosylation-related bone disorder
rare developmental anomalies during embryogenesis; rare genetic diseases - ORPHA:309515Disorder of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation
rare inborn errors of metabolism; rare genetic diseases - ORPHA:611327Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare genetic diseases - ORPHA:102283Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare developmental anomalies during embryogenesis; rare neurological diseases - ORPHA:68385Neurometabolic disease
rare genetic diseases; rare neurological diseases - ORPHA:139393Syndromic craniosynostosis
rare developmental anomalies during embryogenesis; rare genetic diseases; rare bone diseases
No children.
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Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| PIGT | Disease-causing germline mutation(s) in | Assessed | HGNC:14938 | ENSG00000124155 | 610272 | 20q13.12 | phosphatidylinositol glycan anchor biosynthesis class T | 23636107[PMID] |
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Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 4 cases | Worldwide | Case(s) | Validated | 23636107[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
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HPO phenotypes
71 annotations · validated 2019-11-20| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0011842 | Abnormality of skeletal morphology | |
| HP:0000248 | Brachycephaly | |
| HP:0100704 | Cerebral visual impairment | |
| HP:0005280 | Depressed nasal bridge | |
| HP:0000348 | High forehead | |
| HP:0001252 | Hypotonia | |
| HP:0010864 | Intellectual disability, severe | |
| HP:0000343 | Long philtrum | |
| HP:0000341 | Narrow forehead | |
| HP:0000639 | Nystagmus | |
| HP:0000938 | Osteopenia | |
| HP:0003100 | Slender long bone | |
| HP:0000486 | Strabismus | |
| Frequent (79-30%) | ||
| HP:0012373 | Abnormal eye physiology | |
| HP:0001627 | Abnormal heart morphology | |
| HP:0000079 | Abnormality of the urinary system | |
| HP:0002069 | Bilateral tonic-clonic seizure | |
| HP:0008676 | Congenital megaureter | |
| HP:0003282 | Decreased circulating alkaline phosphatase activity | |
| HP:0002750 | Delayed skeletal maturation | |
| HP:0002714 | Downturned corners of mouth | |
| HP:0002123 | Generalized myoclonic seizure | |
| HP:0010818 | Generalized tonic seizure | |
| HP:0000365 | Hearing impairment | |
| HP:0002705 | High, narrow palate | |
| HP:0003072 | Hypercalcemia | |
| HP:0002150 | Hypercalciuria | |
| HP:0000540 | Hypermetropia | |
| HP:0000121 | Nephrocalcinosis | |
| HP:0000767 | Pectus excavatum | |
| HP:0002650 | Scoliosis | |
| HP:0009824 | Upper limb undergrowth | |
| HP:0000431 | Wide nasal bridge | |
| Occasional (29-5%) | ||
| HP:0002101 | Abnormal lung lobation | |
| HP:0000483 | Astigmatism | |
| HP:0001631 | Atrial septal defect | |
| HP:0010536 | Central sleep apnea | |
| HP:0001272 | Cerebellar atrophy | |
| HP:0001363 | Craniosynostosis | |
| HP:0002720 | Decreased circulating IgA level | |
| HP:0002850 | Decreased circulating total IgM | |
| HP:0025330 | Downgaze palsy | |
| HP:0011199 | EEG with generalized sharp slow waves | |
| HP:0010850 | EEG with spike-wave complexes | |
| HP:0002263 | Exaggerated cupid's bow | |
| HP:0002020 | Gastroesophageal reflux | |
| HP:0002121 | Generalized non-motor (absence) seizure | |
| HP:0002283 | Global brain atrophy | |
| HP:0002155 | Hypertriglyceridemia | |
| HP:0000829 | Hypoparathyroidism | |
| HP:0003186 | Inverted nipples | |
| HP:0006961 | Jerky head movements | |
| HP:0001382 | Joint hypermobility | |
| HP:0000369 | Low-set ears | |
| HP:0000272 | Malar flattening | |
| HP:0000347 | Micrognathia | |
| HP:0012718 | Morphological abnormality of the gastrointestinal tract | |
| HP:0010841 | Multifocal epileptiform discharges | |
| HP:0000545 | Myopia | |
| HP:0011470 | Nasogastric tube feeding in infancy | |
| HP:0001513 | Obesity | |
| HP:0002870 | Obstructive sleep apnea | |
| HP:0001643 | Patent ductus arteriosus | |
| HP:0030856 | Posterior staphyloma | |
| HP:0000826 | Precocious puberty | |
| HP:0006480 | Premature loss of teeth | |
| HP:0000107 | Renal cyst | |
| HP:0000110 | Renal dysplasia | |
| HP:0001723 | Restrictive cardiomyopathy | |
| HP:0010804 | Tented upper lip vermilion | |
| HP:0000582 | Upslanted palpebral fissure | |
Run the differential on the 12 obligate / very frequent terms
Annotation source: 25943031[PMID]_28728837[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/369837
- This record as JSON: /data/d/369837.json