{"orpha":369837,"name":"Intellectual disability-seizures-hypophosphatasia-ophthalmic-skeletal anomalies syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Congenital disorder of glycosylation due to PIGT deficiency","MCAHS type 3","Multiple congenital anomalies-hypotonia-seizures syndrome type 3","PIGT-CDG"],"definition":"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.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-369837/","orphanet_url":"https://www.orpha.net/en/disease/detail/369837","names":{"fr":{"name":"Syndrome de déficience intellectuelle-épilepsie-hypophosphatasie-anomalies ophtalmiques et squelettiques","synonyms":["Anomalie congénitale de la glycosylation par déficit en PIGT","MCAHS type 3","PIGT-CDG","Syndrome d'anomalies congénitales multiples-hypotonie-épilepsie type 3"],"definition":"Anomalie congénitale rare de la glycosylation caractérisée par une hypotonie néonatale, un retard de développement global, une régression dans le processus de développement et une déficience intellectuelle sévère à profonde, des convulsions fébriles infantiles, survenant par la suite sans raison apparente, des troubles de la vision avec ésotropie et nystagmus, atrophie cérébrale et cérébelleuse progressive, anomalies squelettiques (y compris brachycéphalie, scoliose, os longs fins, âge osseux retardé, pectus excavatum et ostéopénie), des mamelons inversés et une dysmorphie faciale à type de front haut, étroit et proéminent, de nez court, d'arête nasale déprimée, de narines antéversées, de palais arqué et de bouche grande ouverte en raison d'une diminution du tonus musculaire facial. D'autres caractéristiques peuvent inclure des anomalies cardiaques (persistance du canal artériel, malformations septales auriculaires), des anomalies urogénitales (néphrocalcinose, urolithiase) et un faible taux de phosphatase alcaline sérique."},"de":{"name":"Intelligenzminderung-Krämpfe-Hypophosphatasie-ophthalmologische und skelettale Anomalien-Syndrom","synonyms":["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"],"definition":"Eine seltene kongenitale Glykosylierungsstörung, die durch neonatale Hypotonie, globale Entwicklungsverzögerung, Entwicklungsrückgang und schwere bis hochgradige Intelligenzminderung gekennzeichnet ist. Charakteristische Merkmale sind Anfälle im Kindesalter, die zunächst mit Fieberkrämpfen einhergehen und anschließend in unprovozierte Anfälle übergehen, Sehstörungen mit Esotropie und Nystagmus, fortschreitende zerebrale und zerebelläre Atrophie, Skelettanomalien (einschließlich Brachyzephalie, Skoliose, schlanke lange Knochen, verzögertes Knochenalter, Trichterbrust und Osteopenie), Hohlwarzen und Dysmorphien wie hohe und schmale Stirn, Balkonstirn, kurze Nase, flache Nasenbrücke, antevertierte Nasenlöcher, hoher Gaumen und weit geöffneter Mund (kennzeichnend für faziale Hypotonie). Weitere Merkmale können Herzanomalien (wie offener Ductus arteriosus, Vorhofseptumdefekte), urogenitale Anomalien (wie Nephrokalzinose, Urolithiasis) und eine niedrige Plasmakonzentration der alkalischen Phosphatase sein."},"es":{"name":"Síndrome de discapacidad intelectual-crisis-hipofosfatasia-anomalías oftalmológicas y esqueléticas","synonyms":["MCAHS tipo 3","PIGT-CDG","Síndrome de anomalías congénitas múltiples-hipotonía-crisis tipo 3","Trastorno congénito de la glicosilación por deficiencia de PIGT"],"definition":"Es un trastorno congénito poco frecuente de glicosilación caracterizado por hipotonía neonatal, retraso global / regresión del desarrollo y discapacidad intelectual de grave a profunda, convulsiones de inicio en la lactancia asociadas inicialmente a episodios febriles con transición posterior a convulsiones no provocadas, visión deficiente con esotropia y nistagmo, atrofia cerebral y cerebelosa progresiva, anomalías esqueléticas (que incluyen braquicefalia, escoliosis, huesos largos delgados, retraso de la edad ósea, pectus excavatum y osteopenia), pezones invertidos y características dismórficas que incluyen frente alta y estrecha, protuberancia frontal, nariz corta, puente nasal deprimido, narinas antevertidas, paladar alto y boca abierta, congruente con hipotonía facial. Otras características pueden incluir anomalías cardíacas (tales como conducto arterioso persistente, comunicación interauricular), anomalías urogenitales (tales como nefrocalcinosis, urolitiasis) y baja concentración plasmática de fosfatasa alcalina."},"it":{"name":"Sindrome da disabilità intellettiva, crisi epilettiche, ipotonia e anomalie oculari e scheletriche","definition":"La sindrome da disabilità intellettiva, crisi epilettiche, ipotonia e anomalie oculari e scheletriche è una malattia congenita rara della glicosilazione, caratterizzata da ipotonia neonatale, ritardo dello sviluppo globale, regressione dello sviluppo, disabilità intellettiva grave o molto grave, crisi epilettiche ad esordio neonatale, inizialmente associate ad episodi febbrili e successivamente non associate a fattori scatenanti, compromissione della vista con esotropia e nistagmo, atrofia cerebrale e cerebellare progressiva, anomalie scheletriche (brachicefalia, scoliosi, assottigliamento delle ossa lunghe, ritardo dell'età ossea, pectus excavatum e osteopenia), capezzoli introflessi e dismorfismi (fronte alta, stretta e bombata, naso corto con sella infossata, narici anteverse, palato ogivale e bocca aperta secondaria all'ipotonia facciale). Altri segni clinici sono le cardiopatie (dotto arterioso pervio, difetti del setto interatriale), le anomalie urogenitali (nefrocalcinosi, urolitiasi) e una bassa concentrazione di fosfatasi alcalina nel plasma."},"nl":{"name":"Intellectuele achterstand - insulten - hypofosfatasie - oftalmische-skeletale anomalieën-syndroom","synonyms":["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"],"definition":"Een zeldzame, congenitale glycosylatiestoornis, gekenmerkt door neonatale hypotonie, algehele ontwikkelingsachterstand, ontwikkelingsregressie en ernstige tot zware intellectuele achterstand, infantiel optredende insulten die initieel geassocieerd zijn met febriele episodes en vervolgens overgaan in niet-uitgelokte insulten, verstoord zicht met esotropie en nystagmus, progressieve cerebrale en cerebellaire atrofie, skeletafwijkingen (onder meer brachycefalie, scoliose, tengere pijpbeenderen, vertraagde botmaturatie, pectus excavatum (trechterborst) en osteopenie), geïnverteerde tepels en dysmorfe kenmerken waaronder hoog en smal voorhoofd, boller voorhoofd, korte neus, ingezakte neusbrug, anteversie van neusgaten, hoog gehemelte en wijd open mond consistent met faciale hypotonie. Andere mogelijke kenmerken zijn onder meer hartafwijkingen (zoals persisterende ductus arteriosus, atriumseptumdefecten), urogenitale anomalieën (zoals nefrocalcinose, urolithiasis), en lage concentratie van alkalische fosfatase in plasma."},"pt":{"name":"Síndrome de perturbação do desenvolvimento intelectual-convulsões-hipofosfatemia-anomalias oftalmológicas e esqueléticas"},"pl":{"name":"Zespół niepełnosprawność intelektualna-napady padaczkowe-hipotonia-wady oczu-wady kostne","synonyms":["Congenital disorder of glycosylation due to PIGT deficiency","MCAHS type 3","Multiple congenital anomalies-hypotonia-seizures syndrome type 3","PIGT-CDG"],"definition":"*Zespół niepełnosprawność intelektualna-napady padaczkowe-hipotonia-wady oczu-wady kostne jest rzadkim wrodzonym zaburzeniem glikozylacji, który charakteryzuje się hipotonią noworodków, całościowym opóźnieniem rozwoju, regresem rozwoju i ciężką lub głęboką niepełnosprawnością intelektualną, napadami padaczkowymi o początku w okresie niemowlęcym, początkowo o charakterze drgawek gorączkowych, które z czasem przybierają postać napadów drgawkowych występujących bez uchwytnej przyczyny, zaburzeniami widzenia z zezem i oczopląsem, postępującym zanikiem mózgu i móżdżku, nieprawidłowościami szkieletowymi (krótkogłowie, skolioza, smukłe kości długie, opóźniony wiek kostny, szewska klatka piersiowa i osteopenia), wciągniętymi brodawkami sutkowymi i cechami dysmorficznymi, takimi jak wysokie i zwężone i wypukłe czoło, krótki nos, zapadnięty grzbiet nosa, odwrócone nozdrza, wysokie podniebienie i szeroko otwarte usta wskutek obniżonego napięcia mięśni twarzy. Inne cechy to: wady serca (przetrwały przewód tętniczy, wady przegrody międzyprzedsionkowej), nieprawidłowości układu moczowo-płciowego (wapnica nerek, kamica układu moczowego) oraz niskie stężenie fosfatazy alkalicznej w surowicy krwi."},"cs":{"name":"Syndrom zahrnující mentální retardaci, záchvaty, hypotonii a oční a kostní anomálie","synonyms":["Congenital disorder of glycosylation due to PIGT deficiency","MCAHS type 3","Multiple congenital anomalies-hypotonia-seizures syndrome type 3","PIGT-CDG"]},"uk":{"name":"Синдром інтелектуальної недостатності-судом-гіпофосфатазії-офтальмологічних та скелетних аномалій","synonyms":["Вроджене порушення глікозилювання внаслідок дефіциту PIGT","MCAHS тип 3","Синдром множинних вроджених аномалій-гіпотонії-судом типу 3","PIGT-CDG"],"definition":"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."},"zh":{"name":"智力障碍-癫痫-低磷酸酶-眼-骨骼异常综合征","synonyms":["MCAHS3型"],"definition":"智力障碍-癫痫发作-张力减退-眼-骨骼异常综合征是一种罕见的先天性糖基化障碍，其特征是新生儿期肌张力低下、全面发育迟缓、发育倒退和重至极重度的智力障碍、婴儿期发作的癫痫（最初与发热发作有关，随后转变为无关）、视力受损并伴有内斜视和眼球震颤，进行性大脑和小脑萎缩，骨骼异常(包括短头畸形、脊柱侧凸、长骨细长、骨龄延迟、漏斗胸和骨质减少)、乳头内陷和畸形特征（包括高窄额头、额头隆起、短鼻、鼻梁凹陷、鼻孔前倾、上颚高张及面肌张力低下所致张口畸形）。本病的其他特征包括心脏异常(如动脉导管未闭、房间隔缺损)、泌尿生殖系统异常(如肾钙化、泌尿系结石)和低血浆碱性磷酸酶浓度。"},"tr":{"name":"Zihinsel yetersizlik-nöbetler-hipofosfatazi-oftalmik-iskelet anomalileri sendromu","synonyms":["PIGT eksikliğine bağlı doğumsal glikozilasyon bozukluğu","Çoklu doğumsal anomaliler-hipotoni-nöbet sendromu tip 3","PIGT-CDG","MCAHS tip 3"]}},"xrefs":[{"source":"OMIM","code":"615398","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E77.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C52.Y","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0014165","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4749459","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":371195,"name":"Congenital disorder of glycosylation-related bone disorder","classifications":[147,156]},{"orpha":309515,"name":"Disorder of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation","classifications":[150,156]},{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":139393,"name":"Syndromic craniosynostosis","classifications":[147,156,199]}],"children":[],"genes":[{"symbol":"PIGT","name":"phosphatidylinositol glycan anchor biosynthesis class T","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23636107[PMID]","hgnc":"14938","ensembl":"ENSG00000124155","omim":"610272","loci":["20q13.12"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":4.0,"area":"Worldwide","status":"Validated","source":"23636107[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-11-20","source":"25943031[PMID]_28728837[PMID]","terms":[{"hpo":"HP:0011842","label":"Abnormality of skeletal morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000248","label":"Brachycephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0100704","label":"Cerebral visual impairment","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0005280","label":"Depressed nasal bridge","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000348","label":"High forehead","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000341","label":"Narrow forehead","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000938","label":"Osteopenia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003100","label":"Slender long bone","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012373","label":"Abnormal eye physiology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001627","label":"Abnormal heart morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000079","label":"Abnormality of the urinary system","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002069","label":"Bilateral tonic-clonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008676","label":"Congenital megaureter","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003282","label":"Decreased circulating alkaline phosphatase activity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002750","label":"Delayed skeletal maturation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002714","label":"Downturned corners of mouth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002123","label":"Generalized myoclonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010818","label":"Generalized tonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002705","label":"High, narrow palate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003072","label":"Hypercalcemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002150","label":"Hypercalciuria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000540","label":"Hypermetropia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000121","label":"Nephrocalcinosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000767","label":"Pectus excavatum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009824","label":"Upper limb undergrowth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002101","label":"Abnormal lung lobation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000483","label":"Astigmatism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001631","label":"Atrial septal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010536","label":"Central sleep apnea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001363","label":"Craniosynostosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002720","label":"Decreased circulating IgA level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002850","label":"Decreased circulating total IgM","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025330","label":"Downgaze palsy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011199","label":"EEG with generalized sharp slow waves","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010850","label":"EEG with spike-wave complexes","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002263","label":"Exaggerated cupid's bow","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002121","label":"Generalized non-motor (absence) seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002283","label":"Global brain atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002155","label":"Hypertriglyceridemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000829","label":"Hypoparathyroidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003186","label":"Inverted nipples","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006961","label":"Jerky head movements","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000272","label":"Malar flattening","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012718","label":"Morphological abnormality of the gastrointestinal tract","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010841","label":"Multifocal epileptiform discharges","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011470","label":"Nasogastric tube feeding in infancy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001513","label":"Obesity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002870","label":"Obstructive sleep apnea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001643","label":"Patent ductus arteriosus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030856","label":"Posterior staphyloma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000826","label":"Precocious puberty","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006480","label":"Premature loss of teeth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000107","label":"Renal cyst","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000110","label":"Renal dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001723","label":"Restrictive cardiomyopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010804","label":"Tented upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Occasional (29-5%)","criteria":null}]}}