{"orpha":280633,"name":"Multiple congenital anomalies-hypotonia-seizures syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Congenital disorder of glycosylation due to PIGN deficiency","PIGN-CDG"],"definition":"A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by severe global developmental delay, hypotonia, and early-onset seizures, associated with multiple congenital anomalies, such as cardiac (e.g. patent foramen ovale, atrial septal defect, patent ductus arteriosus), genitourinary (i.e. hydrocele, renal collecting system dilatation, hydroureter, hydronephrosis, hypertrophic trabecular urinary bladder) and gastrointestinal abnormalities (including gastroesophageal reflux, anal stenosis, imperforate anus, ano-vestibular fistula), as well as facial dysmorphism which includes coarse facies, a prominent occiput, bitemporal narrowing, epicanthal folds, hypertelorism, nystagmus/strabismus/wandering eyes, low-set, large ears with auricle abnormalities, depressed nasal bridge, upturned nose, long philtrum, large, open mouth with thin lips, high-arched palate, and micro/retrognathia.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-280633/","orphanet_url":"https://www.orpha.net/en/disease/detail/280633","names":{"fr":{"name":"Syndrome d'anomalies congénitales multiples-hypotonie-épilepsie","synonyms":["Anomalie congénitale de la glycosylation par déficit en PIGN","PIGN-CDG"],"definition":"Syndrome rare, génétique, d'anomalies congénitales multiples/dysmorphie, caractérisé par un retard de développement global sévère, une hypotonie et des crises d'épilepsie précoces, associé à des anomalies congénitales multiples, telles que des anomalies cardiaques (par ex. hydrocèle, dilatation du système collecteur rénal, la distension de l'uretère, hydronéphrose, vessie trabéculaire hypertrophique) et des anomalies gastro-intestinales (y compris le reflux gastro-oesophagien, la sténose anale, l'anus imperforé, la fistule ano-vestibulaire), ainsi qu'une dysmorphie faciale se traduisant par des traits du visage grossiers, un occiput proéminent, un rétrécissement bitemporal, des plis épicanthaux, un hypertélorisme, un nystagmus/strabisme/ exotropie (oeil errant), des grandes oreilles implantées bas avec des anomalies du pavillon, un pont nasal déprimé, un nez retroussé, un long philtrum, une bouche grande et ouverte avec des lèvres minces, un palais ogival et une micro/rétrognathie."},"de":{"name":"Multiple kongenitale Anomalien-Hypotonie-Krampfanfälle-Syndrom","synonyms":["Glykosylierungs-Krankheit, kongenitale, durch PIGN-Mangel","Kohlenhydrat-defizientes Glykoprotein-Syndrom durch PIGN-Mangel","Kongenitaler Defekt der Glycoproteinbiosynthese durch PIGN-Mangel","MCAHS1","PIGN-CDG"],"definition":"Ein genetisch bedingtes Dysmorphie-Syndrom, das durch eine schwere globale Entwicklungsverzögerung, Hypotonie und früh einsetzende Krämpfe gekennzeichnet ist und mit multiplen kongenitalen Anomalien einhergeht, wie Herzfehler (z.B. offenes Foramen ovale, Vorhofseptumdefekt, offener Ductus arteriosus), Urogenitalfehlbildungen (z.B. Hydrozele, Erweiterung des Nierensammelsystems, Hydroureter, Hydronephrose, hypertrophische trabekuläre Harnblase) und gastrointestinalen Fehlbildungen (einschließlich gastroösophagealer Reflux, Analstenose, Analatresie, ano-vestibuläre Fistel). Weitere Merkmale sind Gesichtsdysmorphien (grobe Gesichtszüge, hervorstehendes Hinterhaupt, Epikanthusfalten, Hypertelorismus, Nystagmus/Strabismus/Wanderaugen, tief angesetzte, große Ohren mit Anomalien der Ohrmuschel, einen vertieften Nasenrücken, eine nach oben gebogene Nase, ein langes Philtrum, einen großen, offenen Mund mit dünnen Lippen, hochgewölbter Gaumen und Mikro-/Retrognathie)."},"es":{"name":"Síndrome de anomalías congénitas múltiples-hipotonía-epilepsia","synonyms":["PIGN-CDG","Trastorno congénito de la glicosilación por deficiencia de PIGN"],"definition":"Es un síndrome dismórfico/de múltiples anomalías congénitas, de origen genético y poco frecuente, caracterizado por grave retraso global del desarrollo, hipotonía y convulsiones de inicio temprano, asociadas a múltiples anomalías congénitas tales como anomalías cardíacas (p. ej, foramen oval permeable, comunicación interauricular, ductus arterioso persistente), genitourinarias (hidrocele, dilatación del sistema colector renal, hidrouréter, hidronefrosis, vejiga trabeculada hipertrófica) y gastrointestinales (incluyendo reflujo gastroesofágico, estenosis anal, ano imperforado, fístula ano-vestibular), así como dismorfia facial que incluye cara tosca, occipucio prominente, estrechamiento bitemporal, pliegues epicánticos, hipertelorismo, nistagmo/estrabismo/ojos errantes, orejas grandes de implantación baja con anomalías del pabellón auricular, puente nasal deprimido, nariz respingona, filtrum largo, boca grande y abierta con labios finos, paladar ojival y micro-/retrognatia."},"it":{"name":"Sindrome anomalie congenite multiple-ipotonia-crisi epilettiche","definition":"Si tratta di una malattia genetica rara da anomalie/dismorfismi congeniti multipli, caratterizzata da grave ritardo dello sviluppo globale, ipotonia e crisi epilettiche ad esordio precoce, associate ad anomalie congenite multiple, che comprendono le cardiopatie (ad es. forame ovale pervio, difetto del setto interatriale, dotto arterioso pervio), le anomalie genitourinarie (idrocele, dilatazione del sistema collettore renale, idrouretere, idronefrosi, vescica trabecolare ipertrofica), le anomalie gastrointestinali (reflusso gastroesofageo, stenosi anale, ano imperforato, fistola ano-vestibolare), i dismorfismi facciali (aspetto grossolano del viso, occipite prominente, restringimento bitemporale, epicanto, ipertelorismo, nistagmo/strabismo/occhi erranti, orecchie grandi a basso impianto con anomalie del padiglione, sella nasale infossata, naso rivolto verso l'alto, filtro lungo, bocca grande e aperta con labbra sottili, palato ogivale e micro/retrognazia)."},"nl":{"name":"Multipele congenitale anomalieën - hypotonie - insulten-syndroom","synonyms":["Congenitale defecten van de glycosylering door PIGN-deficiëntie","Congenitale glycosylatiestoornis door PIGN-deficiëntie","Meervoudige aangeboren afwijkingen - hypotonie - insulten-syndroom","PIGN-CDG"],"definition":"Een zeldzaam, genetisch syndroom met multipele congenitale anomalieën/dysmorfie, gekenmerkt door ernstige algehele ontwikkelingsachterstand, hypotonie, en vroeg optredende insulten, geassocieerd met multipele congenitale anomalieën, zoals cardiale (e.g. persisterend foramen ovale, atriumseptumdefect, persisterende ductus arteriosus), urogenitale (i.e. hydrocele, dilatatie van verzamelsysteem van nier, hydro-ureter, hydronefrose, hypertrofische trabekelblaas) en gastro-intestinale (waaronder gastro-oesofageale reflux, anale stenose, anusatresie, ano-vestibulaire fistel) afwijkingen, alsook faciale dysmorfie met onder meer grof gelaat, prominent achterhoofd, bitemporale vernauwing, epicanthusplooien, hypertelorisme, nystagmus/strabisme/dwalende ogen, laagstaande en grote oren met abnormale oorschelp, ingezakte neusbrug, wipneus, lang filtrum, grote en open mond met dunne lippen, hoog gebogen gehemelte, en micro-/retrognathie."},"pt":{"name":"Síndrome de anomalias congénitas múltiplas-hipotonia-convulsões","definition":"Síndrome dismórfica / anomalias congénitas múltiplas, genética, rara, caracterizada por perturbação grave do desenvolvimento global, hipotonia e convulsões de início precoce, associada a múltiplas anomalias congénitas, a nível cardíaco (por exemplo, forame oval patente, defeito do septo atrial, persistência do canal arterial), geniturinário (ou seja, hidrocelo, dilatação do sistema coletor renal, hidroureter, hidronefrose, bexiga trabecular hipertrófica) e anomalias gastrointestinais (incluindo refluxo gastroesofágico, estenose anal, ânus imperfurado, fístula ano-vestibular), ocorre também dismorfia facial, que inclui fácies grosseira, occipital proeminente, estreitamento bitemporal, epicantus, hipertelorismo, nistagmo / estrabismo / olhar não estável, inserção baixa, orelhas de tamanho aumentado com anomalias auriculares, ponte nasal deprimida, nariz arrebitado, filtro longo, boca grande e aberta com lábios finos, palato arqueado alto e micro / retrognatia."},"pl":{"name":"Zespół mnogie wady wrodzone - hipotonia - drgawki","synonyms":["Congenital disorder of glycosylation due to PIGN deficiency","PIGN-CDG"]},"cs":{"name":"Syndrom zahrnující mnohočetné vrozené vývojové vady, hypotonii a záchvaty","synonyms":["Congenital disorder of glycosylation due to PIGN deficiency","PIGN-CDG"]},"uk":{"name":"Синдром множинних вроджених аномалій-гіпотонії-судом","synonyms":["Вроджене порушення глікозилювання внаслідок дефіциту PIGN","PIGN-CDG"],"definition":"A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by severe global developmental delay, hypotonia, and early-onset seizures, associated with multiple congenital anomalies, such as cardiac (e.g. patent foramen ovale, atrial septal defect, patent ductus arteriosus), genitourinary (i.e. hydrocele, renal collecting system dilatation, hydroureter, hydronephrosis, hypertrophic trabecular urinary bladder) and gastrointestinal abnormalities (including gastroesophageal reflux, anal stenosis, imperforate anus, ano-vestibular fistula), as well as facial dysmorphism which includes coarse facies, a prominent occiput, bitemporal narrowing, epicanthal folds, hypertelorism, nystagmus/strabismus/wandering eyes, low-set, large ears with auricle abnormalities, depressed nasal bridge, upturned nose, long philtrum, large, open mouth with thin lips, high-arched palate, and micro/retrognathia."},"zh":{"name":"多重先天性异常-肌张力低下-癫痫综合征","synonyms":["PIGN缺陷所致先天性糖基化障碍"],"definition":"多发性先天性畸形-肌无力-惊厥综合征是一种罕见的遗传性多发性先天畸形综合征，其特征是严重的全面发育迟缓、肌张力低下和早发性惊厥，并伴有多发性先天性畸形，如心脏（如卵圆孔未闭、房间隔缺损、动脉导管未闭）、泌尿生殖系统（如鞘膜积液、肾集合系统扩张、输尿管积水、肾积水、尿道膀胱肌小梁肥大）和胃肠道畸形（包括胃食管反流、肛门狭窄、肛门闭锁、肛门-前庭瘘），面部畸形，包括面容粗糙、枕骨突出、双侧颞部狭窄，内眦皱襞、眼距过宽、眼球震颤/斜视/走神、低位耳伴大耳廓畸形、鼻梁凹陷、鼻孔外翻、长人中、大张口伴薄唇、高腭弓和小退缩下颌。"},"tr":{"name":"Çoklu doğumsal anomaliler-hipotoni-nöbet sendromu","synonyms":["PIGN-CDG","PIGN eksikliğine bağlı doğumsal glikozilasyon bozukluğu"]}},"xrefs":[{"source":"OMIM","code":"614080","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD2F.1Y","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0013563","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5191419","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"12781","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":371235,"name":"Congenital disorder of glycosylation with developmental anomaly","classifications":[147,156]},{"orpha":371071,"name":"Congenital disorder of glycosylation with epilepsy as a major feature","classifications":[156,181]},{"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]}],"children":[],"genes":[{"symbol":"PIGN","name":"phosphatidylinositol glycan anchor biosynthesis class N","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21493957[PMID]","hgnc":"8967","ensembl":"ENSG00000197563","omim":"606097","loci":["18q21.33"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Antenatal","Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":15.0,"area":"Worldwide","status":"Validated","source":"26394714[PMID]_26364997[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_26394714[PMID]_26364997[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-02-06","source":"21493957[PMID]_26364997[PMID]_26394714[PMID]_26419326[PMID]_24253414[PMID]","terms":[{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011344","label":"Severe global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0006829","label":"Severe muscular hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001156","label":"Brachydactyly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000280","label":"Coarse facial features","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001615","label":"Hoarse cry","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001265","label":"Hyporeflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004488","label":"Macrocephaly at birth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001655","label":"Patent foramen ovale","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010291","label":"Prominent palatine ridges","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011247","label":"Prominent superior crus of antihelix","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001773","label":"Short foot","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0200055","label":"Small hand","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001182","label":"Tapered finger","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001337","label":"Tremor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004742","label":"Abnormal renal collecting system morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000932","label":"Abnormality of the posterior cranial fossa","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000646","label":"Amblyopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002023","label":"Anal atresia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002025","label":"Anal stenosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002616","label":"Aortic root aneurysm","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011333","label":"Asymmetric crying face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002305","label":"Athetosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001631","label":"Atrial septal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000498","label":"Blepharitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008676","label":"Congenital megaureter","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004681","label":"Deep longitudinal plantar crease","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006254","label":"Elevated alpha-fetoprotein","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000565","label":"Esotropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002286","label":"Fair hair","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005830","label":"Flexion contracture of toe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000293","label":"Full cheeks","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003324","label":"Generalized muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000212","label":"Gingival overgrowth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000034","label":"Hydrocele testis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000126","label":"Hydronephrosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000072","label":"Hydroureter","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007441","label":"Hyperpigmented/hypopigmented macules","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001804","label":"Hypoplastic fingernail","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010880","label":"Increased nuchal translucency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002265","label":"Large fleshy ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000308","label":"Microretrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008551","label":"Microtia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000774","label":"Narrow chest","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000160","label":"Narrow mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000396","label":"Overfolded helix","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002951","label":"Partial absence of cerebellar vermis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001643","label":"Patent ductus arteriosus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004969","label":"Peripheral pulmonary artery stenosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001761","label":"Pes cavus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000269","label":"Prominent occiput","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011271","label":"Prominent tragus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006165","label":"Proportionate shortening of all digits","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008994","label":"Proximal muscle weakness in lower limbs","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002092","label":"Pulmonary arterial hypertension","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025025","label":"Rectovestibular fistula","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002100","label":"Recurrent aspiration pneumonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001667","label":"Right ventricular hypertrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003196","label":"Short nose","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000350","label":"Small forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000319","label":"Smooth philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000664","label":"Synophrys","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010804","label":"Tented upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010282","label":"Thin lower lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000219","label":"Thin upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008718","label":"Unilateral renal dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008635","label":"Urinary bladder wall hypertrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010544","label":"Vertical nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000154","label":"Wide mouth","frequency":"Occasional (29-5%)","criteria":null}]}}