{"orpha":300496,"name":"Multiple congenital anomalies-hypotonia-seizures syndrome type 2","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["MCAHS type 2"],"definition":"A rare, genetic, lethal, neurometabolic malformation syndrome characterized by multiple, variable, congenital cardiac (systolic murmur, atrial septal defect), urinary (duplicated collecting system, vesicoureteral reflux) and central nervous system (thin corpus callosum, cerebellar hypoplasia) malformations associated with neonatal hypotonia, early-onset epileptic encephalopathy, and myoclonic seizures. Craniofacial dysmorphism (prominent occiput, enlarged fontanel, fused metopic suture, upslanted palpebral fissures, overfolded helix, depressed nasal bridge, anteverted nose, malar flattening, microstomy with downturned corners, Pierre-Robin sequence, high arched palate, short neck) and other manifestations (joint contractures, hyperreflexia, dysplastic nails, developmental delay) are also observed.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-300496/","orphanet_url":"https://www.orpha.net/en/disease/detail/300496","names":{"fr":{"name":"Syndrome d'anomalies congénitales multiples-hypotonie-épilepsie type 2","synonyms":["MCAHS type 2"],"definition":"Syndrome d'anomalies neurométaboliques rare, génétique et létal, caractérisé par des malformations multiples, variables, congénitales, cardiaques (souffle systolique, communication interauriculaire), urinaires (système collecteur double, reflux vésico-urétéral) et du système nerveux central (corps calleux mince, hypoplasie cérébelleuse) associées à une hypotonie du nourrisson, une encéphalopathie épileptique à début précoce et des crises myocloniques. On observe également une dysmorphie craniofaciale (occiput proéminent, fontanelle élargie, suture métopique fusionnée, fentes palpébrales inclinées vers le haut, hélix replié, pont nasal déprimé, nez antéversé, aplatissement malaire, microstomie avec commissures inversées, séquence de Pierre-Robin, palais ogival, cou court) et d'autres manifestations (contractures articulaires, hyperréflexie, dysplasie des ongles, retard de développement)."},"de":{"name":"Multiple kongenitale Anomalien-Hypotonie-Krampfanfälle-Syndrom Typ 2","synonyms":["MCAHS Typ 2"],"definition":"Ein tödlich verlaufendes neurometabolisches Syndrom mit multiplen variablen angeborenen Fehlbildungen des Herzens (systolisches Herzgeräusch, Vorhofseptumdefekt), der Harnwege (dupliziertes Sammelsystem, vesikoureteraler Reflux) und des Zentralnervensystems (dünnes Corpus callosum, Kleinhirnhypoplasie. Es geht einher mit neonataler Hypotonie, früh einsetzender epileptischer Enzephalopathie und myoklonischen Anfällen. Kraniofaziale Dysmorphien (vorstehendes Hinterhaupt, vergrößerte Fontanelle, verschmolzene metopische Naht, aufsteigende Lidachsen, übergefaltete Helix, abgesenkter Nasenrücken, antevertierte Nase, unterentwickeltes Jochbein, Mikrostomie mit nach unten gerichteten Mundwinkeln, Pierre-Robin-Sequenz, hochgewölbter Gaumen, kurzer Hals) und andere Manifestationen (Gelenkkontrakturen, Hyperreflexie, dysplastische Nägel, Entwicklungsverzögerung) werden ebenfalls beobachtet."},"es":{"name":"Síndrome de anomalías congénitas múltiples-hipotonía-crisis tipo 2","synonyms":["MCAHS tipo 2"],"definition":"Es un síndrome malformativo neurometabólico, genético, letal y poco frecuente, caracterizado por cardiopatías congénitas múltiples y variables (soplo sistólico, comunicación interauricular), malformaciones urinarias (doble sistema colector, reflujo vesicoureteral) y del sistema nervioso central (adelgazamiento del cuerpo calloso, hipoplasia cerebelosa), asociadas a hipotonía neonatal, encefalopatía epiléptica de inicio temprano y convulsiones mioclónicas. También se observa dismorfia craneofacial (occipucio prominente, fontanela agrandada, sutura metópica fusionada, fisuras palpebrales inclinadas hacia arriba, hélix plegado, puente nasal deprimido, nariz antevertida, aplanamiento malar, microstomía con comisuras hacia abajo, secuencia de Pierre-Robin, paladar ojival, cuello corto). Otras manifestaciones descritas incluyen contracturas articulares, hiperreflexia, displasia ungueal y retraso del desarrollo."},"it":{"name":"Sindrome da anomalie congenite multiple, ipotonia e crisi epilettiche tipo 2","synonyms":["MCAHS, tipo 2"],"definition":"La sindrome che associa anomalie congenite multiple, l'ipotonia e le crisi epilettiche tipo 2 è una malattia neurometabolica malformativa genetica rara e letale, caratterizzata da cardiopatie congenite multiple variabili (soffio sistolico, difetto del setto interatriale), malformazioni urinarie (duplicazione del sistema collettore, reflusso vescico-ureterale) e del sistema nervoso centrale (assottigliamento del corpo calloso, ipoplasia cerebellare), associate ad ipotonia neonatale, encefalopatia epilettica ad esordio precoce e crisi miocloniche. I pazienti presentano anche dismorfismi craniofacciali (occipite prominente, fontanella ampia, fusione della sutura metopica, rime palpebrali oblique verso l'alto, eccessiva plicatura dell'elice, sella nasale infossata, naso anteverso, appiattimento della regione malare, microstomia con angoli della bocca rivolti verso il basso, sequenza di Pierre-Robin, palato ogivale, collo corto) ed altri segni clinici (contratture articolari, iperreflessia, displasia delle unghie, ritardo dello sviluppo)."},"nl":{"name":"Multipele congenitale anomalieën - hypotonie - insulten-syndroom type 2","synonyms":["MCAHS type 2","Meervoudige aangeboren afwijkingen - hypotonie - epileptische aanvallen-syndroom type 2"],"definition":"Een zeldzaam, genetisch, letaal, neurometabool malformatiesyndroom, gekarakteriseerd door meervoudige, variabele, congenitale malformaties van hart (systolisch geruis, atriumseptumdefect), urinewegen (verdubbeld verzamelsysteem, vesico-ureterale reflux) en centraal zenuwstelsel (dun corpus callosum, cerebellaire hypoplasie), geassocieerd met neonatale hypotonie, vroeg aanvangende epileptische encefalopathie, en myoclonische insulten. Craniofaciale dysmorfie (prominent achterhoofd, vergroot fontanel, gefuseerde metopische sutuur, schuin naar boven hellende ooglidspleten, overmatig geplooide helix, ingezakte neusbrug, anteversie van neus, platte jukbeenderen, microstomie met naar beneden gekeerde mondhoeken, Pierre Robin sequentie, hoog gebogen verhemelte, korte nek) en andere manifestaties (gewrichtscontracturen, hyperreflexie, dysplastische nagels, ontwikkelingsachterstand) worden ook waargenomen."},"pt":{"name":"Síndrome de anomalias congénitas múltiplas-hipotonia-convulsões tipo 2"},"pl":{"name":"Zespół mnogie wady wrodzone-hipotonia-drgawki typu 2","synonyms":["MCAHS typu 2"],"definition":"*Zespół mnogie wady wrodzone-hipotonia-drgawki typu 2 to rzadki, genetycznie uwarunkowany, letalny zespół neurometabolicznych wad rozwojowych, który charakteryzuje się mnogimi, różnorodnymi wrodzonymi wadami serca (szmer skurczowy, ubytek przegrody międzyprzedsionkowej), układu moczowego (zdwojenie nerek, refluks pęcherzowo-moczowodowy) i ośrodkowego układu nerwowego (ścieńczałe ciało modzelowate, hipoplazja móżdżku), przebiegających z hipotonią noworodków, encefalopatią padaczkową o wczesnym początku i napadami mioklonicznymi. Ponadto opisywano dysmorfię twarzoczaszki (wydatna potylica, powiększone ciemię, zarośnięty szew czołowy, ustawione skośnie ku górze szpary powiekowe, nadmiernie zagięty obrąbek ucha, obniżony grzbiet nosa, zadarty nos, spłaszczenie policzków, małe usta z kącikami skierowanymi ku dołowi, sekwencja Pierre’a Robina, wysokie podniebienie, krótka szyja) oraz inne objawy (przykurcze stawów, wygórowane odruchy, dysplastyczne paznokcie, opóźnienie rozwoju)."},"cs":{"name":"Syndrom zahrnující mnohočetné vrozené anomálie, hypotonii a záchvaty, typ 2","synonyms":["MCAHS typ 2"]},"uk":{"name":"Синдром множинних вроджених аномалій-гіпотонії-судом, тип 2","synonyms":["MCAHS тип 2"],"definition":"A rare, genetic, lethal, neurometabolic malformation syndrome characterized by multiple, variable, congenital cardiac (systolic murmur, atrial septal defect), urinary (duplicated collecting system, vesicoureteral reflux) and central nervous system (thin corpus callosum, cerebellar hypoplasia) malformations associated with neonatal hypotonia, early-onset epileptic encephalopathy, and myoclonic seizures. Craniofacial dysmorphism (prominent occiput, enlarged fontanel, fused metopic suture, upslanted palpebral fissures, overfolded helix, depressed nasal bridge, anteverted nose, malar flattening, microstomy with downturned corners, Pierre-Robin sequence, high arched palate, short neck) and other manifestations (joint contractures, hyperreflexia, dysplastic nails, developmental delay) are also observed."},"zh":{"name":"多发性先天性畸形-肌张力低下-癫痫综合征2型","synonyms":["多发先天性畸形-肌张力低下-惊厥综合征2型"],"definition":"多发先天畸形-肌张力低下-癫痫综合征2型是一种罕见的、遗传致死性神经代谢畸形综合征，其特征是多发性多发性先天性心脏（收缩期杂音、房间隔缺损）、泌尿系统（集合管系统重复、膀胱输尿管反流）和中枢神经系统（胼胝体变薄、小脑发育不良）畸形伴新生儿低血压、早发性癫痫性脑病和肌阵挛性惊厥。颅面畸形（枕骨突出，囟门增大，融合额头缝，睑裂上斜，耳轮过度卷曲，鼻梁凹陷，朝天鼻，平颧骨，小口下弯，Pierre-Robin序列征，高腭弓，短颈）和其他表现（关节挛缩，反射亢进，指甲发育不良，发育迟缓）。"},"tr":{"name":"Çoklu doğumsal anomaliler-hipotoni-nöbet sendromu tip 2","synonyms":["MCAHS tip 2"]}},"xrefs":[{"source":"OMIM","code":"300868","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":"0010466","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4751110","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"12777","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[{"type":"Moved to","orpha":79022,"name":"Simpson-Golabi-Behmel syndrome type 2","status":"inactive"},{"type":"Referred to","orpha":83648,"name":"OBSOLETE: X-linked recessive intellectual disability-macrocephaly-ciliary dysfunction syndrome","status":"inactive"}],"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":"PIGA","name":"phosphatidylinositol glycan anchor biosynthesis class A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"8957","ensembl":"ENSG00000165195","omim":"311770","loci":["Xp22.2"]}],"genes_via_subtypes":[],"inheritance":["X-linked recessive"],"onset":["Antenatal","Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":24.0,"area":"Worldwide","status":"Validated","source":"16783569[PMID]_22305531[PMID]_24357517[PMID]_24259288[PMID]_24259184[PMID]_24706016[PMID]_26545172[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_26545172[PMID]"}],"phenotypes":null}