{"orpha":314679,"name":"Cerebrofacioarticular syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Van Maldergem syndrome"],"definition":"Cerebrofacioarticular syndrome is a rare multiple congenital anomalies syndrome characterized by mild to severe intellectual disability, a distinctive facial gestalt (blepharophimosis, maxillary hypoplasia, telecanthus, microtia and atresia of the external auditory meatus) as well as skeletal and articular abnormalities (e.g. camptodactyly of the fingers, cutaneous syndactyly, talipes equinovarus, flexion contractures of the proximal interphalangeal joints, hip or elbow subluxation, joint laxity). Affected individuals also present neonatal hypotonia, variable respiratory manifestations, chronic feeding difficulties and gray matter heterotopia.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-314679/","orphanet_url":"https://www.orpha.net/en/disease/detail/314679","names":{"fr":{"name":"Syndrome cérébrofacioarticulaire","synonyms":["Syndrome de Van Maldergem"],"definition":"Le syndrome cérébrofacioarticulaire est un syndrome rare d'anomalies congénitales multiples. Il se caractérise par un déficit intellectuel léger à sévère, une dysmorphie faciale caractéristique (blépharophimosis, hypoplasie maxillaire, télécanthus, microtie et atrésie du méat auditif externe), ainsi que des anomalies articulaires et squelettiques (camptodactylie au niveau de la main, syndactylie cutanée, pieds varus équins, contractures de flexion des articulations interphalangées proximales, subluxation du coude ou de la hanche, laxité articulaire). Les individus affectés présentent aussi une hypotonie néonatale, des manifestations respiratoires variables, des difficultés chroniques pour s'alimenter et une hétérotopie de la substance grise."},"de":{"name":"Zerebro-fazio-artikuläres Syndrom","synonyms":["Van Maldergem-Syndrom"],"definition":"Ein seltenes Syndrom mit multiplen kongenitalen Anomalien, das sich durch eine leichte bis schwere Intelligenzminderung, eine ausgeprägte Gesichtsform (Blepharophimose, Maxillahypoplasie, Telecanthus, Mikrotie und Atresie des äußeren Gehörgangs) sowie Skelett- und Gelenkanomalien (z. z. B. Kamptodaktylie der Finger, kutane Syndaktylie, Talipes equinovarus, Flexionskontrakturen der proximalen Interphalangealgelenke, Hüft- oder Ellenbogensubluxation, Gelenklaxität) manifestiert. Betroffene Personen zeigen auch neonatale Hypotonie, variable respiratorische Manifestationen, chronische Fütterungsschwierigkeiten und Heterotopie der grauen Substanz."},"es":{"name":"Síndrome cerebro-facio-articular","synonyms":["Síndrome de Van Maldergem"],"definition":"El síndrome cerebrofacioarticular es un síndrome de anomalías congénitas múltiples poco frecuente caracterizado por discapacidad intelectual de leve a grave, expresión facial característica (blefarofimosis, hipoplasia maxilar, telecantus, microtia y atresia del conducto auditivo externo), así como anomalías esqueléticas y articulares (p. ej., camptodactilia de los dedos, sindactilia cutánea, talipes equinovarus, contracturas por flexión de las articulaciones interfalángicas proximales, subluxación de cadera o codo, laxitud articular). Los individuos afectados también presentan hipotonía neonatal, manifestaciones respiratorias variables, dificultades alimentarias crónicas y heterotopia de la sustancia gris."},"it":{"name":"Sindrome cerebro-facio-articolare","synonyms":["Sindrome di Van Maldergem"],"definition":"La sindrome cerebro-facio-articolare è una malattia rara da anomalie congenite multiple, caratterizzata da disabilità intellettiva da lieve a grave, facies caratteristica (blefarofimosi, ipoplasia mascellare, telecanto, microtia e atresia del meato acustico esterno), anomalie scheletriche e articolari (camptodattilia delle dita delle mani, sindattilia cutanea, piede equino-varo, contratture delle articolazioni interfalangee prossimali durante la flessione, sublussazione dell'anca o del gomito, lassità articolare). Inoltre, i pazienti presentano ipotonia neonatale, sintomi respiratori variabili, difficoltà di alimentazione croniche ed eterotopia della sostanza grigia."},"nl":{"name":"Cerebrofacioarticulair syndroom","synonyms":["Syndroom van Van Maldergem"],"definition":"Cerebro-facio-articulair syndroom is een zeldzaam syndroom met meervoudige congenitale anomalieën en wordt gekarakteriseerd door milde tot ernstige intellectuele achterstand, een typische gelaatsvorm (blefarofimose, hypoplasie van het bovenkaakbeen, telecanthus, microtie en atresie van de uitwendige gehoorgang), alsook afwijkingen van het skelet en de gewrichten (e.g. camptodactylie van de vingers, cutane syndactylie, talipes equinovarus (klompvoet), flexiecontracturen van de proximale interfalangeale gewrichten, subluxatie van heup of elleboog, gewrichtslaxiteit). Getroffen individuen vertonen ook neonatale hypotonie, variabele respiratoire manifestaties, chronische voedingsproblemen en heterotopie van de grijze stof."},"pt":{"name":"Síndrome cerebro-facio-articular","synonyms":["Síndrome de Van Maldergem"]},"pl":{"name":"Zespół mózgowo-twarzowo-stawowy","synonyms":["Zespół Van Maldergema"]},"cs":{"name":"Cerebro-facio-artikulární syndrom","synonyms":["Van Maldergemův syndrom"]},"uk":{"name":"Цереброфаціоартікулярний синдром","synonyms":["Синдром Ван Мальдергема"],"definition":"Cerebrofacioarticular syndrome is a rare multiple congenital anomalies syndrome characterized by mild to severe intellectual disability, a distinctive facial gestalt (blepharophimosis, maxillary hypoplasia, telecanthus, microtia and atresia of the external auditory meatus) as well as skeletal and articular abnormalities (e.g. camptodactyly of the fingers, cutaneous syndactyly, talipes equinovarus, flexion contractures of the proximal interphalangeal joints, hip or elbow subluxation, joint laxity). Affected individuals also present neonatal hypotonia, variable respiratory manifestations, chronic feeding difficulties and gray matter heterotopia."},"zh":{"name":"脑筋膜关节综合征","synonyms":["Van Maldergem综合征"],"definition":"脑-面-关节综合征是一种罕见的多发性先天性畸形综合征，其特征为轻至重度智力残疾、独特的面部特征（睑裂狭小、上颌发育不全、内眦距过宽、小耳畸形和外耳道闭锁），也伴有骨骼和关节异常（如先天性指屈曲、皮肤并指畸形、马蹄内翻足、近端指间关节屈曲挛缩、髋关节或肘关节半脱位、关节松弛）。受累的个体还表现为新生儿肌张力减退，不同表现的呼吸症状，慢性喂养困难和灰质异位。"},"tr":{"name":"Serebrofasiyoartiküler sendrom","synonyms":["Van Maldergem sendromu"]}},"xrefs":[{"source":"OMIM","code":"601390","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"615546","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0017813","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C536530","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1832390","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"5456","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"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":"DCHS1","name":"dachsous cadherin-related 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24056717[PMID]","hgnc":"13681","ensembl":"ENSG00000166341","omim":"603057","loci":["11p15.4"]},{"symbol":"FAT4","name":"FAT atypical cadherin 4","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24056717[PMID]","hgnc":"23109","ensembl":"ENSG00000196159","omim":"612411","loci":["4q28.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":9.0,"area":"Worldwide","status":"Validated","source":"22473091[PMID]_24056717[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":"2019-10-11","source":"29681106[PMID]_22473091[PMID]","terms":[{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012385","label":"Camptodactyly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008551","label":"Microtia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002778","label":"Abnormal trachea morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000405","label":"Conductive hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011471","label":"Gastrostomy tube feeding in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002342","label":"Intellectual disability, moderate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000239","label":"Large fontanelles","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000938","label":"Osteopenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000089","label":"Renal hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001159","label":"Syndactyly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001627","label":"Abnormal heart morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008197","label":"Absence of pubertal development","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001274","label":"Agenesis of corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002025","label":"Anal stenosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001545","label":"Anteriorly placed anus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0200138","label":"Bilateral choanal atresia/stenosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000581","label":"Blepharophimosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002825","label":"Caudal appendage","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001320","label":"Cerebellar vermis hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006989","label":"Dysplastic corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002282","label":"Gray matter heterotopia","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:0000327","label":"Hypoplasia of the maxilla","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000047","label":"Hypospadias","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0040079","label":"Irregular dentition","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001004","label":"Lymphedema","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000160","label":"Narrow mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001642","label":"Pulmonic stenosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100716","label":"Self-injurious behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001762","label":"Talipes equinovarus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002779","label":"Tracheomalacia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Occasional (29-5%)","criteria":null}]}}