{"orpha":3447,"name":"Weaver syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["EZH2-related overgrowth syndrome"],"definition":"A rare PRC-2 complex-related overgrowth spectrum disorder characterized by pre- and post-natal overgrowth, facial dysmorphism (including hypertelorism, large fleshy ears and retrognathia with the appearance of a 'stuck-on' chin with associated horizontal skin crease) that is easily recognizable in early childhood. Majority of the patients present with mild intellectual disability. Additional variable features include macrocephaly, joint laxity, scoliosis, pectus excavatum, hypo- and/or hypertonia, poor coordination, soft dough skin, clinodactyly, camptodactyly of the fingers and/or toes, umbilical hernia, and a low hoarse cry in infancy. Many clinical features, including facial dysmorphism, attenuate with age. Patients may also have a higher risk of neuroblastoma.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-3447/","orphanet_url":"https://www.orpha.net/en/disease/detail/3447","names":{"fr":{"name":"Syndrome de Weaver","synonyms":["Syndrome d'hypercroissance associé à EZH2"],"definition":"Maladie rare du spectre de l'hypercroissance liée à complexe PRC-2 caractérisée par une croissance excessive prénatale et postnatale, ainsi que par une dysmorphie faciale (notamment un hypertélorisme, de grandes oreilles charnues et une rétrognathie avec un menton qui semble «&nbsp;bloqué&nbsp;» associé à un pli cutané horizontal) facilement reconnaissable dès la petite enfance. La majorité des patients présentent une déficience intellectuelle légère. Parmi les autres caractéristiques variables on observe une macrocéphalie, une laxité articulaire, une scoliose, un pectus excavatum, une hypo- et/ou l'hypertonie, une mauvaise coordination, une peau douce d'aspect pâteux, une clinodactylie, une camptodactylie des doigts et/ou des orteils, une hernie ombilicale et des pleurs rauques de faible intensité pendant la petite enfance. De nombreux traits cliniques, notamment la dysmorphie faciale, s'atténuent avec l'âge. Les patients peuvent également présenter un risque accru de développer un neuroblastome."},"de":{"name":"Weaver-Syndrom","synonyms":["EZH2-assoziiertes Großwuchssyndrom"],"definition":"Das Weaver-Syndrom (WVS) ist eine seltene, multisystemische Erkrankung, die sich durch eine hohe Statur, ein charakteristischen Erscheinungsbild im Gesicht (Hypertelorismus, Retrognathie) und eine variable geistige Behinderung auszeichnet. Weitere Symptome sind Kamptodaktylie, rauhe und tiefe Stimme, Muskelhypertonie, Nabel- und Leistenhernie und überschüssige, schlaffe Haut."},"es":{"name":"Síndrome de Weaver","synonyms":["Síndrome de sobrecrecimiento asociado a EZH2"],"definition":"Es un trastorno poco frecuente del espectro de sobrecrecimiento relacionado con el complejo PRC-2 que se caracteriza por sobrecrecimiento pre- y postnatal, dismorfia facial (incluyendo hipertelorismo, orejas grandes y carnosas y retrognatia con apariencia de mentón \"adherido\" con pliegue cutáneo horizontal asociado) fácilmente reconocible en la primera infancia. La mayoría de los pacientes presenta discapacidad intelectual leve. Entre las características variables adicionales se incluyen macrocefalia, laxitud articular, escoliosis, pectus excavatum, hipo- e/o hipertonía, mala coordinación, piel suave, clinodactilia, camptodactilia de los dedos de las manos y/o de los pies, hernia umbilical, y llanto ronco y grave en el lactante. Muchos rasgos clínicos, como la dismorfia facial, se atenúan con la edad. Los pacientes también pueden presentar un mayor riesgo de desarrollar neuroblastoma."},"it":{"name":"Sindrome di Weaver","synonyms":["Camptodattilia - iperaccrescimento - dismorfismi","Sindrome da iperaccrescimento correlata a EZH2"],"definition":"La sindrome di Weaver (WVS) è una malattia multisistemica rara, caratterizzata da alta statura, facies caratteristica (ipertelorismo, retrognazia) e disabilità cognitiva variabile, associati a camptodattilia, cute flaccida e soffice, ernia ombelicale e pianto debole e rauco."},"nl":{"name":"Syndroom van Weaver","synonyms":["EZH2-gerelateerd overgroeisyndroom"],"definition":"Een zeldzame PRC-2 complex-gerelateerde overgroei-spectrumstoornis, gekenmerkt door pre- en postnatale overgroei, en faciale dysmorfie (met onder meer hypertelorisme, grote oorlellen en retrognathie met het uiterlijk van een opgezette kin met geassocieerde horizontale huidplooi) die makkelijk herkenbaar is in de vroege kindertijd. De meerderheid van de patiënten vertoont milde intellectuele achterstand. Bijkomende variabele kenmerken zijn onder meer macrocefalie, gewrichtslaxiteit, scoliose, pectus excavatum (trechterborst), hypo- en/of hypertonie, ondermaatse coördinatie, zachte deegachtige huid, clinodactylie, camptodactylie van vingers en/of tenen, navelbreuk, en een laag hees gehuil in de zuigelingentijd. Vele klinische kenmerken, waaronder faciale dysmorfie, verzachten met het ouder worden. Patiënten lopen mogelijk ook een hoger risico op neuroblastoom."},"pt":{"name":"Síndrome Weaver","synonyms":["Síndrome de sobrecrescimento EZH2-relacionada","Síndrome de sobrecrescimento associado a EZH2"],"definition":"A síndrome Weaver (SW) é uma doença rara e multissistémica caracterizada por estatura alta, aspeto facial típico (hipertelorismo, retrognatia) e perturbação do desenvolvimento intelectual variável. As características adicionais podem incluir camptodactilia, pele macia e pastosa, hérnia umbilical e choro baixo e rouco."},"pl":{"name":"Zespół Weavera","synonyms":["Kamptodaktylia - przerost - nietypowa twarz"],"definition":"Zespół Weavera (Weaver syndrome-WVS) to rzadka, wieloukładowa choroba charakteryzująca się wyskim wzrostem, typowym wyglądem twarzy (hiperteloryzm, retrognacja) i zmienną niepełnosprawnością intelektualna. Dodatkowe objawy mogą obejmować kamptodaktylię, miękką, ciastowatą skórę, przepuklinę pępkową oraz niski, chrapliwy głos."},"cs":{"name":"Weaverův syndrom","synonyms":["Syndrom zahrnující kamptodaktylii, makrosomii a faciální dysmorfismus"]},"uk":{"name":"Синдром Вівера","synonyms":["Синдром надмірного росту, повязаний з EZH2","Синдром гіпертрофії, асоційований з EZH2"],"definition":"Weaver syndrome (WVS) is a rare, multisystem disorder characterized by tall stature, a typical facial appearance (hypertelorism, retrognathia) and variable intellectual disability. Additional features may include camptodactyly, soft doughy skin, umbilical hernia, and a low hoarse cry."},"zh":{"name":"Weaver综合征","synonyms":["指弯曲畸形-生长过度-特殊面容综合征"]},"tr":{"name":"Weaver sendromu","synonyms":["Kamptodaktili-aşırı büyüme-alışılmadık yüz sendromu"]}},"xrefs":[{"source":"OMIM","code":"277590","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.3","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"LD2C","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"2042913723"},{"source":"MONDO","code":"0010193","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C536687","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0265210","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"7878","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10083271","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":659387,"name":"PRC-2 complex-related overgrowth spectrum","classifications":[147,156,181,199]}],"children":[],"genes":[{"symbol":"NSD1","name":"nuclear receptor binding SET domain protein 1","gene_type":"gene with protein product","association":"Candidate gene tested in","status":"Not yet assessed","source":null,"hgnc":"14234","ensembl":"ENSG00000165671","omim":"606681","loci":["5q35.3"]},{"symbol":"SUZ12","name":"SUZ12 polycomb repressive complex 2 subunit","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"28229514[PMID]","hgnc":"17101","ensembl":"ENSG00000178691","omim":"606245","loci":["17q11.2"]},{"symbol":"EZH2","name":"enhancer of zeste 2 polycomb repressive complex 2 subunit","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22177091[PMID]_23865096[PMID]_24214728[PMID]","hgnc":"3527","ensembl":"ENSG00000106462","omim":"601573","loci":["7q36.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant","Not applicable"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":48.0,"area":"Worldwide","status":"Validated","source":"24214728[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_24214728[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0001231","label":"Abnormal fingernail morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000944","label":"Abnormal metaphysis morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010300","label":"Abnormally low-pitched voice","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0005616","label":"Accelerated skeletal maturation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000337","label":"Broad forehead","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001814","label":"Deep-set nails","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001609","label":"Hoarse voice","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001800","label":"Hypoplastic toenails","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000256","label":"Macrocephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000400","label":"Macrotia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001582","label":"Redundant skin","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000278","label":"Retrognathia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000098","label":"Tall stature","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001816","label":"Thin nail","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001769","label":"Broad foot","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011304","label":"Broad thumb","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100490","label":"Camptodactyly of finger","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002002","label":"Deep philtrum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002213","label":"Fine hair","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000023","label":"Inguinal hernia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001387","label":"Joint stiffness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001176","label":"Large hands","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000311","label":"Round face","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030680","label":"Abnormal cardiovascular system morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006101","label":"Finger syndactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008736","label":"Hypoplasia of penis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001761","label":"Pes cavus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001852","label":"Sandal gap","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001762","label":"Talipes equinovarus","frequency":"Occasional (29-5%)","criteria":null}]}}