{"orpha":505237,"name":"Early-onset seizures-distal limb anomalies-facial dysmorphism-global developmental delay syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by variable developmental delay, intellectual disability, early-onset seizures, and facial dysmorphism (including arched eyebrows, long palpebral fissures, prominent nasal bridge, large ears, thin upper lip, and high arched palate). Other reported features are microcephaly, hypotonia, growth retardation, congenital heart defects, and malformations of the fingers and toes, as well as additional neurologic manifestations (such as ataxia or spastic quadriplegia). Brain imaging may show hypoplastic corpus callosum, white matter abnormalities, or cortical atrophy.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-505237/","orphanet_url":"https://www.orpha.net/en/disease/detail/505237","names":{"fr":{"name":"Syndrome d'épilepsie à début précoce-anomalies des membres distaux-dysmorphie faciale-retard global de développement","definition":"Anomalies congénitales multiples/syndrome dysmorphique rare caractérisé par un retard de développement variable, une déficience intellectuelle, des crises convulsives à apparition précoce et une dysmorphie faciale (sourcils arqués, longues fentes palpébrales, une arête nasale proéminente, de grandes oreilles, une lèvre supérieure fine et un palais ogival). Les autres signes cliniques rapportés sont la microcéphalie, l'hypotonie, le retard de croissance, les malformations cardiaques congénitales et les malformations des doigts et des orteils, ainsi que des signes cliniques neurologiques supplémentaires (tels que l'ataxie ou la quadriplégie spastique). L'IRM peut révéler un corps calleux hypoplasique, des anomalies de la substance blanche ou une atrophie corticale."},"de":{"name":"Früh beginnende Krampfanfälle-distale Gliedmaßenanomalien-Gesichtsdysmorphien-allgemeine Entwicklungsverzögerung-Syndrom","definition":"Ein seltenes genetisch bedingtes Syndrom mit multiplen kongenitalen Anomalien/Dysmorphien, das durch variable Entwicklungsverzögerungen, Intelligenzminderung, früh einsetzende Krampfanfälle und Gesichtsdysmorphien (einschließlich gewölbter Augenbrauen, langer Lidspalten, hervorstehender Nasenrücken, großer Ohren, dünner Oberlippe und hochgewölbtem Gaumen) gekennzeichnet ist. Außerdem werden Mikrozephalie, Hypotonie, Wachstumsverzögerung, angeborene Herzfehler und Fehlbildungen der Finger und Zehen sowie zusätzliche neurologische Manifestationen (wie Ataxie oder spastische Tetraplegie) berichtet. Die Bildgebung des Gehirns kann ein hypoplastisches Corpus Callosum, Anomalien der weißen Substanz oder eine kortikale Atrophie zeigen."},"es":{"name":"Síndrome de crisis de inicio precoz-anomalías de las extremidades distales-dismorfia facial-retraso generalizado del desarrollo","definition":"Es un síndrome dismórfico/ de múltiples anomalías congénitas de base genética y poco frecuente caracterizado por un retraso variable del desarrollo psicomotor, discapacidad intelectual, crisis de inicio precoz y dismorfia facial (incluyendo cejas arqueadas, fisuras palpebrales amplias, puente nasal prominente, orejas grandes, labio superior fino y paladar ojival). Otras características descritas son microcefalia, hipotonía, retraso del crecimiento, defectos cardíacos congénitos y malformaciones de los dedos de manos y pies, así como manifestaciones neurológicas adicionales (como ataxia o cuadriplejía espástica). La neuroimagen puede mostrar hipoplasia del cuerpo calloso, anomalías de la sustancia blanca o atrofia cortical."},"it":{"name":"Sindrome crisi epilettiche ad esordio precoce-anomalie della parte distale degli arti- dismorfismi facciali-ritardo dello sviluppo globale","definition":"Si tratta di una malattia genetica rara da anomalie/dismorfismi congeniti multipli, caratterizzata da ritardo dello sviluppo di gravità variabile, disabilità intellettiva, crisi epilettiche ad esordio precoce e dismorfismi facciali (sopracciglia arcuate, rime palpebrali lunghe, sella nasale prominente, orecchie grandi, labbro superiore sottile e palato ogivale). Altri segni clinici sono la microcefalia, l'ipotonia, il ritardo della crescita, le cardiopatie congenite, le malformazioni delle dita delle mani e dei piedi, e i sintomi neurologici (atassia o quadriplegia spastica). Le neuroimmagini mostrano una ipoplasia del corpo calloso, anomalie della sostanza bianca o una atrofia corticale."},"nl":{"name":"Vroeg aanvangende insulten - distale ledemaatanomalieën - faciale dysmorfie - globale ontwikkelingsachterstand-syndroom","definition":"Een zeldzaam, genetisch syndroom met multipele congenitale anomalieën/dysmorfie, gekarakteriseerd door variabele ontwikkelingsachterstand, intellectuele achterstand, vroeg aanvangende insulten, en faciale dysmorfie (met onder meer gebogen wenkbrauwen, lange ooglidspleten, prominente neusbrug, grote oren, dunne bovenlip, en hoog gebogen verhemelte). Andere kenmerken die werden gerapporteerd, zijn onder meer microcefalie, hypotonie, groeiretardatie, congenitale hartdefecten, en malformaties van vingers en tenen, alsook bijkomende neurologische manifestaties (zoals ataxie of spastische quadriplegie). Beeldvorming van hersenen toont mogelijk hypoplastisch corpus callosum, afwijkingen van witte stof, of corticale atrofie."},"pt":{"name":"Síndrome de convulsões-anomalias distais dos membros-dismorfia facial-atraso do desenvolvimento de início precoce"},"pl":{"name":"Zespół napadów padaczkowych o wczesnym początku, wad dystalnych odcinków kończyn, dysmorfii twarzy i całościowego zaburzenia rozwoju"},"cs":{"name":"Syndrom zahrnující záchvaty s časným nástupem, anomálie distální části končetin, faciální dysmorfismus a celkové opoždění vývoje"},"uk":{"name":"Синдром раннього початку судом-дистальних аномалій кінцівок- дизморфізму обличчя-глобальної затримки розвитку","definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by variable developmental delay, intellectual disability, early-onset seizures, and facial dysmorphism (including arched eyebrows, long palpebral fissures, prominent nasal bridge, large ears, thin upper lip, and high arched palate). Other reported features are microcephaly, hypotonia, growth retardation, congenital heart defects, and malformations of the fingers and toes, as well as additional neurologic manifestations (such as ataxia or spastic quadriplegia). Brain imaging may show hypoplastic corpus callosum, white matter abnormalities, or cortical atrophy."},"zh":{"name":"早期癫痫发作-远端肢体异常-面部畸形-全身性发育迟缓综合症"},"tr":{"name":"Erken başlangıçlı nöbetler-distal ekstremite anomalileri-fasiyal dismorfizm-yaygın gelişme geriliği sendromu"}},"xrefs":[{"source":"OMIM","code":"617452","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0044319","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5568770","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":166472,"name":"Monogenic disease with epilepsy","classifications":[156,181]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]}],"children":[],"genes":[{"symbol":"OTUD6B","name":"OTU deubiquitinase 6B","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"28343629[PMID]","hgnc":"24281","ensembl":"ENSG00000155100","omim":"612021","loci":["8q21.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":12.0,"area":"Worldwide","status":"Validated","source":"28343629[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_28343629[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-02-25","source":"28343629[PMID]","terms":[{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Very frequent (99-80%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very frequent (99-80%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007370","label":"Aplasia/Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000248","label":"Brachycephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011304","label":"Broad thumb","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004325","label":"Decreased body weight","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005469","label":"Flat occiput","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002553","label":"Highly arched eyebrow","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001187","label":"Hyperextensibility of the finger joints","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003121","label":"Limb joint contracture","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000527","label":"Long eyelashes","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000276","label":"Long face","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000637","label":"Long palpebral fissure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000400","label":"Macrotia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001845","label":"Overlapping toe","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000426","label":"Prominent nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000278","label":"Retrognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000960","label":"Sacral dimple","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001762","label":"Talipes equinovarus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001182","label":"Tapered finger","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000219","label":"Thin upper lip vermilion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000445","label":"Wide nose","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008772","label":"Aplasia/Hypoplasia of the external ear","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001166","label":"Arachnodactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001631","label":"Atrial septal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000729","label":"Autistic behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012450","label":"Chronic constipation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002510","label":"Spastic tetraplegia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001770","label":"Toe syndactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001629","label":"Ventricular septal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100021","label":"Cerebral palsy","frequency":"Very rare (<4-1%)","criteria":null}]}}