{"orpha":544503,"name":"RNF13-related severe early-onset epileptic encephalopathy","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["RNF13-related severe EOEE"],"definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by congenital microcephaly, infantile-onset epileptic encephalopathy, and profound developmental delay. Additional reported features include cortical visual impairment, sensorineural hearing loss, increased muscle tone, limb contractures, scoliosis, and dysmorphic features like midface hypoplasia, narrow forehead, short nose, narrowed nasal bridge, and small chin. Brain imaging may show thin corpus callosum and delayed myelination.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-544503/","orphanet_url":"https://www.orpha.net/en/disease/detail/544503","names":{"fr":{"name":"Encéphalopathie épileptique sévère à début précoce associée à RNF13","definition":"Anomalies congénitales multiples/syndrome dysmorphique rare d'origine génétique caractérisé par une microcéphalie congénitale, une encéphalopathie épileptique à début infantile et un retard profond de développement. Parmi les autres caractéristiques rapportées figurent : déficience visuelle corticale, surdité neurosensorielle, augmentation du tonus musculaire, contractures des membres, scoliose et dysmorphie à type d'hypoplasie de l'étage moyen du visage, de front étroit, de nez court, de pont nasal étroit et de petit menton. Un corps calleux fin et un retard de myélinisation peuvent s'observer à l'imagerie cérébrale."},"de":{"name":"Enzephalopathie, epileptische, frühinfantile, RNF13-assoziierte","synonyms":["RNF13-assoziierte schwere EOEE"],"definition":"Ein genetisch bedingtes Dysmorphie-Syndrom mit multiplen Anomalien, das durch kongenitale Mikrozephalie, epileptische Enzephalopathie im Kindesalter und tiefgreifende Entwicklungsverzögerung gekennzeichnet ist. Zu den weiteren berichteten Merkmalen gehören kortikale Sehstörungen, sensorineurale Schwerhörigkeit, erhöhter Muskeltonus, Kontrakturen der Gliedmaßen, Skoliose und faziale Dysmorphien wie Mittelgesichtshypoplasie, schmale Stirn, kurze Nase, schmaler Nasenrücken und kleines Kinn. Die Bildgebung des Gehirns kann ein dünnes Corpus Callosum und eine verzögerte Myelinisierung zeigen."},"es":{"name":"Encefalopatía epiléptica grave de inicio precoz asociada al gen RNF13","synonyms":["EOEE grave asociada al gen RNF13"],"definition":"Es un síndrome dismórfico / con múltiples anomalías congénitas genético y poco frecuente caracterizado por microcefalia congénita, encefalopatía epiléptica de inicio en la lactancia y retraso profundo del desarrollo. Las características adicionales descritas incluyen afectación visual cortical, pérdida auditiva neurosensorial, aumento del tono muscular, contracturas de las extremidades, escoliosis y características dismórficas como hipoplasia del tercio medio facial, frente estrecha, nariz corta, puente nasal estrecho y mentón pequeño. Las imágenes cerebrales pueden mostrar adelgazamiento del cuerpo calloso y retraso de la mielinización."},"it":{"name":"Encefalopatia epilettica grave ad esordio precoce correlata a RNF13","definition":"Si tratta di una malattia genetica rara da anomalie/dismorfismi congeniti multipli, caratterizzata da microcefalia congenita, encefalopatia epilettica ad esordio infantile e grave ritardo dello sviluppo. Altri segni clinici comprendono la compromissione corticale della vista, la sordità neurosensoriale, l'aumento del tono muscolare, le contratture degli arti, la scoliosi e i dismorfismi facciali (ipoplasia medio-facciale, fronte stretta, naso corto, sella nasale stretta e mento piccolo). Le neuroimmagini rivelano un assottigliamento del corpo calloso e ritardo della mielinizzazione."},"nl":{"name":"RNF13-gerelateerde ernstige epileptische encefalopathie met vroege aanvang","synonyms":["RNF13-gerelateerde EOEE"],"definition":"Een zeldzaam, genetisch meervoudige congenitale anomalieën/dysmorfie-syndroom, gekarakteriseerd door congenitale microcefalie, infantiel aanvangende epileptische encefalopathie, en zeer ernstige ontwikkelingsachterstand. Bijkomende kenmerken die reeds werden gerapporteerd, zijn onder meer corticale visuele stoornis, sensorineuraal gehoorverlies, verhoogde spiertonus, contracturen van ledematen, scoliose, en dysmorfe kenmerken zoals hypoplasie van middengezicht, smal voorhoofd, korte neus, smalle neusbrug, en kleine kin. Beeldvorming van hersenen toont mogelijk dun corpus callosum en vertraagde myelinisatie."},"pt":{"name":"Encefalopatia epilética grave de início precoce RNF13-relacionada"},"pl":{"name":"Ciężka wczesna encefalopatia padaczkowa związana z RNF13","synonyms":["RNF13-related severe EOEE"]},"cs":{"name":"RNF13-vázaná závažná epileptická encefalopatie s časným nástupem","synonyms":["RNF13-vázaná závažná EOEE"]},"uk":{"name":"Важка рання епілептична енцефалопатія, повязана з RNF13","synonyms":["Тяжка ЕОЕЕ, повязана з RNF13"],"definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by congenital microcephaly, infantile-onset epileptic encephalopathy, and profound developmental delay. Additional reported features include cortical visual impairment, sensorineural hearing loss, increased muscle tone, limb contractures, scoliosis, and dysmorphic features like midface hypoplasia, narrow forehead, short nose, narrowed nasal bridge, and small chin. Brain imaging may show thin corpus callosum and delayed myelination."},"zh":{"name":"RNF13基因相关严重早发型癫痫性脑病","synonyms":["RNF13-related severe EOEE"],"definition":"一种罕见的遗传性多发性先天性异常/畸形综合征，其特点是先天性小头畸形、婴儿期癫痫性脑病和显著发育迟缓。其他报道的特征包括皮质视觉障碍、感音神经性听力损失、肌张力增高、四肢挛缩、脊柱侧弯，以及畸形特征，如中面部发育不良、前额狭窄、短鼻、鼻梁狭窄和小颏。脑影像学检查可能显示胼胝体薄，髓鞘形成迟缓。"},"tr":{"name":"RNF13 -ilişkili ağır erken başlangıçlı epileptik ensefalopati","synonyms":["RNF13-ilişkili ağır EOEE"]}},"xrefs":[{"source":"OMIM","code":"618379","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G40.4","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0034106","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5193065","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]},{"orpha":90642,"name":"Rare syndromic genetic deafness","classifications":[147,156,200]}],"children":[],"genes":[{"symbol":"RNF13","name":"ring finger protein 13","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (gain of function) in","status":"Assessed","source":"30595371[PMID]","hgnc":"10057","ensembl":"ENSG00000082996","omim":"609247","loci":["3q25.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":3.0,"area":"Worldwide","status":"Validated","source":"30595371[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_30595371[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-06-16","source":"30595371[PMID]","terms":[{"hpo":"HP:0000496","label":"Abnormality of eye movement","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100704","label":"Cerebral visual impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011185","label":"EEG with focal epileptiform discharges","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010845","label":"EEG with generalized slow activity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0200134","label":"Epileptic encephalopathy","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:0001371","label":"Flexion contracture","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011471","label":"Gastrostomy tube feeding in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000023","label":"Inguinal hernia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002187","label":"Intellectual disability, profound","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025373","label":"Interictal EEG abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000737","label":"Irritability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011800","label":"Midface retrusion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000341","label":"Narrow forehead","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000446","label":"Narrow nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000711","label":"Restlessness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000331","label":"Short chin","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003196","label":"Short nose","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025405","label":"Visual fixation instability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0040126","label":"Abnormal vitamin B12 level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002069","label":"Bilateral tonic-clonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002750","label":"Delayed skeletal maturation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012098","label":"Edema of the dorsum of feet","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007514","label":"Edema of the dorsum of hands","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011432","label":"Elevated maternal circulating alpha-fetoprotein concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006094","label":"Finger joint hypermobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001385","label":"Hip dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005072","label":"Hyperextensibility at wrists","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000668","label":"Hypodontia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012469","label":"Infantile spasms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006070","label":"Metacarpophalangeal joint contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002164","label":"Nail dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002098","label":"Respiratory distress","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100806","label":"Sepsis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001182","label":"Tapered finger","frequency":"Occasional (29-5%)","criteria":null}]}}