{"orpha":391376,"name":"Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Asparagine synthetase deficiency"],"definition":"A rare, genetic, neurometabolic disorder characterized by severe, progressive microcephaly, severe to profound global development delay, intellectual disability, seizures (typically tonic and/or myoclonic and frequently intractable), hyperekplexia, and axial hypotonia with appendicular spasticity, as well as hyperreflexia, dyskinetic quadriplegia, and abnormal brain morphology (cerebral atrophy with variable additional features including ventriculomeglay, pons and/or cerebellar hypoplasia, simplified gyral pattern and delayed myelination). Cortical blindness, feeding difficulties and respiratory insufficiency may also be associated.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-391376/","orphanet_url":"https://www.orpha.net/en/disease/detail/391376","names":{"fr":{"name":"Syndrome de microcéphalie congénitale-encéphalopathie sévère-atrophie cérébrale progressive","synonyms":["Déficit en asparagine synthétase"],"definition":"Maladie neurométabolique rare d'origine génétique caractérisée par une microcéphalie sévère et progressive, un retard de développement global sévère à profond, une déficience intellectuelle, des crises convulsives (généralement toniques et/ou myocloniques et souvent réfractaires), une hyperexplexie, une hypotonie axiale avec spasticité appendiculaire, une hyperréflexie, une quadriplégie dyskinétique et une morphologie cérébrale anormale (atrophie cérébrale associée à d'autres caractéristiques inconstantes, à savoir ventriculomégalie, hypoplasie pontique et/ou cérébelleuse, schéma simplifié des gyri et retard de myélinisation). Une cécité corticale, des difficultés à s'alimenter et une insuffisance respiratoire peuvent également être associées."},"de":{"name":"Kongenitale Mikrozephalie-schwere Enzephalopathie-progressive zerebrale Atrophie-Syndrom","synonyms":["Asparagin-Synthetase-Mangel"]},"es":{"name":"Síndrome de microcefalia congénita-encefalopatía grave-atrofia cerebral progresiva","synonyms":["Deficiencia de asparagina sintetasa"],"definition":"El síndrome de microcefalia congénita - encefalopatía grave - atrofia cerebral progresiva es un trastorno neurometabólico, genético y poco frecuente, caracterizado por microcefalia grave progresiva, retraso global del desarrollo de grave a profundo, discapacidad intelectual, convulsiones (generalmente tónicas y/o mioclónicas y con frecuencia intratables), hiperekplexia e hipotonía axial con espasticidad apendicular, así como hiperreflexia, tetraplejia discinética y anomalía morfologíca cerebral (atrofia cerebral con características adicionales variables que incluyen ventriculomegalia, hipoplasia pontina y/o cerebelosa, patrón giral simplificado y mielinización retardada). También pueden asociarse ceguera cortical, dificultades de alimentación e insuficiencia respiratoria."},"it":{"name":"Sindrome da microcefalia congenita, encefalopatia grave e atrofia cerebrale progressiva","synonyms":["Deficit dell'asparagina sintentasi"],"definition":"La sindrome che associa la microcefalia congenita, l'encefalopatia grave e l'atrofia cerebrale progressiva è una malattia neurometabolica genetica rara, caratterizzata da microcefalia progressiva grave, ritardo dello sviluppo globale grave-profondo, disabilità intellettiva, crisi epilettiche (di solito toniche e/o miocloniche; spesso non trattabili), iperecplessia, ipotonia assiale con spasticità appendicolare, iperreflessia, quadriplegia discinetica e anomalie morfologiche del cervello (atrofia cerebrale associata ad altre anomalie variabili, che comprendono la ventricolomegalia, l'ipoplasia del ponte e/o del cervelletto, la semplificazione delle circonvoluzioni e il ritardo della mielinizzazione). Può associarsi a cecità corticale, difficoltà di alimentazione ed insufficienza respiratoria."},"nl":{"name":"Congenitale microcefalie - ernstige encefalopathie - progressieve cerebrale atrofie-syndroom","synonyms":["Asparaginesynthetasedeficiëntie"],"definition":"Congenitale microcefalie - ernstige encefalopathie - progressieve cerebrale atrofie-syndroom is een zeldzame, genetische, neurometabole stoornis die gekarakteriseerd wordt door ernstige, progressieve microcefalie, ernstige tot totale algehele ontwikkelingsachterstand, intellectuele achterstand, insulten (doorgaans tonisch en/of myoclonisch en frequent onbehandelbaar), hyperekplexie, en axiale hypotonie met appendiculaire spasticiteit, alsook hyperreflexie, dyskinetische quadriplegie, en abnormale morfologie van de hersenen (cerebrale atrofie met variabele bijkomende kenmerken waaronder ventriculomegalie, hypoplasie van de pons en/of het cerebellum, vereenvoudigd gyraal patroon en vertraagde myelinisatie). Corticale blindheid, voedingsproblemen en respiratoire insufficiëntie kunnen ook geassocieerd zijn."},"pt":{"name":"Síndrome de microcefalia congénita-encefalopatia grave-atrofia cerebral progressiva"},"pl":{"name":"Zespół wrodzone małogłowie-ciężka encefalopatia- postępujący zanik mózgu","synonyms":["Niedobór syntetazy kwasu asparaginianowego"]},"cs":{"name":"Syndrom zahrnující vrozenou mikrocefalii, těžkou encefalopatii a progresivní mozkovou atrofii","synonyms":["Deficit asparagin syntetázy"]},"uk":{"name":"Синдром вродженої мікроцефалії-тяжкої енцефалопатії-прогресуючої церебральної атрофії","synonyms":["Дефіцит аспарагінсинтетази"],"definition":"A rare, genetic, neurometabolic disorder characterized by severe, progressive microcephaly, severe to profound global development delay, intellectual disability, seizures (typically tonic and/or myoclonic and frequently intractable), hyperekplexia, and axial hypotonia with appendicular spasticity, as well as hyperreflexia, dyskinetic quadriplegia, and abnormal brain morphology (cerebral atrophy with variable additional features including ventriculomeglay, pons and/or cerebellar hypoplasia, simplified gyral pattern and delayed myelination). Cortical blindness, feeding difficulties and respiratory insufficiency may also be associated."},"zh":{"name":"先天性小头畸形-重度脑病-进行性脑萎缩综合征","synonyms":["天冬酰胺合成酶缺乏症"],"definition":"先天性小头畸形-严重脑病-进行性脑萎缩综合征是一种罕见的遗传性神经代谢紊乱，其特征是严重的进行性小头畸形，重至极重度的全面发育迟缓、智力障碍、癫痫发作(典型的强直性和/或肌阵挛，经常难以治愈)、功能亢进、轴性低张力伴附件痉挛、反射亢进、运动性四肢瘫痪和脑形态异常(脑萎缩伴有多种其他特征，包括脑室扩大，桥脑和/或小脑发育不全，脑回简化和髓鞘形成延迟)。皮质盲、喂养困难和呼吸功能不全也可能与本病有关。"},"tr":{"name":"Doğumsal mikrosefali-ağır ensefalopati-ilerleyici serebral atrofi sendromu","synonyms":["Asparagin sentetaz eksikliği"]}},"xrefs":[{"source":"OMIM","code":"615574","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E72.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C50.Y","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0014258","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C3809971","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":391381,"name":"Disorder of asparagine metabolism","classifications":[150,156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]}],"children":[],"genes":[{"symbol":"ASNS","name":"asparagine synthetase (glutamine-hydrolyzing)","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"24139043[PMID]","hgnc":"753","ensembl":"ENSG00000070669","omim":"108370","loci":["7q21.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":20.0,"area":"Worldwide","status":"Validated","source":"28776279[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_28776279[PMID]"}],"phenotypes":null}