{"orpha":171680,"name":"Lissencephaly due to TUBA1A mutation","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"Lissencephaly (LIS) due to TUBA1A mutation is a congenital cortical development anomaly due to abnormal neuronal migration involving neocortical and hippocampal lamination, corpus callosum, cerebellum and brainstem. A large clinical spectrum can be observed, from children with severe epilepsy and intellectual and motor deficit to cases with severe cerebral dysgenesis in the antenatal period leading to pregnancy termination due to the severity of the prognosis.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-171680/","orphanet_url":"https://www.orpha.net/en/disease/detail/171680","names":{"fr":{"name":"Lissencéphalie due à une mutation de TUBA1","definition":"La lissencéphalie due à une mutation de <i>TUBA1A</i> est une anomalie congénitale du développement cortical due à une migration neuronale anormale impliquant la lamination néocorticale et de l'hippocampe, le corps calleux, le cervelet et le tronc cérébral. La maladie présente un large spectre clinique, allant d'une épilepsie sévère et des troubles moteurs et intellectuels chez l'enfant, aux cas présentant une dysgénésie cérébrale sévère au cours de la période anténatale, conduisant à une interruption médicale de la grossesse du fait de la sévérité du pronostic."},"de":{"name":"Lissenzephalie durch TUBA1A-Genmutation","definition":"Die Lissenzephalie (LIS) durch TUBA1A-Mutation ist eine angeborene Entwicklungsstörung der Hirnrinde mit abnormer neuronaler Migration in den Schichten des Neokortex und Hippocampus, im Corpus callosum, Zerebellum und im Hirnstamm. Das klinische Spektrum ist weit und reicht von Kindern mit schwerer Epilepsie und intellektuellem und motorischen Defizit bis zu Fällen mit schwerer Dysgenesie des Gehirns in der vorgeburtlichen Periode, die wegen der Schwere der Prognose einen Abbruch der Schwangerschaft nahelegt."},"es":{"name":"Lisencefalia por una mutación en el gen TUBA1A","definition":"La lisencefalia (LIS) por mutaciones en TUBA1A es una anomalía congénita del desarrollo cortical causada por una migración neuronal anómala que afecta a la laminación neocortical y del hipocampo, el cuerpo calloso, el cerebelo y el tallo cerebral. Puede observarse un amplio espectro clínico, desde niños con epilepsia grave y déficit intelectual y motor, a casos con disgenesia cerebral grave en el periodo prenatal que conduce a una interrupción del embarazo por la gravedad del pronóstico."},"it":{"name":"Lissencefalia da mutazioni di TUBA1A","definition":"La lissencefalia (LIS) da mutazione di TUBA1A è un'anomalia congenita dello sviluppo corticale da migrazione neuronale anomala, che interessa la laminazione neocorticale e dell'ippocampo, il corpo calloso, il cervelletto e il tronco cerebrale. Può associarsi a quadri clinici molto variabili, che comprendono l'epilessia grave nei bambini, il deficit motorio e cognitivo, la disgenesia cerebrale grave neonatale, che può giustificare l'interruzione della gravidanza a causa della prognosi infausta."},"nl":{"name":"Lissencefalie door TUBA1A-mutatie","definition":"Een congenitale anomalie van corticale ontwikkeling, te wijten aan abnormale migratie van neuronen in lagen van neocortex en hippocampus, corpus callosum, cerebellum, en hersenstam. Er wordt een breed klinisch spectrum waargenomen, gaande van kinderen met ernstige epilepsie en intellectuele en motorische functiestoornissen, tot gevallen met ernstige cerebrale dysgenesie in de prenatale periode resulterend in beëindiging van de zwangerschap vanwege de ernst van de prognose."},"pt":{"name":"Lisencefalia por mutação no gene TUBA1A"},"pl":{"name":"Lizencefalia z powodu mutacji TUBA1A"},"cs":{"name":"Lisencefalie způsobená mutací TUBA1A genu"},"uk":{"name":"Лісенцефалія внаслідок мутації TUBA1A","definition":"Lissencephaly (LIS) due to TUBA1A mutation is a congenital cortical development anomaly due to abnormal neuronal migration involving neocortical and hippocampal lamination, corpus callosum, cerebellum and brainstem. A large clinical spectrum can be observed, from children with severe epilepsy and intellectual and motor deficit to cases with severe cerebral dysgenesis in the antenatal period leading to pregnancy termination due to the severity of the prognosis."},"zh":{"name":"TUBA1A基因突变无脑畸形","definition":"TUBA1A基因突变所致无脑回畸形（LIS）是一种先天性皮质发育异常，由于新皮质、海马、胼胝体、小脑和脑干的神经元异常移行所致。临床表现多样，可表现为严重癫痫伴智力和运动障碍，也可表现为胎儿脑发育不良，因预后较差而停止妊娠。"},"tr":{"name":"TUBA1A mutasyonuna bağlı lizensefali"}},"xrefs":[{"source":"OMIM","code":"611603","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q04.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD20.1","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1006889224"},{"source":"MONDO","code":"0012703","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4305153","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":48471,"name":"Lissencephaly","classifications":[147,156,181]}],"children":[],"genes":[{"symbol":"TUBA1A","name":"tubulin alpha 1a","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"18669490[PMID]_18954413[PMID]_22264709[PMID]","hgnc":"20766","ensembl":"ENSG00000167552","omim":"602529","loci":["12q13.12"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant","Not applicable"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":15.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"},{"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":"2022-09-15","source":"30744660[PMID]_17584854[PMID]_23528852[PMID]","terms":[{"hpo":"HP:0025102","label":"Dysgenesis of the basal ganglia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001274","label":"Agenesis of corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002069","label":"Bilateral tonic-clonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001320","label":"Cerebellar vermis hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002198","label":"Dilated fourth ventricle","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025101","label":"Dysgenesis of the hippocampus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002365","label":"Hypoplasia of the brainstem","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034051","label":"Hypoplastic anterior limbs of the internal capsule","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001339","label":"Lissencephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000308","label":"Microretrognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031882","label":"Agyria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006989","label":"Dysplastic corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007359","label":"Focal-onset seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025517","label":"Hypoplastic hippocampus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012469","label":"Infantile spasms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000609","label":"Optic nerve hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001302","label":"Pachygyria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001338","label":"Partial agenesis of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012650","label":"Perisylvian polymicrogyria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002126","label":"Polymicrogyria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002251","label":"Aganglionic megacolon","frequency":"Very rare (<4-1%)","criteria":null}]}}