{"orpha":300570,"name":"Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare, genetic, non-syndromic cerebral malformation due to abnormal neuronal migration disease characterized by the association of cortical dysplasia and pontocerebellar hypoplasia, manifesting with global developmental delay, mild to severe intellectual disability, axial hypotonia, strabismus, nystagmus and, occasionally, optic nerve hypoplasia. Brain imaging reveals variable malformations, including frontally predominant microgyria, gyral disorganization and simplification, dysmorphic and hypertrophic basal ganglia, cerebellar vermis dysplasia, brainstem/corpus callosum hypoplasia, and/or olfactory bulbs agenesis.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-300570/","orphanet_url":"https://www.orpha.net/en/disease/detail/300570","names":{"fr":{"name":"Dysgénésie corticale avec hypoplasie pontocérébelleuse due à une mutation TUBB3","definition":"Malformation cérébrale non syndromique rare d'origine génétique due à une anomalie de migration neuronale, caractérisée par l'association d'une dysplasie corticale et d'une hypoplasie pontocérébelleuse, se manifestant par un retard global de développement, une déficience intellectuelle légère à sévère, une hypotonie axiale, un strabisme, un nystagmus et, occasionnellement, une hypoplasie du nerf optique. L'imagerie cérébrale révèle des malformations variables, notamment une microgyrie à prédominance frontale, une désorganisation et une simplification gyrales, une dysmorphie et une hypertrophie des ganglions de la base, une dysplasie du vermis cérébelleux, une hypoplasie du tronc cérébral/corps calleux et/ou une agénésie des bulbes olfactifs."},"de":{"name":"Kortikale Dysgenese mit pontozerebellärer Hypoplasie durch TUBB3-Genmutation","definition":"Eine seltene, genetisch bedingte, nicht-syndromale zerebrale Fehlbildung aufgrund einer neuronalen Migrationsstörung, die durch die Assoziation von kortikaler Dysplasie und pontozerebellärer Hypoplasie gekennzeichnet ist und sich in einer globalen Entwicklungsverzögerung, leichter bis schwerer Intelligenzminderung, axialer Hypotonie, Strabismus, Nystagmus und gelegentlich Hypoplasie des Sehnervs manifestiert. Die Bildgebung des Gehirns zeigt unterschiedliche Fehlbildungen, einschließlich frontal vorherrschender Mikrogyrien, gyraler Desorganisation und Vereinfachung, dysmorpher und hypertropher Basalganglien, Dysplasie des Kleinhirns, Hypoplasie des Hirnstamms/Corpus callosum und/oder Agenesie des Riechkolbens."},"es":{"name":"Disgenesia cortical con hipoplasia pontocerebelosa por una mutación en el gen TUBB3","definition":"Es una malformación cerebral no sindrómica, de origen genético y poco frecuente, debida a una migración neuronal anómal. Se caracteriza por la asociación de displasia cortical e hipoplasia pontocerebelosa, que se manifiesta con retraso global del desarrollo, discapacidad intelectual de leve a grave, hipotonía axial, estrabismo, nistagmo y ocasionalmente hipoplasia del nervio óptico. La neuroimagen revela malformaciones variables, incluyendo microgiria de predominio frontal, desorganización y simplificación del patrón giral, dismorfia e hipertrofia de los ganglios basales, displasia del vermis cerebeloso, hipoplasia del tronco encefálico / cuerpo calloso y/o agenesia de los bulbos olfatorios."},"it":{"name":"Disgenesia corticale con ipoplasia pontocerebellare da mutazione in TUBB3","definition":"È una malformazione cerebrale non sindromica rara, di origine genetica, causata da anomalie della migrazione neuronale, caratterizzata da displasia corticale e ipoplasia pontocerebellare. Esordisce con ritardo dello sviluppo globale, disabilità intellettiva da lieve a grave, ipotonia assiale, strabismo, nistagmo e, occasionalmente, ipoplasia del nervo ottico. Le neuroimmagini evidenziano malformazioni variabili, che comprendono la microgiria prevalentemente frontale, la disorganizzazione e la semplificazione delle circonvoluzioni, i dismorfismi e l'ipertrofia dei gangli basali, la displasia del verme cerebellare, l'ipoplasia del tronco encefalico/corpo calloso, e/o l'agenesia dei bulbi olfattivi."},"nl":{"name":"Corticale dysgenesie met pontocerebellaire hypoplasie door TUBB3-mutatie","definition":"Een zeldzame, genetische, niet-syndromale cerebrale malformatie als gevolg van abnormale neuronale migratie die gekarakteriseerd wordt door de associatie van corticale dysplasie en pontocerebellaire hypoplasie, en die zich manifesteert met algehele ontwikkelingsachterstand, milde tot ernstige intellectuele beperking, axiale hypotonie, strabisme, nystagmus en, occasioneel, hypoplasie van de oogzenuw. Beeldvorming van de hersenen toont variabele malformaties, waaronder overwegend frontale microgyrie, desorganisatie en vereenvoudiging van gyri, dysmorfe en hypertrofische basale ganglia, dysplasie van de cerebellaire vermis, hypoplasie van hersenstam/hersenbalk, en/of agenesie van de bulbus olfactorius (reukkolf)."},"pt":{"name":"Disgenesia cortical com hipoplasia pontocerebelosa por mutação TUBB3"},"pl":{"name":"Dysgenezja kory z hipoplazją mostu i móżdżku z powodu mutacji TUBB3"},"cs":{"name":"Kortikální dysgeneze s pontocerebelární hypoplázií způsobená mutací v TUBB3 genu"},"uk":{"name":"Дисгенезія кори головного мозку з гіпоплазією мозочка, зумовлена мутацією TUBB3","definition":"A rare, genetic, non-syndromic cerebral malformation due to abnormal neuronal migration disease characterized by the association of cortical dysplasia and pontocerebellar hypoplasia, manifesting with global developmental delay, mild to severe intellectual disability, axial hypotonia, strabismus, nystagmus and, occasionally, optic nerve hypoplasia. Brain imaging reveals variable malformations, including frontally predominant microgyria, gyral disorganization and simplification, dysmorphic and hypertrophic basal ganglia, cerebellar vermis dysplasia, brainstem/corpus callosum hypoplasia, and/or olfactory bulbs agenesis."},"zh":{"name":"TUBB3基因变异所致皮质发育不全伴桥小脑发育不良","definition":"一种罕见的遗传性非综合征性大脑畸形，由异常神经元迁移引起，特征是皮质和桥小脑发育不良，表现为全面发育迟缓、轻度至重度智力障碍、轴向张力减退、斜视、眼球震颤，偶有视神经发育不良。脑成像可见各种畸形，包括额部小脑回、脑回结构紊乱和简单化、基底节畸形和肥大、小脑蚓部发育不良、脑干/胼胝体发育不良和/或嗅球发育不良。"},"tr":{"name":"TUBB3 mutasyonuna bağlı pontoserebellar hipoplazi ile seyreden kortikal disgenezi"}},"xrefs":[{"source":"OMIM","code":"614039","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q04.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0013541","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5191309","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"13032","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":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":163209,"name":"Non-syndromic cerebral malformation due to abnormal neuronal migration","classifications":[147,156,181]}],"children":[],"genes":[{"symbol":"TUBB3","name":"tubulin beta 3 class III","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20829227[PMID]","hgnc":"20772","ensembl":"ENSG00000258947","omim":"602661","loci":["16q24.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":12.0,"area":"Worldwide","status":"Validated","source":"20829227[PMID]"},{"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":"2019-02-07","source":"24860126[PMID]_26130693[PMID]_26739025[PMID]_26639658[PMID]_30016746[PMID]_28951247[PMID]_24932993[PMID]_27781032[PMID]_20074521[PMID]_20829227[PMID]","terms":[{"hpo":"HP:0001250","label":"Seizure","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000496","label":"Abnormality of eye movement","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002334","label":"Abnormality of the cerebellar vermis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001488","label":"Bilateral ptosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025336","label":"Delayed ability to sit","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010862","label":"Delayed fine motor development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002194","label":"Delayed gross motor development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000565","label":"Esotropia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002474","label":"Expressive language delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","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:0002540","label":"Inability to walk","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001339","label":"Lissencephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001338","label":"Partial agenesis of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002126","label":"Polymicrogyria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008897","label":"Postnatal growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011344","label":"Severe global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009879","label":"Simplified gyral pattern","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002497","label":"Spastic ataxia","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:0007260","label":"Type II lissencephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012332","label":"Abnormal autonomic nervous system physiology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002134","label":"Abnormal basal ganglia morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030534","label":"Abnormal best corrected visual acuity test","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000733","label":"Abnormal repetitive mannerisms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000570","label":"Abnormal saccadic eye movements","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010663","label":"Abnormality of thalamus morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030302","label":"Agenesis of the anterior commissure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008619","label":"Bilateral sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001320","label":"Cerebellar vermis hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001491","label":"Congenital fibrosis of extraocular muscles","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002967","label":"Cubitus valgus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012434","label":"Delayed social development","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025101","label":"Dysgenesis of the hippocampus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000712","label":"Emotional lability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005469","label":"Flat occiput","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007359","label":"Focal-onset seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002857","label":"Genu valgum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030903","label":"Grasp reflex","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0040326","label":"Hypoplasia of the olfactory bulb","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005216","label":"Impaired mastication","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100785","label":"Insomnia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002751","label":"Kyphoscoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007048","label":"Large basal ganglia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006956","label":"Lateral ventricle dilatation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000256","label":"Macrocephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001840","label":"Metatarsus adductus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002343","label":"Normal pressure hydrocephalus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000657","label":"Oculomotor apraxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000609","label":"Optic nerve hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001357","label":"Plagiocephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011451","label":"Primary microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012760","label":"Reduced social responsiveness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000736","label":"Short attention span","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001773","label":"Short foot","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012697","label":"Small basal ganglia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0200055","label":"Small hand","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001264","label":"Spastic diplegia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002510","label":"Spastic tetraplegia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002943","label":"Thoracic scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000473","label":"Torticollis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000572","label":"Visual loss","frequency":"Occasional (29-5%)","criteria":null}]}}