{"orpha":496641,"name":"Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare, severe early-onset neurodegenerative encephalopathy characterized mainly by developmental delay (DD) / developmental regression (DR), epilepsy, cortical atrophy, secondary hypomyelination and thin corpus callosum. Additional features include secondary microcephaly, hypotonia, spasticity, optic atrophy and skeletal anomalies.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-496641/","orphanet_url":"https://www.orpha.net/en/disease/detail/496641","names":{"fr":{"name":"Syndrome d'atrophie cérébrale diffuse précoce-microcéphalie-faiblesse musculaire-atrophie optique","definition":"Encéphalopathie neurodégénérative rare sévère à début précoce, principalement caractérisée par un retard de développement/une régression du développement, une épilepsie, une atrophie corticale, une hypomyélinisation secondaire et un corps calleux mince. Les autres signes sont une microcéphalie secondaire, une hypotonie, une spasticité, une atrophie optique et des anomalies squelettiques."},"de":{"name":"Früh beginnende progressive diffuse Gehirnatrophie-Mikrozephalie-Muskelschwäche-Optikusatrophie-Syndrom","definition":"Eine früh einsetzende schwere neurodegenerative Enzephalopathie, die vor allem durch Entwicklungsverzögerung (DD) / Entwicklungsregression (DR), Epilepsie, kortikale Atrophie, sekundäre Hypomyelinisierung und dünnes Corpus callosum gekennzeichnet ist. Weitere Merkmale sind sekundäre Mikrozephalie, Hypotonie, Spastizität, Optikusatrophie und Skelettanomalien."},"es":{"name":"Síndrome de atrofia cerebral difusa progresiva de inicio precoz-microcefalia-debilidad muscular-atrofia óptica","definition":"Es una encefalopatía neurodegenerativa grave y poco frecuente de aparición temprana caracterizada principalmente por retraso/regresión del desarrollo, epilepsia, atrofia cortical, hipomielinización secundaria y adelgazamiento del cuerpo calloso. Otras características adicionales son microcefalia secundaria, hipotonía, espasticidad, atrofia óptica y anomalías esqueléticas."},"it":{"name":"Sindrome atrofia cerebrale diffusa progressiva ad esordio precoce-microcefalia-debolezza muscolare-atrofia ottica","definition":"Si tratta di una malattia neurodegenerativa grave e rara ad esordio precoce, caratterizzata da ritardo/regressione dello sviluppo, epilessia, atrofia corticale, ipomielinizzazione secondaria e corpo calloso sottile. I pazienti possono presentare anche microcefalia secondaria, ipotonia, spasticità, atrofia ottica e anomalie scheletriche."},"nl":{"name":"Progressieve diffuse hersenatrofie met vroege aanvang - microcefalie - spierzwakte - opticusatrofie-syndroom","definition":"Een zeldzame, ernstige, vroeg optredende neurodegeneratieve encefalopathie, hoofdzakelijk gekenmerkt door ontwikkelingsachterstand/ontwikkelingsregressie, epilepsie, corticale atrofie, secundaire hypomyelinisatie en dun corpus callosum. Bijkomende kenmerken zijn onder meer secundaire microcefalie, hypotonie, spasticiteit, opticusatrofie, en skeletanomalieën."},"pt":{"name":"Síndrome de atrofia cerebral difusa progressiva de início precoce-microcefalia-fraqueza muscular-atrofia óptica"},"pl":{"name":"Zespół wczesnej i postępującej rozsianej atrofii mózgu, osłabienia mięśniowego i zaniku nerwu wzrokowego"},"cs":{"name":"Syndrom zahrnující progresivní difuzní atrofii mozku s časným nástupem, mikrocefalii, svalovou slabost a atrofii optiků"},"uk":{"name":"Синдром ранньої прогресуючої дифузної атрофії головного мозку-мікроцефалії-мязової слабкості-атрофії зорового нерва","definition":"A rare, severe early-onset neurodegenerative encephalopathy characterized mainly by developmental delay (DD) / developmental regression (DR), epilepsy, cortical atrophy, secondary hypomyelination and thin corpus callosum. Additional features include secondary microcephaly, hypotonia, spasticity, optic atrophy and skeletal anomalies."},"zh":{"name":"早发型进行性弥漫性脑萎缩-小头肌-肌无力-视神经萎缩综合征","definition":"是一种罕见的遗传性神经退行性疾病，其特点是早期发病的弥散性脑萎缩、生长不足，伴有出生后小脑萎缩、发育迟缓、退行、深度智力障碍、肌张力低下、肌无力和萎缩、顽固性癫痫发作、痉挛和视神经萎缩。患者通常不能活动，常需机械通气。脑影像学显示脑和小脑萎缩、肌力减退、胼胝体变薄。"},"tr":{"name":"Erken başlangıçlı ilerleyici yaygın beyin atrofisi-mikrosefali-kas güçsüzlüğü-optik atrofi sendromu"}},"xrefs":[{"source":"OMIM","code":"617193","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G93.4","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0044646","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5567454","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":183500,"name":"Genetic neurodegenerative disease","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":182070,"name":"Rare neurodegenerative disease","classifications":[181]},{"orpha":441434,"name":"Syndromic hereditary optic neuropathy","classifications":[156,189]}],"children":[],"genes":[{"symbol":"TBCD","name":"tubulin folding cofactor D","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"27807845[PMID]_27666374[PMID]_27666370[PMID]","hgnc":"11581","ensembl":"ENSG00000141556","omim":"604649","loci":["17q25.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":39.0,"area":"Worldwide","status":"Validated","source":"27807845[PMID]_27666374[PMID]_27666370[PMID]_27928163[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_27807845[PMID]_27666374[PMID]_27666370[PMID]_27928163[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-07-11","source":"27807845[PMID]_27666370[PMID]_27666374[PMID]","terms":[{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003202","label":"Skeletal muscle atrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007179","label":"Absent smooth pursuit","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002069","label":"Bilateral tonic-clonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006808","label":"Cerebral hypomyelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010818","label":"Generalized tonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002187","label":"Intellectual disability, profound","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002191","label":"Progressive spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005484","label":"Secondary microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002445","label":"Tetraplegia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001284","label":"Areflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002804","label":"Arthrogryposis multiplex congenita","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012450","label":"Chronic constipation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003236","label":"Elevated circulating creatine kinase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002380","label":"Fasciculations","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003084","label":"Fractures of the long bones","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002342","label":"Intellectual disability, moderate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001357","label":"Plagiocephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001561","label":"Polyhydramnios","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011451","label":"Primary microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004887","label":"Respiratory failure requiring assisted ventilation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0045075","label":"Sparse eyebrow","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000020","label":"Urinary incontinence","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000687","label":"Widely spaced teeth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000733","label":"Abnormal repetitive mannerisms","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002607","label":"Bowel incontinence","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002524","label":"Cataplexy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001374","label":"Congenital hip dislocation","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002373","label":"Febrile seizure (within the age range of 3 months to 6 years)","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001007","label":"Hirsutism","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000400","label":"Macrotia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0007002","label":"Motor axonal neuropathy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000011","label":"Neurogenic bladder","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000768","label":"Pectus carinatum","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000767","label":"Pectus excavatum","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0006532","label":"Recurrent pneumonia","frequency":"Very rare (<4-1%)","criteria":null}]}}