{"orpha":3240,"name":"Early-onset progressive leukoencephalopathy-central nervous system calcification-deafness-visual impairment syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Early onset progressive leukoencephalopathy- central nervous system calcification- hearing loss-visual impairment syndrome"],"definition":"A rare genetic neurological disorder characterized by early-onset progressive leukoencephalopathy, severe developmental delay, early-onset or congenital deafness (only few cases reported without hearing loss), and visual impairment. All patients manifest calcifications in brain and spinal cord. Cognitive impairment, seizures, hypotonia, spastic tetraplegia or quadriplegia are observed in the majority of the patients. Variable features may include microcephaly and anemia.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-3240/","orphanet_url":"https://www.orpha.net/en/disease/detail/3240","names":{"fr":{"name":"Syndrome de leucoencéphalopathie progressive à début précoce-calcifications du système nerveux central-surdité-cécité","synonyms":["Syndrome de leucoencéphalopathie progressive à début précoce-calcification du système nerveux central-perte auditive-cécité"],"definition":"Maladie neurologique génétique rare caractérisée par une leucoencéphalopathie progressive à début précoce, un retard de développement sévère, une surdité à début précoce ou congénitale (seuls quelques cas sans perte auditive ont été rapportés) et une déficience visuelle. Tous les patients présentent des calcifications du cerveau et de la moelle épinière. Des troubles cognitifs, des crises d'épilepsie, une hypotonie, une tétraplégie ou une quadriplégie spastique sont observés chez la majorité des patients. La microcéphalie et l'anémie font partie des caractéristiques inconstantes."},"de":{"name":"Früh einsetzende progrediente Leukoenzephalopathie-ZNS-Kalzifikation-Schwerhörigkeit-Sehstörung-Syndrom","synonyms":["Syndrom der früh einsetzenden progredienten Leukoenzephalopathie mit ZNS-Verkalkung, Schwerhörigkeit und Sehbeeinträchtigung"],"definition":"Eine seltene genetisch bedingte neurologische Störung, die durch eine früh einsetzende progressive Leukoenzephalopathie, eine schwere Entwicklungsverzögerung, eine früh einsetzende oder angeborene Taubheit (nur wenige Fälle wurden ohne Hörverlust berichtet) und eine Sehbehinderung gekennzeichnet ist. Alle Patienten weisen Verkalkungen im Gehirn und Rückenmark auf. Kognitive Beeinträchtigungen, Krampfanfälle, Hypotonie, spastische Tetraplegie oder Quadriplegie werden bei der Mehrheit der Patienten beobachtet. Zu den variablen Merkmalen können Mikrozephalie und Anämie gehören."},"es":{"name":"Síndrome de leucoencefalopatía progresiva de inicio precoz-calcificación del sistema nervioso central-sordera-deficiencia visual","synonyms":["Síndrome de leucoencefalopatía progresiva de inicio precoz-calcificación del sistema nervioso central-hipoacusia-deficiencia visual"],"definition":"Es un trastorno neurológico genético poco frecuente caracterizado por leucoencefalopatía progresiva de aparición precoz, retraso grave del desarrollo, sordera congénita o de inicio temprano (sólo se han notificado unos pocos casos sin pérdida auditiva) y discapacidad visual. Todos los pacientes manifiestan calcificaciones en el cerebro y la médula espinal. En la mayoría de los pacientes se observa deterioro cognitivo, crisis epilépticas, hipotonía, tetraplejía espástica o cuadriplejía. Las características variables pueden incluir microcefalia y anemia."},"it":{"name":"Sindrome leucoencefalopatia progressiva ad esordio precoce-calcificazioni del sistema nervoso centrale- sordità-deficit visivo","synonyms":["Sindrome leucoencefalopatia progressiva ad esordio precoce-calcificazioni del sistema nervoso centrale-perdita dell'udito-deficit visivo"],"definition":"Si tratta di una malattia neurologica genetica rara sindromica, che esordisce nella prima infanzia con calcificazione progressiva del cervello e del midollo spinale, ritardo della crescita, deterioramento psicomotorio, sordità, anemia microcitica ipocromica e acidosi tubulare renale distale di grado variabile. Non sono stati descritti nuovi casi dopo il 1997."},"nl":{"name":"Vroeg optredende progressieve leuko-encefalopathie - calcificatie van centraal zenuwstelsel - doofheid - visuele stoornis-syndroom","synonyms":["Vroeg optredende progressieve leuko-encefalopathie - calcificatie van centraal zenuwstelsel - gehoorverlies - visuele stoornis-syndroom"],"definition":"Een zeldzame, genetische neurologische aandoening, gekenmerkt door vroeg optredende progressieve leuko-encefalopathie, ernstige ontwikkelingsachterstand, vroeg optredende of congenitale doofheid (slechts enkele gevallen zonder gehoorverlies werden gerapporteerd), en verlies van gezichtsvermogen. Alle patiënten vertonen verkalkingen in hersenen en ruggenmerg. Bij de meerderheid van de patiënten worden cognitieve functiestoornis, insulten, hypotonie, spastische tetraplegie of quadriplegie waargenomen. Mogelijke variabele kenmerken zijn onder meer microcefalie en anemie."},"pt":{"name":"Síndrome de leucoencefalopatia progressiva de início precoce-calcificação do sistema nervoso central-surdez-deficiência visual","synonyms":["Síndrome de leucoencefalopatia progressiva de início precoce-calcificação do sistema nervoso central-perda auditiva-deficiência visual"],"definition":"Doença neurológica genética rara caracterizada por leucoencefalopatia progressiva de início precoce, atraso grave no desenvolvimento, surdez de início precoce ou congénita (apenas alguns casos relatados sem perda auditiva) e deficiência visual. Todos os doentes evidenciam calcificações cerebrais e medulares. Compromisso cognitivo, convulsões, hipotonia, tetraplegia espástica ou tetraplegia são observados na maioria dos doentes. Características variáveis &#8203;&#8203;podem incluir microcefalia e anemia."},"pl":{"name":"Zwapnienia centralnego układu nerwowego - głuchota - kwasica kanalikowa - niedokrwistość","synonyms":["Zespół Yoshimura i Takeshita","Zespół zwapnienia ośrodkowego układu nerwowego-głuchoty-kwasicy cewkowej-niedokrwistości","Zespół postępującej leukoencefalopatii – zwapnienia ośrodkowego układu nerwowego – głuchoty – zaburzenia widzenia o wczesnym początku"],"definition":"Rzadkie, genetycznie uwarunkowane schorzenie neurologiczne charakteryzujące się postępującą leukoencefalopatią o wczesnym początku, ciężkim opóźnieniem rozwoju, głuchotą wrodzoną lub o wczesnym początku (zgłoszono tylko kilka przypadków bez utraty słuchu) i upośledzeniem wzroku. U wszystkich pacjentów występują zwapnienia w mózgu i rdzeniu kręgowym. U większości chorych obserwuje się upośledzenie funkcji poznawczych, drgawki, hipotonię, spastyczny niedowład lub porażenie czterokończynowe. Zmienne cechy mogą obejmować małogłowie lub niedokrwistość."},"cs":{"name":"Syndrom zahrnující kalcifikaci centrálního nervového systému, hluchotu, tubulární acidózu a anémii","synonyms":["Yoshimurův-Takeshitův syndrom","Yoshimura-Takeshitův syndrom"]},"uk":{"name":"Синдром ранньої прогресуючої лейкоенцефалопатії - кальцифікації центральної нервової системи-глухоти-порушення зору","synonyms":["Синдром ранньої прогресуючої лейкоенцефалопатії - кальцифікації центральної нервової системи - втрати слуху - порушення зору"],"definition":"A rare genetic neurological disorder characterized by early-onset progressive leukoencephalopathy, severe developmental delay, early-onset or congenital deafness (only few cases reported without hearing loss), and visual impairment. All patients manifest calcifications in brain and spinal cord. Cognitive impairment, seizures, hypotonia, spastic tetraplegia or quadriplegia are observed in the majority of the patients. Variable features may include microcephaly and anemia."},"zh":{"name":"中枢神经系统钙化-耳聋-肾小管酸中毒-贫血综合征","synonyms":["Yoshimura-Takeshita综合征"]},"tr":{"name":"Merkezi sinir sistemi kireçlenmesi-sağırlık-tübüler asidoz-anemi sendromu","synonyms":["Merkezi sinir sistemi kireçlenmesi-işitme kaybı-tübüler asidoz-anemi sendromu","Yoshimura-Takeshita sendromu"]}},"xrefs":[{"source":"OMIM","code":"619147","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G93.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD2H.Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"2051416590"},{"source":"MONDO","code":"0017924","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5925004","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":696870,"name":"Common variable immunodeficiency phenotype due to germinal monogenic mutation","classifications":[156,195]},{"orpha":314822,"name":"Primary renal tubular acidosis","classifications":[156,188]},{"orpha":90642,"name":"Rare syndromic genetic deafness","classifications":[147,156,200]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"KARS1","name":"lysyl-tRNA synthetase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"28887846[PMID]","hgnc":"6215","ensembl":"ENSG00000065427","omim":"601421","loci":["16q23.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["No data available"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":2.0,"area":"Worldwide","status":"Validated","source":"9112970[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_9112970[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-03-22","source":"9112970[PMID]","terms":[{"hpo":"HP:0004463","label":"Absent brainstem auditory responses","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001047","label":"Atopic dermatitis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002506","label":"Diffuse cerebral atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002171","label":"Gliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002599","label":"Head titubation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004840","label":"Hypochromic microcytic anemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003281","label":"Increased circulating ferritin concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002510","label":"Spastic tetraplegia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007346","label":"Subcortical white matter calcifications","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008568","label":"Vestibular areflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002014","label":"Diarrhea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001873","label":"Thrombocytopenia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Excluded (0%)","criteria":null},{"hpo":"HP:0011002","label":"Osteopetrosis","frequency":"Excluded (0%)","criteria":null}]}}