{"orpha":527497,"name":"NKX6-2-related autosomal recessive hypomyelinating leukodystrophy","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Autosomal recessive hypomyelinating leukodystrophy-progressive spastic ataxia","SPAX8"],"definition":"A rare leukodystrophy characterized by a spectrum of progressive neurologic manifestations comprising rapidly progressive early-onset nystagmus, spastic tetraplegia, and visual and hearing impairment, resulting in death in early childhood, as well as later onset of slowly progressive complex spastic ataxia with pyramidal and cerebellar symptoms and loss of developmental milestones. Brain imaging shows diffuse hypomyelination of the subcortical and deep white matter, cerebellar atrophy, and diffuse spinal cord volume loss.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-527497/","orphanet_url":"https://www.orpha.net/en/disease/detail/527497","names":{"fr":{"name":"Leucodystrophie hypomyélinisante autosomique récessive associée à NKX6-2","synonyms":["Leucodystrophie hypomyélinisante autosomique récessive-ataxie spastique progressive","SPAX8"],"definition":"Leucodystrophie rare caractérisée par un spectre de signes cliniques neurologiques progressifs incluant un nystagmus à début précoce rapidement progressif, une tétraplégie spastique et des déficiences visuelles et auditives, causant le décès dans la petite enfance, ainsi que l'apparition ultérieure d'une ataxie spastique complexe lentement progressive avec des atteintes du système pyramidal et cérébelleux et un retard du développement. L'IRM met en évidence une hypomyélinisation diffuse de la substance blanche sous-corticale et profonde, une atrophie cérébelleuse et une perte diffuse du volume de la moelle épinière."},"de":{"name":"NKX6-2-assoziierte autosomal-rezessive hypomyelinisierende Leukodystrophie","synonyms":["SPAX8"],"definition":"Eine seltene Leukodystrophie, die durch ein Spektrum progressiver neurologischer Manifestationen gekennzeichnet ist, darunter ein rasch progredienter, früh einsetzender Nystagmus, spastische Tetraplegie sowie Seh- und Hörstörungen, die im frühen Kindesalter zum Tod führen, sowie ein späteres Auftreten einer langsam progredienten komplexen spastischen Ataxie mit pyramidalen und zerebellären Symptomen und dem Verlust von Meilensteinen in der Entwicklung. Die Bildgebung des Gehirns zeigt eine diffuse Hypomyelinisierung der subkortikalen und tiefen weißen Substanz, Kleinhirnatrophie und einen diffusen Volumenverlust des Rückenmarks."},"es":{"name":"Leucodistrofia hipomielinizante autosómica recesiva asociada a NKX6-2","synonyms":["Leucodistrofia hipomielinizante autosómica recesiva-ataxia espástica progresiva","SPAX8"],"definition":"Es una leucodistrofia poco frecuente caracterizada por un espectro de manifestaciones neurológicas progresivas, que comprenden un inicio temprano rápidamente progresivo de nistagmo, tetraplejía espástica y afectación visual y auditiva, causando el fallecimiento en la infancia temprana. También es posible un inicio más tardío con una ataxia espástica compleja lentamente progresiva con síntomas piramidales y cerebelosos y pérdida de los hitos del desarrollo. La neuroimagen muestra una hipomielinización difusa de la sustancia blanca subcortical y profunda, atrofia cerebelosa y disminución global del volumen de la médula espinal."},"it":{"name":"Leucodistrofia ipomielinizzante autosomica recessiva correlata a NKX6-2","synonyms":["Leucodistrofia ipomielinizzante - atassia spastica progressiva autosomica recessiva","SPAX8"],"definition":"Si tratta di una leucodistrofia rara caratterizzata da una serie di sintomi neurologici progressivi (nistagmo ad esordio precoce e progressione rapida, tetraplegia spastica e deficit della vista e dell'udito) che esitano nella morte nella prima infanzia. Inoltre, i pazienti presentano un'atassia spastica complessa ad esordio più tardivo e a progressione lenta, sintomi piramidali e cerebellari e mancata acquisizione delle prime tappe dello sviluppo. Le neuroimmagini mostrano ipomielinizzazione diffusa della sostanza bianca subcorticale e profonda, atrofia cerebellare e perdita diffusa del volume del midollo spinale."},"nl":{"name":"NKX6-2-gerelateerde autosomaal recessieve hypomyeliniserende leukodystrofie","synonyms":["Autosomaal recessieve hypomyeliniserende leukodystrofie - progressieve spastische ataxie","SPAX8"],"definition":"Een zeldzame leukodystrofie, gekarakteriseerd door een spectrum van progressieve neurologische manifestaties, waaronder snel progressieve en vroeg optredende nystagmus, spastische tetraplegie, en visuele en auditieve stoornissen, met overlijden in de vroege kindertijd tot gevolg, alsook door latere aanvang van traag progressieve, complexe spastische ataxie met piramidale en cerebellaire symptomen, en verlies van ontwikkelingsmijlpalen. Beeldvorming van hersenen toont diffuse hypomyelinisatie van subcorticale en diepe witte stof, cerebellaire atrofie, en diffuus volumeverlies van ruggenmerg."},"pt":{"name":"Leucodistrofia hipomielinizante autossómica recessiva NKX6-2-relacionada"},"pl":{"name":"Autosomalna, recesywna leukodystrofia hipomielinizująca związana z NKX6-2","synonyms":["SPAX8","Autosomalna, recesywna leukodystrofia hipomielinizująca-postępująca ataksja/niezborność spastyczna"]},"cs":{"name":"NKX6-vázaná autozomálně recesivní hypomyelinizační leukodystrofie","synonyms":["SPAX8","Autozomálně recesivní hypomyelinizační leukodystrofie a progresivní spastická ataxie"]},"uk":{"name":"NKX6-2-повязана аутосомно-рецесивна гіпомієлінізуюча лейкодистрофія","synonyms":["Аутосомно-рецесивна гіпомієлінізуюча лейкодистрофія - прогресуюча спастична атаксія","SPAX8"],"definition":"A rare leukodystrophy characterized by a spectrum of progressive neurologic manifestations comprising rapidly progressive early-onset nystagmus, spastic tetraplegia, and visual and hearing impairment, resulting in death in early childhood, as well as later onset of slowly progressive complex spastic ataxia with pyramidal and cerebellar symptoms and loss of developmental milestones. Brain imaging shows diffuse hypomyelination of the subcortical and deep white matter, cerebellar atrophy, and diffuse spinal cord volume loss."},"zh":{"name":"NKX6-2基因相关的常染色体隐性低髓鞘化脑白质营养不良症","synonyms":["Autosomal recessive hypomyelinating leukodystrophy-progressive spastic ataxia","SPAX8"],"definition":"是一种罕见的脑白质营养不良症，其特征为一系列进行性神经系统表现，包括快速进行性早期眼球震颤、痉挛性四肢瘫痪、视觉和听觉障碍，导致幼儿期死亡，以及后期缓慢进行性复杂痉挛性共济失调，伴有锥体和小脑症状，发育不达标。脑影像学检查显示皮层下和深部白质弥漫性低髓鞘化，小脑萎缩，弥漫性脊髓体积缩小。"},"tr":{"name":"NKX6-2-ilişkili otozomal resesif hipomiyelinizan lökodistrofi","synonyms":["Otozomal çekinik hipomyelinizan lökodistrofi-ilerleyici spastik ataksi","SPAX8"]}},"xrefs":[{"source":"OMIM","code":"617560","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E75.2","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0033043","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4479653","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":316240,"name":"Autosomal recessive spastic ataxia","classifications":[156,181]},{"orpha":68356,"name":"Leukodystrophy","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"NKX6-2","name":"NK6 homeobox 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"28575651[PMID]","hgnc":"19321","ensembl":"ENSG00000148826","omim":"605955","loci":["10q26.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Childhood","Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":25.0,"area":"Worldwide","status":"Validated","source":"29388673[PMID]_30285346[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_29388673[PMID]_30285346[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-03-27","source":"29388673[PMID]_30285346[PMID]","terms":[{"hpo":"HP:0007256","label":"Abnormal pyramidal sign","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000571","label":"Hypometric saccades","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003429","label":"CNS hypomyelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002599","label":"Head titubation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030890","label":"Hyperintensity of cerebral white matter on MRI","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002415","label":"Leukodystrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007704","label":"Paroxysmal involuntary eye movements","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002191","label":"Progressive spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001007","label":"Hirsutism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0012534","label":"Dysesthesia","frequency":"Excluded (0%)","criteria":null}]}}