{"orpha":2478,"name":"Megalencephalic leukoencephalopathy with subcortical cysts","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["MLC","Megalencephalic leukodystrophy","Megalencephaly-cystic leukodystrophy syndrome","Vacuolating megalencephalic leukoencephalopathy with subcortical cysts","Van der Knaap syndrome"],"definition":"A form of leukodystrophy that is characterized by infantile-onset macrocephaly, often with mild neurologic signs at presentation (such as mild motor delay), which worsen with time, leading to poor ambulation, falls, ataxia, spasticity, increasing seizures and cognitive decline. Brain magnetic resonance imaging reveals diffusely abnormal and mildly swollen white matter as well as subcortical cysts in the anterior temporal and frontoparietal regions.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-2478/","orphanet_url":"https://www.orpha.net/en/disease/detail/2478","names":{"fr":{"name":"Leucoencéphalopathie mégalencéphalique avec kystes sous-corticaux","synonyms":["Leucodystrophie mégalencéphalique","MLC","Syndrome de Van der Knaap","Syndrome de leucoencéphalopathie mégalencéphalique-kystes subcorticaux","Syndrome de mégalencéphalie-leucodystrophie kystique"],"definition":"Forme de leucodystrophie caractérisée par une macrocéphalie infantile, souvent associée à des signes neurologiques légers à la présentation (tel qu'un retard moteur léger), qui s'aggravent avec le temps, conduisant à des troubles de la déambulation, des chutes, une ataxie, une spasticité, des convulsions progressives et un déclin cognitif. L'imagerie par résonance magnétique (IRM) du cerveau révèle des anomalies diffuses de la substance blanche avec un oedème léger, ainsi que des kystes sous-corticaux dans les régions frontopariétales et temporales antérieures."},"de":{"name":"Megalenzephale Leukoenzephalopathie mit subkortikalen Zysten","synonyms":["Leukodystrophie, megalenzephale","MLC","Megalenzephalie - zystische Leukodystrophie","Vakuolisierende Myelinonopathie mit subkortikalen Zysten","Van der Knaap-Syndrom"],"definition":"Eine Form der Leukodystrophie, die durch eine Makrozephalie im Kindesalter gekennzeichnet ist, häufig mit leichten neurologischen Symptomen bei der Erstuntersuchung (z. B. einer leichten motorischen Verzögerung), die sich mit der Zeit verschlimmern und zu Gehbehinderung, Stürzen, Ataxie, Spastik, zunehmender Anfallshäufigkeit und einer Abnahme der kognitiven Fähigkeiten führen. Die Magnetresonanztomographie des Gehirns zeigt eine diffuse, abnorme und leicht geschwollene weiße Substanz sowie subkortikale Zysten in den anterioren temporalen und frontoparietalen Regionen."},"es":{"name":"Leucoencefalopatía megalencefálica con quistes subcorticales","synonyms":["Leucodistrofia megalencefálica","Leucoencefalopatía megalencefálica vacuolizante con quistes subcorticales","MLC","Megalencefalia-leucodistrofia quística","Síndrome de Van der Knapp"],"definition":"Es una forma de leucodistrofia que se caracteriza por una macrocefalia de aparición en la infancia, a menudo con síntomas neurológicos leves a la presentación (tales como retraso motor leve), que empeoran con el tiempo, conduciendo a trastorno de la marcha, caídas, ataxia, espasticidad, convulsiones de frecuencia e intensidad crecientes y deterioro cognitivo. Las imágenes de resonancia magnética cerebrales muestran una afectación difusa y ligera inflamación de la sustancia blanca así como quistes subcorticales en las regiones temporal anterior y frontoparietal."},"it":{"name":"Leucoencefalopatia megalencefalica con cisti sottocorticali","synonyms":["Leucodistrofia megalencefalica","Leucoencefalopatia megalencefalica vacuolizzante con cisti sottocorticali","MLC","Megalencefalia - leucodistrofia cistica","Sindrome di Van der Knapp"],"definition":"La leucoencefalopatia megalencefalica con cisti sottocorticali (MLC) è una forma di leucodistrodia caratterizzata da macrocefalia ad esordio infantile, spesso con segni neurologici lievi all'esordio (lieve ritardo motorio), che peggiorano nel tempo, esitando in difficoltà alla deambulazione, cadute, atassia, spasticità, crisi epilettiche progressive e deterioramento cognitivo. La risonanza magnetica cerebrale evidenzia anomalie diffuse nella sostanza bianca, che appare lievemente gonfia, e cisti subcorticali nelle regioni temporale anteriore e fronto-parietale."},"nl":{"name":"Megalencefalische leuko-encefalopathie met subcorticale cysten","synonyms":["MLC","Megalencefalie - cystische leukodystrofie-syndroom","Megalencefalische leukodystrofie","Syndroom van Van der Knaap","Vacuoliserende megalencefalische leuko-encefalopathie met subcorticale cysten"],"definition":"Een vorm van leukodystrofie, gekenmerkt door infantiele aanvang van macrocefalie, vaak met milde neurologische verschijnselen bij manifestatie (zoals milde motorische achterstand) die mettertijd verergeren en leiden tot slecht stappen, vallen, ataxie, spasticiteit, toenemend aantal insulten en cognitieve aftakeling. Beeldvorming van hersenen met magnetische resonantie toont diffuse abnormale en mild gezwollen witte materie, alsook subcorticale cysten in voorste temporale en frontopariëtale gebieden."},"pt":{"name":"Leucoencefalopatia megalencefálica com quistos subcorticais","synonyms":["Leucoencefalopatia megalencefálica","MLC","Síndrome Van der Knaap","Síndrome de megalencefalia-leucodistrofia quística"]},"pl":{"name":"Leukoencefalopatia z wielkogłowiem o powolnym przebiegu","synonyms":["Leukodystrofia z wielkogłowiem","MLC","Wielkogłowie - leukodystrofia torbielowata","Wielkogłowie z leukodystrofią wakuolizującą i torbielami podkorowymi","Zespół Van der Knaapa"]},"cs":{"name":"Megaloencefalická leukoencefalopatie se subkortikálními cystami","synonyms":["MLC","Megaloencefalická leukodystrofie","Syndrom zahrnující megaloencefalii a cystickou leukodystrofii","Vakuolující megaloencefalická leukoencefalopatie se subkortikálními cystami","Van der Knaapové syndrom"]},"uk":{"name":"Мегаленцефалічна лейкоенцефалопатія з підкірковими кістами","synonyms":["Мегаленцефалічна лейкодистрофія","Синдром мегаленцефалічно-кістозної лейкодистрофії","MLC","Вакуолізуюча мегаленцефалічна лейкоенцефалопатія з підкірковими кістами","Синдром Ван дер Кнаапа"],"definition":"A form of leukodystrophy that is characterized by infantile-onset macrocephaly, often with mild neurologic signs at presentation (such as mild motor delay), which worsen with time, leading to poor ambulation, falls, ataxia, spasticity, increasing seizures and cognitive decline. Brain magnetic resonance imaging reveals diffusely abnormal and mildly swollen white matter as well as subcortical cysts in the anterior temporal and frontoparietal regions."},"zh":{"name":"巨脑白质病变伴皮下囊肿","synonyms":["空泡性巨脑白质脑病伴皮质下囊肿"]},"tr":{"name":"Subkortikal kistler ile seyreden megalensefalik lökoensefalopati","synonyms":["MLC","Van der Knaap sendromu","Megalensefalik lökodistrofi","Megalensefali-kistik lökodistrofi sendromu","Subkortikal kistler ile seyreden vakuolize megalensefalik lökoensefalopati"]}},"xrefs":[{"source":"OMIM","code":"604004","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"613925","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"613926","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620447","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620448","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E75.2","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"8A44.3","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"945878586"},{"source":"MONDO","code":"0011391","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C536141","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1858854","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"3445","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":68356,"name":"Leukodystrophy","classifications":[156,181]}],"children":[],"genes":[{"symbol":"AQP4","name":"aquaporin 4","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"37143309[PMID]","hgnc":"637","ensembl":"ENSG00000171885","omim":"600308","loci":["18q11.2"]},{"symbol":"GPRC5B","name":"G protein-coupled receptor class C group 5 member B","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"37143309[PMID]","hgnc":"13308","ensembl":"ENSG00000167191","omim":"605948","loci":["16p12.3"]},{"symbol":"HEPACAM","name":"hepatic and glial cell adhesion molecule","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301707[PMID]","hgnc":"26361","ensembl":"ENSG00000165478","omim":"611642","loci":["11q24.2"]},{"symbol":"MLC1","name":"modulator of VRAC current 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301707[PMID]","hgnc":"17082","ensembl":"ENSG00000100427","omim":"605908","loci":["22q13.33"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant","Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":100.0,"area":"Worldwide","status":"Validated","source":"21977097[PMID]_12189496[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":"2025-06-11","source":"20301707[PMID]_29079544[PMID]_38487253[PMID]_23079554[PMID]","terms":[{"hpo":"HP:0001251","label":"Ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:6000461","label":"Cerebral subcortical cyst","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007341","label":"Diffuse swelling of cerebral white matter","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001268","label":"Mental deterioration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002333","label":"Motor deterioration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005490","label":"Postnatal macrocephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002317","label":"Unsteady gait","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002071","label":"Abnormality of extrapyramidal motor function","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002305","label":"Athetosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000717","label":"Autism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012762","label":"Cerebral white matter atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002312","label":"Clumsiness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002133","label":"Status epilepticus","frequency":"Occasional (29-5%)","criteria":null}]}}