ORPHA:2478
Megalencephalic leukoencephalopathy with subcortical cysts
Synonyms: MLC · Megalencephalic leukodystrophy · Megalencephaly-cystic leukodystrophy syndrome · Vacuolating megalencephalic leukoencephalopathy with subcortical cysts · Van der Knaap syndrome
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal dominant, Autosomal recessive
- Age of onset
- Infancy, Neonatal
- Status
- active
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.
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Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Megalencephalic leukoencephalopathy with subcortical cysts | MLC · Megalencephalic leukodystrophy · Megalencephaly-cystic leukodystrophy syndrome · Vacuolating megalencephalic leukoencephalopathy with subcortical cysts · Van der Knaap syndrome |
| fr | Leucoencéphalopathie mégalencéphalique avec kystes sous-corticaux | Leucodystrophie mégalencéphalique · MLC · Syndrome de Van der Knaap · Syndrome de leucoencéphalopathie mégalencéphalique-kystes subcorticaux · Syndrome de mégalencéphalie-leucodystrophie kystique |
| de | Megalenzephale Leukoenzephalopathie mit subkortikalen Zysten | Leukodystrophie, megalenzephale · MLC · Megalenzephalie - zystische Leukodystrophie · Vakuolisierende Myelinonopathie mit subkortikalen Zysten · Van der Knaap-Syndrom |
| es | Leucoencefalopatía megalencefálica con quistes subcorticales | Leucodistrofia megalencefálica · Leucoencefalopatía megalencefálica vacuolizante con quistes subcorticales · MLC · Megalencefalia-leucodistrofia quística · Síndrome de Van der Knapp |
| it | Leucoencefalopatia megalencefalica con cisti sottocorticali | Leucodistrofia megalencefalica · Leucoencefalopatia megalencefalica vacuolizzante con cisti sottocorticali · MLC · Megalencefalia - leucodistrofia cistica · Sindrome di Van der Knapp |
| nl | Megalencefalische leuko-encefalopathie met subcorticale cysten | MLC · Megalencefalie - cystische leukodystrofie-syndroom · Megalencefalische leukodystrofie · Syndroom van Van der Knaap · Vacuoliserende megalencefalische leuko-encefalopathie met subcorticale cysten |
| pt | Leucoencefalopatia megalencefálica com quistos subcorticais | Leucoencefalopatia megalencefálica · MLC · Síndrome Van der Knaap · Síndrome de megalencefalia-leucodistrofia quística |
| pl | Leukoencefalopatia z wielkogłowiem o powolnym przebiegu | Leukodystrofia z wielkogłowiem · MLC · Wielkogłowie - leukodystrofia torbielowata · Wielkogłowie z leukodystrofią wakuolizującą i torbielami podkorowymi · Zespół Van der Knaapa |
| cs | Megaloencefalická leukoencefalopatie se subkortikálními cystami | MLC · Megaloencefalická leukodystrofie · Syndrom zahrnující megaloencefalii a cystickou leukodystrofii · Vakuolující megaloencefalická leukoencefalopatie se subkortikálními cystami · Van der Knaapové syndrom |
| uk | Мегаленцефалічна лейкоенцефалопатія з підкірковими кістами | Мегаленцефалічна лейкодистрофія · Синдром мегаленцефалічно-кістозної лейкодистрофії · MLC · Вакуолізуюча мегаленцефалічна лейкоенцефалопатія з підкірковими кістами · Синдром Ван дер Кнаапа |
| zh | 巨脑白质病变伴皮下囊肿 | 空泡性巨脑白质脑病伴皮质下囊肿 |
| tr | Subkortikal kistler ile seyreden megalensefalik lökoensefalopati | MLC · Van der Knaap sendromu · Megalensefalik lökodistrofi · Megalensefali-kistik lökodistrofi sendromu · Subkortikal kistler ile seyreden vakuolize megalensefalik lökoensefalopati |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 604004 | E | validated | |
| OMIM | 613925 | BTNT | validated | |
| OMIM | 613926 | BTNT | validated | |
| OMIM | 620447 | BTNT | validated | |
| OMIM | 620448 | BTNT | validated | |
| ICD-10 | E75.2 | NTBT | attributed | validated |
| ICD-11 | 8A44.3 | NTBT | index | validated |
| MONDO | 0011391 | E | validated | |
| MeSH | C536141 | E | validated | |
| UMLS | C1858854 | E | validated | |
| GARD | 3445 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
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Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (1):
- ORPHA:68356Leukodystrophy
rare genetic diseases; rare neurological diseases
No children.
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Genes
4 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| AQP4 | Disease-causing germline mutation(s) in | Assessed | HGNC:637 | ENSG00000171885 | 600308 | 18q11.2 | aquaporin 4 | 37143309[PMID] |
| GPRC5B | Disease-causing germline mutation(s) in | Assessed | HGNC:13308 | ENSG00000167191 | 605948 | 16p12.3 | G protein-coupled receptor class C group 5 member B | 37143309[PMID] |
| HEPACAM | Disease-causing germline mutation(s) in | Assessed | HGNC:26361 | ENSG00000165478 | 611642 | 11q24.2 | hepatic and glial cell adhesion molecule | 20301707[PMID] |
| MLC1 | Disease-causing germline mutation(s) in | Assessed | HGNC:17082 | ENSG00000100427 | 605908 | 22q13.33 | modulator of VRAC current 1 | 20301707[PMID] |
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Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 100 cases | Worldwide | Case(s) | Validated | 21977097[PMID]_12189496[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
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HPO phenotypes
18 annotations · validated 2025-06-11| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Frequent (79-30%) | ||
| HP:0001251 | Ataxia | |
| HP:0000708 | Atypical behavior | |
| HP:6000461 | Cerebral subcortical cyst | |
| HP:0007341 | Diffuse swelling of cerebral white matter | |
| HP:0001268 | Mental deterioration | |
| HP:0002333 | Motor deterioration | |
| HP:0005490 | Postnatal macrocephaly | |
| HP:0001250 | Seizure | |
| HP:0001257 | Spasticity | |
| HP:0002317 | Unsteady gait | |
| Occasional (29-5%) | ||
| HP:0002071 | Abnormality of extrapyramidal motor function | |
| HP:0002305 | Athetosis | |
| HP:0000717 | Autism | |
| HP:0012762 | Cerebral white matter atrophy | |
| HP:0002312 | Clumsiness | |
| HP:0001332 | Dystonia | |
| HP:0001249 | Intellectual disability | |
| HP:0002133 | Status epilepticus | |
Annotation source: 20301707[PMID]_29079544[PMID]_38487253[PMID]_23079554[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/2478
- This record as JSON: /data/d/2478.json