Megalencephalic leukoencephalopathy with subcortical cysts

General Information (adopted from Orphanet):

Synonyms, Signs: MLC
Van der Knaap syndrome
Megalencephalic leukodystrophy
Vacuolating megalencephalic leukoencephalopathy with subcortical cysts
Megalencephaly - cystic leukodystrophy
Number of Symptoms 11
OrphanetNr: 2478
OMIM Id: 604004
613925
613926
ICD-10: E75.2
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: < 100 cases [Orphanet]
Inheritance: Autosomal dominant
Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Leukodystrophy
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
(HPO:0000256) Macrocephaly 298 / 7739
2
(HPO:0001256) Intellectual disability, mild 141 / 7739
3
(HPO:0001257) Spasticity 251 / 7739
4
(HPO:0001251) Ataxia 413 / 7739
5
(HPO:0001270) Motor delay 322 / 7739
6
(HPO:0001250) Seizures 1245 / 7739
7
(HPO:0001355) Megalencephaly 39 / 7739
8
(HPO:0006943) Diffuse spongiform leukoencephalopathy 2 / 7739
9
(HPO:0007341) Diffuse swelling of cerebral white matter 5 / 7739
10
(HPO:0003593) Infantile onset 249 / 7739
11
(HPO:0000007) Autosomal recessive inheritance 2538 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Diagnosis GeneReviews The diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC) can be made with confidence in individuals with typical clinical findings and characteristic abnormalities on cranial magnetic resonance imaging (MRI) [van der Knaap et al 1995, Singhal et al 1996, Topçu et al 1998]....
Clinical Description GeneReviews The two phenotypes observed in megalencephalic leukoencephalopathy with subcortical cysts (MLC) are the classic phenotype and the atypical improving phenotype. When associated with biallelic mutation of MLC1, the classic phenotype is known as MLC1; when caused by biallelic mutation of HEPACAM it is known as MLC2A. The improving phenotype associated with heterozygous mutation of HEPACAM is known as MLC2B....
Genotype-Phenotype Correlations GeneReviews Classic MLC. No phenotypic difference is evident between individuals with MLC who have identifiable mutations in MLC1 (MLC1) and those who have MLC associated with identifiable mutations in HEPACAM (MLC2A)....
Differential Diagnosis GeneReviews The differential diagnosis of macrocephaly and a diffuse leukoencephalopathy is limited; it includes Canavan disease, Alexander disease, infantile-onset GM2 gangliosidosis, and, on occasion, infantile-onset GM1 gangliosidosis and L-2-hydroxyglutaric aciduria (see Organic Acidemias Overview). Some children with congenital muscular dystrophy caused by laminin alpha-2 (merosin) deficiency (also known as MDC1A) have macrocephaly. The clinical features and course of these disorders are usually different from those of MLC. If the head circumference is well within the normal limits at age one year, it is highly unlikely that the infant has MLC. None of these disorders shares all the MRI characteristics of megalencephalic leukoencephalopathy with subcortical cysts (MLC). ...
Management GeneReviews To establish the extent of disease in an individual diagnosed with megalencephalic leukoencephalopathy with subcortical cysts (MLC) the following evaluations are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....