Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare form of leukodystrophy.
The clinical manifestations are early onset ataxia followed by pyramidal signs and progressive mental deterioration.
The prevalence is not known, but the disease is more common in populations with high inbreeding.
This syndrome is characterized by megalencephaly developing during the first year of life.
Magnetic resonance imaging (MRI) shows severe and early white matter involvement although the neurological manifestations during the early stages of the disease are relatively mild. In addition to a diffuse T2 hypersignal of white matter, MRI finds a dense hypointense in T1 and FLAIR (Attenuation Inversion Recovery Fluid) of cysts in the temporal lobes and in the subcortical frontoparietal regions.
These severe neurological abnormalities are overall concomitant with clinical signs which are more moderate than those found in other forms of childhood leukodystrophies.
In the more advanced stages of the disease, cognitive deterioration slowly appears that contributes significantly to overall disability.
Early learning difficulties are observed in some patients from the first years of schooling.
MLC is an autosomal recessive inherited disease. Mutations in the MLC1 gene (22q13.3), the function of which is still unknown, have been identified in families with different ethnic origins. Some patients do not carry MLC1 mutations and there is genetic heterogeneity among some siblings. No specific therapy exists for MLC.
Management of the disease
Management is based on physiotherapy, psychomotor stimulation and treatment of seizures.