Introduction: Megalencephalic leukoencephalopathy with subcortical cysts is a rare disease with autosomal recessive inheritance.
Materials and methods: Two brothers born from a consanguineous marriage, presenting with the phenotype of the disease, their parents, brothers and sisters were examined. Magnetic resonance imaging of the brain was performed for the two patients. Sequence analysis of MLC1 (GenBank mRNA accession no. NM_OI5166) was performed for the patients using intronic primers. PCR restriction fragment length polymorphism analysis was done in patients, their parents and in 100 Lebanese controls in order to exclude gene polymorphism.
Results: The clinical features were characteristic of the disease, consisting of an early-onset macrocephaly followed by slowly progressive ataxia, pyramidal tract involvement and epileptic seizures. In one patient, the clinical manifestations were aggravated by a trivial brain trauma. In his brother and in one female cousin, a status epilepticus was precipitated by a febrile syndrome. The diffuse cerebral white matter lesions and the subcortical temporo-polar and frontal cysts, best seen on MRI, allowed making the diagnosis. Molecular genetics revealed a new mutation involving the MLC1 gene (263G-->T, exon 3). As a consequence, it affects the second transmembrane domain predict (G88V) of the MLC protein (protein sequence NP_055981). The mutation was confirmed by PCR restriction fragment length polymorphism analysis.
Conclusion: Megalencephalic leucoencephalopathy with subcortical cysts may be individualized on clinical and radiological basis and confirmed by molecular genetics. In this Lebanese family, a new mutation of the MLC1 gene is reported.