an asymptomatic case of megalencephalic leukoencephalopathy with subcortical cysts

Megalencephalic leukoencephalopathy with subcortical cysts (mlc), a demyelination leukodystrophy, is usually characterized by early-onset macrocephaly and gradually progressive motor and mild mental deterioration. variable clinical expression has been reported in mlc especially in adult cases. in this study, a multi affected family with variable phenotypes including an asymptomatic adult individual is reported to expand the clinical spectrum of mlc. a seven-year old boy was referred to our hospital due to macrocephaly and gait disturbance. according to brain magnetic resonance imaging (mri) findings, molecular studies were done to confirm the probable diagnosis of mlc in index case followed by family segregation analysis. a homozygous splice site variant, c.177+1g>t in mlc1 gene was found in proband, his mother and two aunts. aunts were clinically affected but his mother had no clinical symptoms despite bi-allelic mutation in milc1. the clinical data and available mri findings were reviewed for these cases. a comprehensive search was conducted on clinical variations of mlc. phenotypic variability and/or reduced penetrance are important phenomena in mlc. we extended phenotypic variation in mlc by reporting an asymptomatic adult case with a known pathogenic mutation in mlc1 gene.