Clinical and genetic heterogeneity in megalencephalic leukoencephalopathy with subcortical cysts (MLC)

Background: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) was recently localized on chromosome 22q(tel) and 26 different mutations of the gene MLC1 have been found. We report three siblings of non-consanguineous parents who presented with characteristic features of MLC, but did not have MLC1 mutations. Methods: Clinical, laboratory and neuro-imaging findings of the siblings are described and similar patients with MLC are reviewed. Results: All three siblings suffered from ataxia, progressive severe tetraparesis, dysarthria, dysphagia and epilepsy. Generalized dystonia occurred in one patient. Mental deterioration progressed more slowly than motor deterioration. The youngest male was the most severely affected and died at the age of 23 years. The two older females are now 34 and 35 years old. Our patients are among the oldest described with this clinical entity. No mutation of the MLC1 gene was found in our siblings and linkage with the MLC1 locus was excluded. Conclusions: The genetic findings in our patients suggest at least a second gene locus for MLC.