Isolated Lissencephaly Sequence (ILS) and Double-Cortex Syndrome (DC) are neuronal heterotopias caused by developmental defects in neuronal precursor cell migration. We report on the clinical and genetic assessment of a German pedigree with DC/ILS. Affected males showed clinical symptoms typical of lissencephaly, i.e. seizures, severe mental retardation and extensive physical disability starting in the early postnatal period. Females, however, displayed a milder phenotype with epileptic seizures being the only clinical symptom of note. The MR imaging of a male ILS patient showed a smooth cortex with pachygyria, hydrocephalus and a diffuse, broad distribution of grey matter throughout the brain. In the affected female, a double cortex syndrome in the form of a subcortical bilateral band of grey matter was evident by MR imaging.
The molecular and genetic basis of DC/ILS is associated with mutations in the X-linked doublecortin gene (DCX). The genetic assessment of the family revealed a novel missense mutation 211 G → T in DCX exon 2 in affected family members. This mutation cosegregated with the clinical symptoms and resulted in a non-conservative amino acid substitution A71S. DCX is a microtubule-associated phosphoprotein and mutations in DCX might affect cytoskeletal dynamics and the regulation of cell migration.
Key words
Migration - Lissencephaly - Doublecortin - Double cortex - Epilepsy
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Dr. Ludwig Aigner
Department of Neurology VW-Foundation Junior Group University of Regensburg
Universitä:;tsstr. 84
93053 Regensburg
Germany
Email: E-mail: ludwig.aigner@klinik.uni-regensburg.de