Publication

Isolated lissencephaly sequence and double-cortex syndrome in a German family with a novel doublecortin mutation

Journal Paper/Review - Aug 1, 2000

Units
PubMed
Doi

Citation
Aigner L, Flügel D, Dietrich J, Ploetz S, Winkler J. Isolated lissencephaly sequence and double-cortex syndrome in a German family with a novel doublecortin mutation. Neuropediatrics 2000; 31:195-8.
Type
Journal Paper/Review (English)
Journal
Neuropediatrics 2000; 31
Publication Date
Aug 1, 2000
Issn Print
0174-304X
Pages
195-8
Brief description/objective

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 DCIILS. 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.