Mutation in LS1 gene on chromosome 17. Males have severe lissencephaly. Females have milder disease. Arrested migration of neurons between the periventricular subependymal plate and the cortical gray matter. Mutation in doublecortin, an intracellular signaling molecule, having phosphorylation motifs for signaling kinases.
Family history shows reduced males in the pedigree.
Females have normal neurologic development but develop partial seizures with secondary generalization. MRI shows heterotopias in the walls of the ventricles bilaterally. These neurons did not migrate or undergo apoptosis. Mutation in filamin 1, an actin-binding phosphoprotein, causes truncation of the protein Filamin 1 is part of the cytoskeletal regulatory system that plays a role in neuronal migration. Aicardi's syndrome X-linked dominant with lethal effects on the male embryo.