Cellular and molecular basis of cerebral dysgenesis

Maldevelopment of the cerebral cortex, cortical dysgenesis (CD), may be associated with epilepsy, mental retardation (MR), and focal or widespread neurologic deficits. The histologic hallmark of CD is disrupted cytoarchitecture, including disorganized lamination, malpositioned neurons with respect to their normal radial orientation, abnormal dendritic arborization, and heterotopic neurons within the white matter. Seizures in these patients are particularly difficult to control with conventional anti-epileptic drugs (AEDs) and may require epilepsy surgery to remove these abnormal foci. Focal CD has been reported in up to 30% of epilepsy surgery specimens and are believed to provide the central pathologic substrate responsible for seizures in these patients. How and why CD results in epileptiform activity is unknown. Advances in understanding the pathogenesis of some types of CD have occurred recently with the cloning genes responsible for a few types of X-linked and autosomal CD. This review will outline the major subtypes of CD, the pathologic findings, and the molecular etiologies for a variety of CD. We will also address recent experimental advances in studying the pathogenesis of CD.