Malformations of cortical development: molecular pathogenesis and experimental strategies

Malformations of cortical development (MCD) are developmental brain lesions characterized by abnormal formation of the cerebral cortex and a high clinical association with epilepsy in infants, children, and adults. Despite multiple anti-epileptic drugs (AEDs), treatment of epilepsy associated with MCD may require cortical resection performed to remove the cytoarchitecturally abnormal region of cortex. Single genes responsible for distinct MCD including lissencephaly, subcortical band heterotopia, and tuberous sclerosis, have been identified and permit important mechanistic insights into how gene mutations result in abnormal cortical cytoarchitecture. The pathogenesis of MCD such as focal cortical dysplasia, hemimegalencephaly, and polymicrogyria, remains unknown. A variety of new techniques including cDNA array analysis now allow for analysis of gene expression within MCD.