Genetic basis of developmental malformations of the cerebral cortex

Widespread use of noninvasive brain imaging techniques, in particular magnetic resonance imaging, has led to increased recognition of genetic disorders of cortical development in recent years. The causative genes for many of these disorders have been identified through a combination of detailed clinical and radiological analyses and molecular genetic approaches. These disease genes have been found to affect different steps of cortical development, including proliferation of neuronal progenitor cells, neuronal migration, and maintaining integrity of the pial surface. In many cases, syndromes with similar clinical phenotypes are caused by genes with related biochemical functions. In this article, we review the recent advances in molecular genetic studies of the disorders of cortical development. The identification and functional studies of the genes associated with these developmental disorders will likely lead to improvement in diagnosis and facilitate our understanding of the mechanisms of cortical development.