[PS13-2A-K] The genetic bases of cortical development and its disorders
Basic research pertaining to brain development, particularly the cerebral cortex, is rapidly progressing, and a demand for its clinical applications, such as molecular diagnosis and genetic counseling, is increasing. The recent classification scheme for the malformations of cortical development (MCD) is based on causative genes and molecular mechanisms as well as morphological findings. The advancement and dissemination of neuroimaging techniques, particularly magnetic resonance imaging, make it easier to diagnose many types of MCD but more complicated to classify them. In this keynote, I will address the genetic bases of cortical development and talk about a wide spectrum of MCD, forming a continuum from lissencephaly, through polymicrogyria, and ending in focal cortical dysplasia. In terms of molecular mechanisms based on causative genes, MCD may be classified into groups: interneuronopathies, caused by the ARX mutation; tubulinopathies, caused by mutations of tubulin-related genes; and mTORopathies, caused by mutations in the genes of the PIK3–AKT–mTOR signal transduction pathway. It is well known that patients with MCD frequently show epileptic seizures, which are usually refractory to medication. Mutations in some genes, such as ARX and DEPDC5, cause both MCD and epileptic syndromes without MCD. In the next generation of child neurology, a molecularly targeted therapy for the symptoms of MCD, including not only epileptic seizures but also intell