Prenatal insult to teratogenic, physical, and biological environmental factors such as alcohol, cocaine, trauma, irradiation, and viruses has been implicated to contribute in the development of malformations of cortical development (MCD). The molecular and biochemical signals that control proliferation, migration, and organization of the cells involved in malformed cerebral cortical development remain to be clearly understood. Mutations in more than 72 genes have been identified to be involved in different forms of MCD. Some of the MCD-related genes include TSC1, TSC2, LIG1, DCX, FCMD, SCN1A, SCN2A, SCN1B, GABRG2, DNA polymerase gamma, mitochondrially encoded tRNA(Lys), VDAC1&2, and MnSOD. In addition to gene mutations, single nucleotide polymorphisms in the KCNJ10 potassium channel gene have been reported to increase seizure susceptibility in a variety of epilepsy subtypes. It has become increasingly clear that many malformations of the human cortex result from the action of defective genes. Epigenetic changes in various epileptic syndromes have also been reported. It appears that MCD and some of the sporadic epilepsy result from gene mutations or epigenetic changes that lead to altered gene function. A complex interplay between epigenetic, genetic, and genomic changes appears to be involved in the development of MCD, seizure onset, and epilepsy. Identifying the gene-environment interactions that cause disorders of human cerebral cortical development that are associated with abnormal growth of lesion and neuronal migration would be important for understanding cortical dysplasia pathogenesis.
