Advances on the Genetics of Mendelian Idiopathic Epilepsies

Genetic factors play an increasingly recognized role in idiopathic epilepsies. Since 1995, positional cloning strategies in multi-generational families with autosomal dominant transmission have revealed 11 genes (KCNQ2, KCNQ3, CHRNA4, CHRNA2, CHRNB2, SCN1B, SCN1A, SCN2A, GABRG2, GABRA1, and LGl1) and numerous loci for febrile seizures and epilepsies. To date, all genes with the exception of LGl1 (leucine-rich glioma inactivated 1), encode neuronal ion channel or neurotransmitter receptor subunits. Molecular approaches have revealed great genetic heterogeneity, with the vast majority of genes remaining to be identified. One of the major challenges is now to understand phenotype-genotype correlations. This review focuses on the current knowledge on the molecular basis of these rare Mendelian autosomal dominant forms of idiopathic epilepsies.