Genetics of Epilepsy

Rare epilepsy syndromes encompass a spectrum of disorders influenced by genetic factors, ranging from single-nucleotide variants and copy number variants to chromosomal abnormalities. Advances in next-generation sequencing technologies have facilitated the discovery of monogenic causes of epilepsy, with over 1,000 implicated genes identified to date. Pathogenic variants can affect protein-coding, non-coding and mitochondrial DNA, influencing diverse biological processes. Chromosomal abnormalities and copy number variants disrupt multiple genes, posing diagnostic challenges but providing insights into syndromes such as ring chromosome 20. Expansions of short tandem repeats contribute to syndromes like progressive myoclonus epilepsy and familial adult myoclonus epilepsy. Additionally, polygenic contributions underscore the multifactorial nature of common epilepsies, suggesting future diagnostic and prognostic applications. Genetic analyses continue to transform the understanding and management of epilepsy.