Unraveling the genetic basis of epilepsy: Recent advances and implications for diagnosis and treatment

Brain Res. 2024 Nov 15:1843:149120. doi: 10.1016/j.brainres.2024.149120. Epub 2024 Jul 18.

Abstract

Epilepsy, affecting approximately 1% of the global population, manifests as recurring seizures and is heavily influenced by genetic factors. Recent advancements in genetic technologies have revolutionized our understanding of epilepsy's genetic landscape. Key studies, such as the discovery of mutations in ion channels (e.g., SCN1A and SCN2A), neurotransmitter receptors (e.g., GABRA1), and synaptic proteins (e.g., SYNGAP1, KCNQ2), have illuminated critical pathways underlying epilepsy susceptibility and pathogenesis. Genome-wide association studies (GWAS) have identified specific genetic variations linked to epilepsy risk, such as variants near SCN1A and PCDH7, enhancing diagnostic accuracy and enabling personalized treatment strategies. Moreover, epigenetic mechanisms, including DNA methylation (e.g., MBD5), histone modifications (e.g., HDACs), and non-coding RNAs (e.g., miR-134), play pivotal roles in altering gene expression and synaptic plasticity, contributing to epileptogenesis. These discoveries offer promising avenues for therapeutic interventions aimed at improving outcomes for epilepsy patients. Genetic testing has become essential in clinical practice, facilitating precise diagnosis and tailored management approaches based on individual genetic profiles. Furthermore, insights into epigenetic regulation suggest novel therapeutic targets for developing more effective epilepsy treatments. In summary, this review highlights significant progress in understanding the genetic and epigenetic foundations of epilepsy. By integrating findings from key studies and specifying genes involved in epigenetic modifications, we underscore the potential for advanced therapeutic strategies in this complex neurological disorder, emphasizing the importance of personalized medicine approaches in epilepsy management.

Keywords: Diagnostics; Epigenetic; Epilepsy; Genetics; Mutations; Therapeutics.

Publication types

  • Review

MeSH terms

  • Animals
  • Epigenesis, Genetic / genetics
  • Epilepsy* / diagnosis
  • Epilepsy* / genetics
  • Epilepsy* / therapy
  • Genetic Predisposition to Disease* / genetics
  • Genetic Testing / methods
  • Genome-Wide Association Study
  • Humans