Epilepsy: Genetics, Biomarkers, and advances toward Precision Medicine

Epilepsy is a heterogeneous neurological disorder characterized by recurrent, unprovoked seizures, with nearly one-third of patients remaining resistant to current therapies. Its multifactorial basis involves genetic, molecular, epigenetic, inflammatory, and metabolic contributors that drive disease heterogeneity. Genetic modifiers such as ion channel mutations (SCN1A, GABRA1, CHRNA4) and mTOR pathway disruptions (TSC1, DEPDC5), along with epigenetic mechanisms linking environmental influences to gene expression, play central roles in seizure susceptibility and treatment response. A broad spectrum of biomarkers-genetic, proteomic, metabolomic, imaging, and electrophysiological-provides critical insights for diagnosis, prognosis, and therapeutic strategies. Integrating molecular discoveries with clinical perspectives underscores the potential of biomarker-driven precision medicine, supporting targeted therapies, optimized patient stratification, and improved long-term outcomes in epilepsy.