Neurologist’s Black Swan: Molecular Basis of Prenatal Seizures

One of the least studied but clinically severe forms of epilepsy is seizures with prenatal manifestations. Our understanding of epilepsy disorders has advanced substantially; numerous disease-associated genes have been identified, classifications have been refined, and underlying mechanisms and diagnostic approaches have been elucidated. However, one group of patients-those with seizures before the birth-has remained largely overlooked by researchers, despite numerous similar clinical cases reported over the past two decades. To date, only two genes, <i>SCN2A</i> and <i>SCN8A</i>, have been shown to have pathogenic variants that are reliably related to fetal epilepsy. Yet, how many genes are truly involved? This review will examine the known molecular foundations of epilepsy with prenatal onset. The prevalence of fetal seizures in patients with epilepsy is likely underestimated, although timely diagnosis of the disease is crucial for patient outcomes.