Focal cortical dysplasia as a cause of epilepsy: the current evidence of associated genes and future therapeutic treatments

TL;DR

Focal cortical dysplasia (FCD) is a leading cause of treatment-resistant epilepsy in children, linked to genetic mutations affecting brain development, with ongoing research into targeted therapies.

Contribution

This paper reviews current evidence on genetic factors involved in FCD and discusses future directions for targeted therapeutic treatments.

Findings

Genetic mutations in neuronal development genes are associated with FCD.

FCD often involves abnormal brain development due to gene mutations.

Research into molecular targets for FCD treatment is ongoing.

Abstract

Focal cortical dysplasias (FCDs) are the most common cause of treatment resistant epilepsy affecting the pediatric population. Most individuals with FCD have seizure onset during the first five years of life and the majority will have seizures by the age of sixteen. Many cases of FCD are postulated to be the result of abnormal brain development in utero by germline or somatic gene mutations regulating neuronal growth and migration during corticogenesis. Other cases of FCD are thought to be related to infections during brain development, or even other causes still unable to be fully determined. Typical anti-seizure medications are oftentimes ineffective in FCD as well as surgery is unable to be successfully performed due to the involvement of eloquent areas of the brain or insufficient resection of the epileptogenic focus, posing a challenge for physicians. The genetic nature of FCD provides an avenue for drug development with several genetic and molecular targets undergoing study over the last two decades.