Focal cortical dysplasia: Updates

Area of Science:

• Neuroscience
• Genetics
• Pathology

Background:

• Focal cortical dysplasias (FCDs) are a primary cause of drug-resistant epilepsy, particularly in pediatric patients.
• The International League Against Epilepsy (ILAE) classification categorizes FCDs into three types based on cortical layering and architectural abnormalities.
• Recent research highlights somatic mutations and mosaicism as key drivers of FCD development.

Purpose of the Study:

• To review the histopathological lesions associated with FCDs.
• To discuss the molecular pathogenesis underlying different FCD types, focusing on the mTOR pathway.
• To propose an updated classification for FCDs based on current molecular and pathological findings.

Main Methods:

• Review of existing literature on FCDs, including histopathology, genetic studies, and molecular mechanisms.
• Analysis of recent findings on somatic mutations and mosaicism in brain malformations.
• Discussion of the role of the mTOR signaling pathway in FCD type II pathogenesis.

Main Results:

• FCD type II pathogenesis is linked to mTOR pathway activation, with pathogenic variants found in up to 63% of cases.
• Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) shows recurrent pathogenic variants in SLC35A2 with mosaicism.
• Somatic mutations occurring during embryonal development are increasingly recognized as the cause of FCDs.

Conclusions:

• A deeper understanding of FCD molecular pathogenesis is crucial for accurate classification and potential therapeutic strategies.
• The proposed revised classification aims to integrate histopathological and molecular findings for improved diagnostic precision.
• Further research into the genetic underpinnings of FCDs will refine diagnostic criteria and inform treatment approaches for epilepsy.