Brain Somatic Variants In Pediatric Epilepsy Patients

There is a lot more to be studied, but de novo somatic mutation leading to mosaic variants is identified as a causative etiology in a significant proportion of epilepsy patients due to malformation of cortical development (MCD). Here we are going to describe the experience of gene panel analysis for brain somatic variants in pediatric epilepsy patients receiving epilepsy surgery.

For the past 10 years, patients undergoing resective epilepsy surgery in Severance Children’s Hospital were subject to a brain somatic MCD gene panel using their resected brain tissues. Patients with structural etiology due to injury such as ischemia or hemorrhage, patients with hippocampal sclerosis as etiology of epilepsy, and patients who did not consent to the study enrollment were excluded from genetic analysis. Patients with tuberous sclerosis or long-term epilepsy-associated tumors were excluded from the analysis in the current study.

Of 237 patients tested, pathogenic variants were identified in 73 patients. Seizure onset age, seizure semiology, imaging findings, pathology, and EEG findings show significant differences among patients grouped by genes harboring pathogenic variants. Of note, mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) patients with somatic SLC35A2 variants are more likely to present as secondary developmental and epileptic encephalopathy with developmental impact than focal cortical dysplasia type 2 patients with somatic mTOR pathway variants.

Somatic variants can be pathogenic causes of MCD leading to epilepsy surgery in children, and there are differences in clinical characteristics among genotypes.