Genetic and Electrophysiologic Study in Focal Drug-resistant Epilepsies

Fondation Ophtalmologique Adolphe de Rothschild450 enrolled

Overview

Brain somatic mutations are increasingly recognized as a major cause of focal epilepsies. These include mTOR pathway mutations underlying cortical malformations such as focal cortical dysplasia and hemimegalencephaly, and SLC35A2 mutations in MOGHE, and activating variants in the SHH pathway in hypothalamic hamartomas. This study aims to identify brain somatic mutations using paired blood-brain samples and trace DNA from stereo-EEG electrodes, and to perform functional validation of candidate variants in children with drug-resistant focal epilepsy.

Study Type

OBSERVATIONAL

Enrollment

450

Conditions

Drug-resistant Focal Epilepsies in Pediatric Population

Interventions

Sampling of blood, frozen resected tissues, and cerebrospinal fluid (CSF)GENETIC

Sampling of blood, frozen resected tissue, saliva, and cerebrospinal fluid (CSF); sequencing of paired blood-brain DNA samples, SEEG electrodes

Medical Language ↔ Plain English

Inclusion Criteria: * Children with focal drug-resistant epilepsy including Focal Cortical Dysplasia, Hemimegalencephaly, Tuberous Sclerosis, Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE), Hypothalamic Hamartomas, Sturge-Weber syndrome, Rasmussen encephalitis, gliomas * Their parents who have signed informed consent 1) for their child's participation (for parents) and 2) for themselves * Social security coverage or foreign regime recognized in France Exclusion Criteria: * refusal to participate in the study * contraindication to anaesthesia, to MRI or to surgery * no medical insurance coverage

Outcomes

Primary Outcomes

qualitative genetic analysis

Detection of brain somatic mutations and functional studies

Time frame: baseline

Central Contacts

Amelie YAVCHITZ, MD

CONTACT

+33 1 48 03 64 54 ayavchitz@for.paris

Mathilde CHIPAUX, MD, PhD