Utility of genetic testing in the pre-surgical evaluation of children with drug-resistant epilepsy

• Published in: Journal of neurology 2024-05, Vol.271 (5), p.2503-2508
• Main Authors: Alsubhi, Sarah, Berrahmoune, Saoussen, Dudley, Roy W. R., Dufresne, David, Simard Tremblay, Elisabeth, Srour, Myriam, Myers, Kenneth A.
• Format: Article
• Language: English
• Subjects: Adolescent; Child; Child, Preschool; Chromosome 20; Diagnosis; Drug resistance; Drug Resistant Epilepsy - diagnostic imaging; Drug Resistant Epilepsy - genetics; Drug Resistant Epilepsy - surgery; Electroencephalography; Epilepsies, Partial - diagnosis; Epilepsies, Partial - diagnostic imaging; Epilepsies, Partial - genetics; Epilepsies, Partial - surgery; Epilepsy; Female; Genetic screening; Genetic Testing; Humans; Infant; Magnetic Resonance Imaging; Male; Medicine; Medicine & Public Health; Neuroimaging; Neurology; Neuroradiology; Neurosciences; Original Communication; Patients; Pediatrics; Preoperative Care; Retrospective Studies; Sodium channels (voltage-gated); Surgery
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-023-12174-3

We evaluated the utility of genetic testing in the pre-surgical evaluation of pediatric patients with drug-resistant focal epilepsy. This single-center retrospective study reviewed the charts of all pediatric patients referred for epilepsy surgery evaluation over a 5-year period. We extracted and analyzed results of genetic testing as well as clinical, EEG, and neuroimaging data. Of 125 patients referred for epilepsy surgical evaluation, 86 (69%) had some form of genetic testing. Of these, 18 (21%) had a pathogenic or likely pathogenic variant identified. Genes affected included NPRL3 (3 patients, all related), TSC2 (3 patients), KCNH1 , CHRNA4 , SPTAN1 , DEPDC5 , SCN2A , ARX , SCN1A , DLG4 , and ST5 . One patient had ring chromosome 20, one a 7.17p12 duplication, and one a 15q13 deletion. In six patients, suspected epileptogenic lesions were identified on brain MRI that were thought to be unrelated to the genetic finding. A specific medical therapy choice was allowed due to genetic diagnosis in three patients who did not undergo surgery. Obtaining a molecular diagnosis may dramatically alter management in pediatric patients with drug-resistant focal epilepsy. Genetic testing should be incorporated as part of standard investigations in the pre-surgical work-up of pediatric patients with drug-resistant focal epilepsy.