Factors Associated with Drug-resistant Epilepsy in Patients with Pediatric-onset Genetic Epilepsy
Abstract number :
1.347
Submission category :
4. Clinical Epilepsy / 4D. Prognosis
Year :
2024
Submission ID :
1356
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: John Schreiber, MD – Children’s National Hospital, George Washington University School of Medicine & Health Sciences, Washington, DC
Julie Ziobro, MD/PhD – University of Michigan
Nadee Dayananda, MBBS, MSc – Oregon Health & Sciences University
Sonal Bhatia, MBBS, MD – Medical University of South Carolina
Senyene E. Hunter, MD, PhD – University of North Carolina at Chapel
Cynthia Keator, MD – CookChildren's Health care System
Cemal Karakas, MD – University of Louisville School of Medicine/Norton Children's Hospital
Anthony Fine, MD – Department of Pediatric Neurology, Mayo Clinic, Rochester MN USA
Debopam Samanta, MD – University of Arkansas for Medical Sciences
Katherine Xiong, MD – Stanford University
Julie Sturza, MPH – University of Michigan
Jason Coryell, MD – Oregon Health and Sciences University/Doernbecher Children's Hospital
Rationale: Our ability to identify a genetic etiology in epilepsy has grown substantially over the past decade. The current yield of positive results from epilepsy gene panels or whole exome/genome sequencing (WES/WGS) is approximately 30-50% in patients with drug-resistant epilepsy (DRE) of unknown cause. However, while our diagnostic capabilities have flourished, our ability to use this diagnostic information to inform counseling and treatment has lagged. We aimed to examine factors associated with pediatric DRE with genetic etiologies to aid in prognostication.
Methods: We leveraged a multicenter database, created in 2021 by the Pediatric Epilepsy Research Consortium Genetics special interest group, recording clinician-derived data on genetic testing and seizure/epilepsy characteristics in pediatric patients with seizures and a pathogenic, likely pathogenic, or potentially causative variant of uncertain significance (VUS) identified on genetic testing. For this analysis, seven centers had contributed patient data. Statistical analysis was performed using SAS software.
Results: This analysis included 288 patients. Positive genetic tests included 176 gene panels, 55 WES, 34 chromosome microarrays, 10 single gene tests, 4 karyotypes, 7 FISH, 3 WGS, and 21 others. Seventeen had both positive WES and gene panel. A total of 130 patients had DRE; 115 did not. The remainder were not classified. Patients with DRE had younger age of seizure onset (median 0.5 years, IQR 0.5-3.5 vs 2.5 years, IQR 0.5-4.5) (p=0.003), higher prevalence of a developmental delay (DD)/intellectual disability (ID) and/or autism (95/130, 73% vs 53/115, 46%) (p < 0.05) and longer epilepsy duration (median 77 months, IQR 44-114) than those without DRE (median 50 months, IQR 32-99) (p < 0.05). Younger age of seizure onset was also associated with DD/ ID (median 0.5 years, IQR 0.5-3.5 vs 2.5 years, IQR 1.5-6.5 years). Finally, we found no difference in the proportion of DRE in patients with a positive gene panel (77/151 = 51%), positive WES (17/33 = 52%), or both positive gene panel and WES (11/17 = 65%) (p=0.6).
Clinical Epilepsy