Yield of Epilepsy Gene Panel Testing Among Adult and Pediatric Patients at a Regional Academic Medical Center
Marissa Kellogg1, Andrea Hildebrand2, Kathryn Matthews2, David Spencer3, Katherine Park4, Matthew McCaskill5, Lia Ernst2, Paul Motika2, Laura Bliss6, R Coryell6, Ittai Bushlin7
1Neurology, VA Portland Healthcare System, Dept of Neurology, 2Oregon Health and Science University, 3Oregon Health & Science University (OHSU), 4Oregon Health Sciences University, 5Oregon Health Science University, 6Doernbecher Childrens Hospital, 7Oregon Health & Science University
Objective:
To compare the yield of epilepsy gene panel testing (EGPT) between pediatric and adult patients tested at a regional academic medical center.
Background:
Age of seizure onset is inversely proportional to EGPT yield, yet there are few studies of EGPT yield in adults.
Design/Methods:
This single-center cohort study included all patients who underwent EGPT through a genetic testing company (Invitae) between 1/1/2016 and 9/16/2024. EGPT results were considered “positive” if reports included pathogenic (P) or likely pathogenic (LP) variants, “uncertain” if only variants of uncertain significance (VUS) were found (nothing pathogenic), and “negative” if no P/LP/VUS were identified in genes present on EGPT at the time of testing. Analysis was conducted as quality improvement to increase access to genetic testing and counseling resources.
Results:
823 unique patients underwent EGPT, including 526 (64%) peds and 297 (36%) adults (aged 18+ years at time of testing). Among pediatric results, there were 137 (26%) positives, 299 (57%) uncertain, and 90 (17%) negatives. Among adult results, there were 79 (27%) positives, 171 (58%) uncertain, and 47 (16%) negatives. EGPT size ranged from 80 epilepsy-associated genes in 2016 to over 350 in 2024. P/LP variants were most reported in the genes SCN1A (17), POLG (15), DEPDC5 (14), SZT2 (12), NPRL3 (11), SCN9A (11), DOCK7 (9), KCNQ2 (9), ADSL (8), KCNH2 (8) KCNT1 (8), PRRT2 (8), and SCN8A (8).
Conclusions:
Yield of EGPT was similar amongst pediatric and adult patients in this academic center’s cohort. Lower than expected pediatric yield was likely influenced by many pediatric patients undergoing whole exome sequencing instead of EGPT, while higher than expected adult yield was likely influenced by preferential testing of adults with childhood-onset epilepsy. A major study limitation is that true diagnostic yield of EGPT could not be calculated given limited adult access to formal medical geneticist consultation for definitive diagnosis.
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