The Yield of Genetic and Metabolic Testing in Epileptic Spasms

Objectives: To evaluate the yield of genetic and metabolic testing in patients with epileptic spasms (ES).

Background: ES are a challenging type of seizures with huge implications. Identifying the etiology in a cost-effective manner helps in management, utilization of personalized therapeutics and prognostication.

Methods: Retrospective review of the medical records of patients with ES who were treated at King Fahad Specialist Hospital, in Saudi Arabia, between 2009 and 2020. Pediatric patients less than 16-year-old presenting with ES and diagnosed by video-EEG were included.

Our centers approach in ES workup was to start with clinical assessment and neuroimaging. If the etiology was not identified, we ordered metabolic and/or genetic work up.

Results: We identified (n=121) patients with ES during the study period. Among these patients, an etiology was identified in 58 patients by clinical and imaging studies, while the remaining (n=63, 52%) patients required further workup. Metabolic testing helped identify the etiology in 5.3% of patients tested, while genetic testing identified the etiology in 41.2% of patients tested, with varying yield of each test. WES provided the highest testing yield, as 52% of WES tests provided a final diagnosis compared with comprehensive genetic panel (28.1%), and targeted gene testing (10%).

Conclusions: Metabolic workup has a low yield in identifying ES etiology. Genetic workup, on the other hand, had a high yield in identifying the etiology of ES when initial clinical assessment and neuroimaging were non-contributory. WES, in our cohort, was the most cost-effective genetic test in determining the etiology of ES.
Keywords: Epileptic spasms, infantile spasms, genetic testing