February 14, 2023

Clinical Utility of Exome Sequencing in a Pediatric Epilepsy Cohort

Abstract found on Wiley Online Library

Objective: Exome sequencing (ES) has played an important role in the identification of causative variants for individuals with epilepsy and has proven to be a valuable diagnostic tool. Less is known about its clinical utility once a diagnosis is received. This study systematically reviewed the impact of ES results on clinical decision-making and patient care in a pediatric epilepsy cohort at a tertiary care medical center.

Methods: Pediatric subjects with unexplained epilepsy were referred by their neurologist, and informed consent was obtained through an institutional-review-board-approved research ES protocol. For those who received a genetic diagnosis, a retrospective chart review was completed of the probands and their relatives’ medical records prior to and after genetic diagnosis. The following outcomes were explored: provider management recommendations, changes in care actually implemented, and anticipatory guidance provided regarding the proband’s condition.

Results: Fifty-three probands met inclusion criteria. Genetic diagnosis led to at least one provider recommendation in 41.5% (22/53) families. Recommendations were observed in the following categories: medication, screening for non-neurological comorbidities/referrals to specialists, referrals to clinical research/trials, and cascade testing. Anticipatory guidance including information about molecular diagnosis, prognosis, and relevant foundations/advocacy groups was also observed.

Significance: Results demonstrate the clinical utility of exome sequencing (ES) for individuals with epilepsy across multiple aspects of patient care, including anti-seizure medication (ASM) selection, screening for non-neurological comorbidities and referrals to appropriate medical specialists, referral to reproductive genetic counseling, and access to research, information, and support resources. To our knowledge, this is the first study to evaluate the clinical utility of ES for a pediatric epilepsy cohort with broad epilepsy phenotypes. This work supports the implementation of ES as part of clinical care in this population.