Clinical utility of exome sequencing in a pediatric epilepsy cohort

Jordana L Graifman; Natalie C Lippa; Maureen S Mulhern; Amanda L Bergner; Tristan T Sands

doi:10.1111/epi.17534

Clinical utility of exome sequencing in a pediatric epilepsy cohort

Epilepsia. 2023 Apr;64(4):986-997. doi: 10.1111/epi.17534. Epub 2023 Feb 21.

Authors

Jordana L Graifman¹, Natalie C Lippa^{1

2

3}, Maureen S Mulhern^{1

4

5}, Amanda L Bergner^{1

6}, Tristan T Sands^{2

4}

Affiliations

¹ Genetic Counseling Graduate Program, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
² Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, New York, USA.
³ Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
⁴ Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
⁵ Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
⁶ Department of Genetics and Development, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.

PMID: 36740579
DOI: 10.1111/epi.17534

Abstract

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 patients with unexplained epilepsy were referred by their neurologist, and informed consent was obtained through an institutional review board-approved research ES protocol. For patients 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 the inclusion criteria. Genetic diagnosis led to at least one provider recommendation in 41.5% families (22/53). 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 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.

Keywords: clinical decision-making; genetic testing; medical management; next-generation sequencing; outcomes.

MeSH terms

Epilepsy* / diagnosis
Epilepsy* / genetics
Exome Sequencing
Genetic Testing* / methods
Humans
Phenotype
Retrospective Studies