Clinical utility of genetic testing in pediatric drug-resistant epilepsy: A pilot study
Introduction
Advancing technology in the areas of genetics and genomics has opened new avenues for diagnosis and understanding human disease. Tests that were previously solely the purview of research are now available commercially and, in some cases, direct-to-consumer [1]. Genetic testing can allow specific diagnoses and may influence therapy selection. For example, patients with sodium channel mutations such as in Dravet syndrome should generally avoid carbamazepine and lamotrigine [2], and genetic polymorphisms can predict the profile of drug metabolism and propensity for severe allergic reactions [3].
Identifying a specific genetic diagnosis can prevent further unnecessary and invasive diagnostic testing as well as allow genetic counseling for family members. But some clinicians argue that many of these clinical decisions can be arrived at through clinical data without expensive and confusing genetic investigations [4]. It has been recommended that genetic testing in epilepsy should be used in only select cases [5]. However, specific guidelines for when to apply genetic testing, the cost effectiveness of various testing modalities, and the clinical and practical implications of such studies are not available [6], [7].
To start to address these questions, we reviewed in this study our experience with clinically available genetic studies and the implications of such testing on the diagnosis and management of pediatric drug-resistant epilepsy (PDRE) in our tertiary care center. Our goal was to describe, in retrospect, the yield of a variety of genetic testing modalities applied to our select referral population of patients.
Section snippets
Methods
In this retrospective chart review study, patients with PDRE were identified by reviewing records of all consecutive new patients seen in one pediatric epilepsy clinic during a 12-month period. Established patients who underwent whole exome sequencing (WES) during the study period were also included in the data collection (see Inclusion criteria below). The protocol was approved by the Duke IRB before starting the study.
Patient characteristics (Fig. 1, Table 1)
During the 12-month study period, 175 new patients were seen in one epilepsy clinic (Fig. 1). These included 37 patients (19 boys) with DRE. Of these 37, 25 underwent genetic testing. Of the remaining 144 patients, 47 had nonepileptic events such as syncope, psychogenic nonepileptic seizures, or other behavioral spells, and 91 patients had epileptic events that either did not further recur, were responsive to medical therapy, or were indeterminate (seizure freedom was less than 3 times their
Patient characteristics
Our pilot data presented in this study are based on patients referred to our pediatric epilepsy clinic in a tertiary care center. Our cohort is likely not to be representative of patient populations at many other centers. However, there are similarities of our patients to previous reports of pediatric epilepsy populations. Pediatric drug-resistant epilepsy accounts for 9–24% of cases of pediatric epilepsy and represents a significant portion of the disease burden of pediatric epilepsy [30]. The
Disclosure
Neither of the two authors has a conflict of interest.
Acknowledgments
We thank the staff of the Duke Pediatric Epilepsy Clinic and of the Division of Pediatric Neurology, and our colleagues and staff in Genetics, Clinical Neurophysiology and Laboratory Medicine. Special thanks to Karen Cornett, Tara McKellar, and Blythe Devlin for their invaluable assistance in the regulatory issues and planning of this study.
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Identification of Novel Gene Variants in Children With Drug-Resistant Epilepsy: Expanding the Genetic Spectrum
2023, Pediatric NeurologyCitation Excerpt :In this retrospective study, we found a high incidence of gene-related DRE in children (25 of 45; 55.5%). This yield was higher than expected given that the other three DRE studies had a diagnostic yield of approximately 5%, 20%, and 30%.27-29 This high rate of variant detection might be associated with our study material being different from previous studies.
Evaluation and management of drug resistant epilepsy in children
2021, Current Problems in Pediatric and Adolescent Health CareThe role of targeted gene panel in pediatric drug-resistant epilepsy
2020, Epilepsy and BehaviorCitation Excerpt :There is by far only one Taiwan study on gene panel analysis in children with epilepsy, focusing on pediatric patients with epilepsy and developmental delay/mental retardation, and the mutation identification rate was 29.5% [10]. Previous studies have found that genetic diagnoses are often associated with generalized epilepsy, epileptic encephalopathy, and/or medically intractable, nonlesional epilepsies [8,11]. In our study, most patients with genetic diagnosis had fever-associated epilepsy, indicating the role of targeted gene panel in diagnosis of patients with fever-associated epilepsy.
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Current address: Nationwide Children's Hospital, Columbus, OH, USA.