Using the PERC Database to Gather Insights on Epilepsy Genetics: Julie Ziobro, MD, PhD; John Schreiber, MD

WATCH TIME: 5 minutes

"Patients with multiple comorbidities may face prolonged latency to genetic testing, often due to access barriers to genetic specialists or clinicians' hesitancy to order tests without additional guidance."

Recent advancements in genetic testing technologies, such as next-generation sequencing, have significantly enhanced clinicians’ ability to identify the genetic underpinnings of pediatric epilepsy. Findings from 2 studies presented at the recently concluded 2024 American Epilepsy Society Annual Meeting, held December 6-10, in Los Angeles, that utilized data from the Pediatric Epilepsy Research Consortium (PERC) database shed light on critical aspects of genetic testing, including access disparities, diagnostic latency, and implications for drug-resistant epilepsy (DRE).^1,2

One study, presented by lead author Julie Ziobro, MD, PhD, examined the latency between seizure onset and genetic testing in pediatric patients.¹ Analyzing data from 323 patients, researchers observed a median latency of 69 months to the first genetic test, with shorter latency associated with early seizure onset, infantile spasms, and developmental delay/intellectual disability (DD/ID). Notably, no significant disparities in latency were reported that concerned race, language, or socioeconomic factors, suggesting equitable access to testing across demographic groups in this cohort. However, the findings suggest a potential need for earlier intervention and awareness to reduce diagnostic delays and improve care pathways.

The other study, presented by John Schreiber, MD, explored the genetic and clinical profiles of pediatric patients with DRE. Among 288 patients with confirmed pathogenic or likely pathogenic variants, those with DRE had earlier seizure onset, higher prevalence of DD/ID and autism, and longer epilepsy duration compared with patients without DRE. Although the genetic testing methods, including gene panels and whole exome sequencing (WES), yielded comparable rates of DRE diagnosis, the study underscored the gap between genetic findings and their clinical application in treatment planning and prognostication.²

In an interview with NeurologyLive® at AES 2024, Schreiber, the director of epilepsy genetics at Children’s National Hospital, and Ziobro, an assistant professor of pediatrics at the University of Michigan, shared their perspectives on addressing critical gaps in epilepsy genetics. They discussed strategies to improve access to genetic testing for patients with rare epilepsies and complex comorbidities, emphasizing the importance of earlier access to genetic counseling in shaping outcomes for drug-resistant epilepsy. Additionally, they highlighted the potential value of expanding datasets to include more diverse populations, which could provide deeper insights into diagnostic latency and its impact on clinical care.

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REFERENCES
1. Ziobro J, Schreiber J, Dayananda N, et al. Factors Affecting Latency to Genetic Testing in Pediatric Epilepsies. Presented at: AES 2024; December 6-10; Los Angeles, CA. Abstract 1.311
2. Schreiber J, Ziobro J, Dayananda N, et al. Factors Associated with Drug-resistant Epilepsy in Patients with Pediatric-onset Genetic Epilepsy. Presented at: AES 2024; December 6-10; Los Angeles, CA. Abstract 1.347