Authors :
Presenting Author: Ahmad Zrik, MD – Baylor College of Medicine- Texas Children Hospital
Briana Miskey, DO – University at Buffalo
Mohamad Qadeer Farooqui, MD – University at Buffalo
Sanjana Suresh, Medical student – University at Buffalo
Osman Farooq, MD – University at Buffalo
Arie Weinstock, MD – Jacobs School Of Medicine And Biomedical Sciences, Buffalo, NY
Rationale: Epilepsy is a neurological disorder marked by recurrent seizures and diverse causes. Advances in genetic testing have improved diagnosis and personalized treatment. Common methods include multigene epilepsy panels, whole exome sequencing (WES), and whole genome sequencing, with gene panels often preferred for their lower cost, faster results, and broader insurance coverage. Genetic testing enhances diagnostic accuracy, informs treatment choices, avoids harmful medications, guides non-drug therapies, and supports specialist referrals and monitoring for comorbidities. It also benefits families through genetic counseling and informed planning. This study evaluates the use of multigene epilepsy panels in pediatric patients at the University at Buffalo, hypothesizing that early genetic diagnosis improves treatment initiation, prognosis, and caregiver satisfaction.
Methods:
This retrospective chart review analyzes clinical, electroencephalographic (EEG), and genetic data from pediatric epilepsy patients (infancy to 18 years) who underwent Invitae's Epilepsy Gene Panel testing between 2022 and 2024 and were found to carry a pathogenic variant. Data collected included demographics (age, sex), clinical features (seizure types and classification, age of onset, frequency, and other manifestations), medical history and comorbidities, EEG findings, and neuroimaging results
Results:
Between 2022 and 2024, a total of 161 epilepsy gene panels were performed. Pathogenic or likely pathogenic variants were identified in 30 patients, yielding a diagnostic yield of 18.6%. Of these, 13 patients were found to have pathogenic variants in the carrier state.
Among the 30 patients with abnormal genetic findings, 18 (60%) were male and 12 (40%) were female. The overall age range of affected patients was 1 to 18 years, with a mean age of 4.0 years (SD = 4.78). The age at the time of gene panel testing ranged from 1 month to 17 years, with a mean age of 1.0 year (SD = 4.63). Regarding the epilepsy classification, 53% of patients had focal epilepsy, 30% of patients had generalized epilepsy, 7% of patients had combined focal and generalized epilepsy, and 10% of patients remained unclassified.
Fifteen patients (50%) were identified as having intractable epilepsy. A positive family history of epilepsy in first-degree relatives was reported in 4 patients (13%). MRI brain findings revealed lesional abnormalities in 11 patients (37%).
Following identification of pathogenic variants, 26 patients (86%) were referred for genetic counseling to facilitate parental testing and to discuss reproductive risks. 20 patients (67%) were referred to subspecialty clinics based on the specific genetic findings, and 9 patients (30%) underwent changes in anti-seizure medication as part of the management plan informed by the gene panel results, 8 of whom (89%)of whom had a more than 90% of seizure reduction thereafter in their seizures frequency.
Conclusions: This study supports the growing evidence for genetic testing in pediatric epilepsy, highlighting its potential to guide personalized treatment and monitoring. Despite limited long-term data, early gene panel testing is increasingly recommended to improve outcomes.
Funding: None