Genetic testing beneficial as a diagnostic tool for adults with epilepsy

Key takeaways:

• The study included 250 patients with epilepsy.
• A history of delayed development and earlier seizure onset were associated with a higher yield of pathogenic variants related to epilepsy.

ORLANDO — Genetic testing, which is likely to identify underlying genetic causes for the condition, should be a component of diagnostic evaluations for adult patients with epilepsy, according to new research.

“Genetic testing has become a standard component of the diagnostic evaluation for children with early onset epilepsies,” Yi Li, MD, PhD, lead study author and clinical assistant professor of neurology at Stanford University, and colleagues wrote in a presentation at the American Epilepsy Society annual meeting. “This information can help guide clinical decision-making when determining potential benefits of genetic testing in adult epilepsy patients.”

Li and colleagues sought to assess the diagnostic yield of genetic testing for adult epilepsy patients and to identify the risk factors associated with a higher likelihood of identifying genetic causes of epilepsy.

Their retrospective study was performed at Stanford University Hospital with a chart review of electronic health records by the university’s EHR cohort discovery tool between 2010 and 2023. The review identified 1,484 individuals diagnosed with epilepsy who had records of genetic testing during clinic visits; 806 of the patients were aged older than 16 years. A final chart review included 250 individuals aged older than 16 years (122 male, 128 female; mean age of seizure onset 12.0 +/- 12.9 years old with 18.1% experiencing onset before their first birthday).

Among the 215 individuals with known epilepsy types, 52% had focal epilepsy and the rest had generalized or mixed epilepsy. Genetic testing was conducted at a mean age of 24.5 +/- 13.6 years old.

The following genetic testing variations were performed: panel testing (n = 173), WES testing (n = 69), microarray (n = 38), single gene testing (n = 28), Fragile X testing (n = 26), karyotyping (n = 22), and mitochondrial testing (n = 13).

According to results, WES testing recorded the highest diagnostic yield (34.8%), followed by genetic panel testing (28.3%) and microarray testing (18.4%), while all tests collectively identified pathogenic variants in 95 patients (37.8%), additionally revealing that 137 patients (54.8%) had variants of uncertain significance findings, 17 had benign findings and 64 had negative findings.

Data further showed 91 (36.4%) patients’ genetic tests yielded pathogenic variants related to epilepsy, with the most common variants being mutations in TSC2 (15.4%), SCN1A (8.8%), TBC1D24, and TSC1 (4.4% each). Among patients with seizure onset after their first birthdays, DEPDC5, POLG, ATXN10, and TSC2 were the most frequently identified pathogenic variants (5.8% each).

History of developmental delay (r2 = 0.207) and earlier seizure onset age (r2 = -0.252) were associated with a higher yield of pathogenic variants related to epilepsy.

“Our study highlights a significant real-world delay in genetic testing of about 10 years from the first seizure,” Li said in a related release. “The price of genetic testing has decreased over time, so ideally more people with epilepsy won’t have to wait until they are adults to be tested.”

Reference:

• More than Four in 10 adults with epilepsy have a genetic link. https://aesnet.org/about/about-aes/press-room/more-than-four-in-10-adults-with-epilepsy-have-a-genetic-link-adults-with-unknown-cause-of-condition-should-get-tested-study-suggests. Published Dec. 1, 2023. Accessed Dec. 2, 2023.