Rationale:
Genetic testing has become a standard component of the diagnostic evaluation for children with early onset epilepsies. The current study aims to assess the diagnostic yield of genetic tests for adult epilepsy patients, and identify the risk factors associated with a higher likelihood of identifying a genetic cause of epilepsy. This information can help guide clinical decision-making when determining the potential benefits of genetic testing in adult epilepsy patients.
Methods:
A retrospective study was performed at Stanford University Hospital with chart review of the electronic health record between 2010-2023. The Stanford electronic health record cohort discovery tool(STARR) was used to identify patients with ICD-10 codes of epilepsy and records of genetic testing in clinic visits.
Results:
A total of 1484 patients were identified and 806 of them were more than 16 years old (yo) from the STARR database. After chart reviews and assessing genetic testing availability, a final cohort of 250 patients more than 16 years old was included, comprising 122 males and 128 females. The mean age of seizure onset was 12.0 +/- 12.9 years old (yo), with 18.1% experiencing onset before age 1. Among the 215 patients 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 yo.
Different genetic testing types were performed: panel testing (173 patients), WES testing (69 patients), microarray (38 patients), single gene testing (28 patients), Fragile X testing (26 patients), karyotyping (22 patients), and mitochondrial testing (13 patients). Among the different types of genetic tests, WES yielded the highest diagnostic yield (34.8%), followed by genetic panel testing (28.3%), and microarray testing (18.4%). These tests collectively identified pathogenic variants in 95 patients (37.8%). Additionally, 137 patients (54.8%) had variants of uncertain significance findings, 17 had benign findings, and 64 had negative findings.
In total, 91 (36.4%) patients' genetic tests yielded pathogenic variants related to epilepsy. The most commonly identified variants included mutations in TSC2 (15.4%), SCN1A (8.8%), TBC1D24, and TSC1 (4.4% each). Among patients with seizure onset after age 1, DEPDC5, POLG, ATXN10, and TSC2 were the most frequently identified pathogenic variants (n=3, 5.8% each). Factors possibly associated with a higher risk of genetic epilepsy were examined, including family history, comorbid developmental delay, febrile seizures, status epilepticus, perinatal injury, and seizure onset age. History of developmental delay (r2=0.207, p=0.001) and earlier seizure onset age (r2=-0.252, p< 0.001) were associated with a higher yield of pathogenic variants related to epilepsy.