Objective:

To determine the yield of genetic testing in adults with epilepsy across various testing types (exome sequence, gene panel, microarray) and across patient characteristics (type of epilepsy, intellectual disability, drug resistance, and family history of epilepsy).

Background:

Most studies of genetic testing for epilepsy have focused on pediatric populations. Less is known about the results of genetic testing for adult populations.

Design/Methods:

We conducted a retrospective review on patients (age 18 or older) with epilepsy who were seen in the neurogenetics clinics at Penn and CHOP and who underwent clinical genetic testing. All genetic testing orders were placed at the discretion of the ordering clinicians, and a single patient could undergo multiple tests. The pathogenicity of identified variants was determined using ACMG criteria and the clinical interpretation of the neurogenetics team. 

Results:

The patient cohort included 282 patients with an age range of 18-73 years (median 24). Of this population, 67 out of 282 patients (24%) received a genetic diagnosis. The epilepsy type that resulted in the highest diagnostic yield was DEE (41%). The diagnostic yield was higher for patients with intellectual disability (41%) vs. without (14%). The yield was similar for patients with drug resistant epilepsy (28%) vs. drug responsive epilepsy (23%) (chi-squared p = 0.07). The age at testing was not significantly associated with the likelihood of a genetic diagnosis (Wilcoxon p = 0.74). Diagnostic yield was highest for exome sequencing (38%), but also substantial for gene panels (14%) and microarray (27%). The 67 genetic diagnoses represented 53 unique genes/loci, highlighting the genetic heterogeneity of epilepsy. 

Conclusions:

The yield of genetic testing in adults with epilepsy is substantial, and similar to the yield in pediatric populations. Healthcare providers should perform genetic testing in appropriately selected patients regardless of age.