Abstracts

Rationale: Molecular advances have allowed genetic testing to become part of routine epilepsy investigation, particularly amongst pediatric neurologists. However, genetic testing is not yet routinely incorporated in adult epileptology, and the diagnostic yield of different methods have yet to be established for adult epilepsy patients. The present study sought to determine the diagnostic yield of a commercial gene panel in adults with longstanding history of epilepsy and intellectual disability of any degree. Methods: This is a cross-sectional study analyzing the results of epilepsy gene panels including up to 185 genes in adult epilepsy patients with intellectual disability, according to DSM-V. Patients with acquired structural brain abnormalities or known chromosomal abnormalities were excluded. Results: From approximately 600 patients seen from January 2017 to June 2018 in one single academic epilepsy center, 64 probands and two affected relatives (32 males, mean age 31 years ± 10) were selected and clinically tested. Fourteen probands (14/64 = 22%; four males, mean age 32 y ± 10) were found to have pathogenic or likely pathogenic variants in the following genes: SCN1A (three probands), GABRB3 & UBE3A (two probands for both genes combined), KANSL1, SLC2A1, KCNQ2, SLC6A1, HNRNPU, STX1B, SCN2A, PURA, and CHD2 (one single proband for each gene). Six variants arose de novo, and the inheritance was not determined in eight. Nine probands (64%) had severe or profound intellectual disability, and five (35%) had autistic features. Eight patients (57%) had a diagnostic change from presumptive clinical diagnosis prior to genetic testing. The test sensitivity detecting relevant genetic information was not significantly different (p =0.57) between probands tested with the panel including 126 genes (27.7%) and larger panels ranging from 183 to 185 genes (19.1%). Conclusions: We were able to demonstrate that a commercial epilepsy gene panel can be an important resource in clinical practice, identifying the etiology in 22% of adults with epilepsy and intellectual disability. The diagnostic yield is similar to previously reported pediatric cohorts. Future work including larger population samples could be aimed at addressing the more prevalent genes linked to epilepsy in adulthood and whether these are similar or different than previously reported in pediatric cohorts. Funding: No funding