Abstracts

Rationale: Many genes have been identified in the etiology of epilepsy and are available for clinical testing. However, the clinical utility of genetic testing, its yield and the population of patients most likely to benefit from such testing have not been determined. To address these questions we reviewed our experience with clinically available genetic testing and its implications in the diagnosis and management of drug resistant epilepsy (DRE) in a pediatric epilepsy clinic in our center. Methods: Retrospective chart review of all new patients seen in a pediatric epilepsy clinic in a one year period (July 20011-June 2012). Of 175 new patients seen, 37 had DRE as defined by the ILAE. 25 of these patients underwent genetic testing which included, depending on clinical judgment, one or more of the following: microarray (performed in 17 patients), karyotype (performed in 6 patients), single gene sequencing (16 patients), gene panels (13 patients) and/or exome (2 patients) or mitochondrial genome sequencing (1 patient). Clinical characteristics of the patients (testing vs no testing, positive vs. negative test results) were compared. We used t-test and Fisher exact test to identify the factors that predicted positive results on genetic testing and other associations.Results: Factors that were associated with genetic testing being ordered by the clinician were generalized epilepsy, the presence of developmental delay, and the presence of epileptic encephalopathy (p=0.005, 0.0005, 0.0022, respectively). Factors that were associated with positive genetic test results included generalized epilepsy (p=0.028) and epileptic encephalopathy (p=0.005). 40% (10) of the 25 patients undergoing genetic testing had findings that resulted in a specific genetic diagnosis. Identified mutations had potential implications for therapy in 20% (5) of the patients with genetic testing. Variants of unknown significance (VUS) were identified in 40% (6) of the tested patients. Disease causing mutations that were not suspected based on the patient's phenotype thereby representing novel presentations of previously described epilepsy syndromes were found in 12% (3 patients).Conclusions: In our clinical experience (1) genetic testing had a high yield of results relevant to diagnosis and therapy, (2) generalized epilepsy and epileptic encephalopathy were predictive of an even higher yield, (3) clinics offering genetic testing must be prepared to address the questions raised by the high frequency of VUS.