Abstracts

Rationale: Epilepsy affects around 4.3 millions adults in the United States alone. In two-third of the cases, the cause of epilepsy is unknown. Investigations of suspected genetic etiology can often improve diagnostic precision, aid in prognostication, family counseling, and in special cases, it may even guide therapeutic decisions. The process of molecular analysis is complex and many eligible patients do not complete this diagnostic path. Baylor Genetic Epilepsy Clinic was established in order to facilitate access to genetic testing in adults with clinically defined epilepsy. We analyzed our patient cohort referred to date in order to better understand the clinical utility of the genetic testing in adults with epilepsy as well as potential barriers to completion of the testing process. Methods: We performed a retrospective chart review of 94 adults with epilepsy referred to Baylor Genetic Epilepsy Clinic between 2013 and 2016. Epilepsy phenotype and co-morbidities were defined according to the established guidelines. Testing platforms were tailored to epilepsy phenotypes and accepted practice recommendation. Genetic testing results were available in 34/94 patients and we analyzed their characteristics as well the reasons behind the absence of diagnostic data in the remainder of the cohort. Results: The epilepsy was primary generalized in 56/94 patients and localization-related in 38 cases. Epilepsy was refractory to treatment in 73%. Comorbid intellectual disability was present in 37% cases. The diagnostic process was complete in 34/94 individuals and sample submission was pending on six cases. Genetic testing yielded clinically pertinent results in 47% and biologically plausible findings in additional 12%. Whole exome sequencing provided explanation in 12/26 cases while chromosomal microarray was positive in 6/22 patients. Single gene testing confirmed suspected clinical diagnosis in 3 cases that included Dravet syndrome, Angelman syndrome, and familial cavernous malformations. Mitochondrial gene testing uncovered variants of uncertain clinical relevance in 3/22 cases. Since 60% of referred cases did not complete the diagnostic process, we analyzed the obstacles preventing the completion of the genetic testing. We found that financial or health insurance considerations closely followed by outstanding questions or concerns related to genetic screening figured most prominently as the cause for delay in testing and were operative in 52% and 38% of patients, respectively. Conclusions: In adults with epilepsy of suspected genetic etiology, genetic testing can provide meaningful results in close to 2/3 of the cases and a well defined syndromic classification tends to improve the testing yield. Yet, a considerable portion of adults with epilepsy does not complete the diagnostic process, mostly due to financial considerations, insurance denials and personal reservations related to genetic investigations. Our pilot findings warrant ongoing systematic analysis of patients and their social, cultural, and other personal circumstances. Funding: No funding was received to support this abstract