Medical Student Epilepsy Genetics Program, Krembil Neuroscience Centre, Toronto Western Hospital, University of Toronto Toronto, Ontario, Canada
Rationale: In a heterogenous condition such as epilepsy, wherein comorbidities muddle the phenotypic and genotypic landscape, a variety of genetic testing strategies need to be employed. However, it is unclear which tests have the largest diagnostic yield and reduce the time between clinical diagnosis and genotypic confirmation. We examined a large patient population with previous genetic testing to determine which type of genetic test provided the most positive results. Methods: We analyzed the clinical genetic testing of patients from the adult epilepsy clinic at Toronto Western Hospital in Toronto, Canada. To qualify, the patients had to have had at least one baseline microarray or karyotype and any other testing (small gene panel, large gene panel or whole exome sequencing [WES]). We quantified each test type and described testing outcomes, such as diagnostic yield. In the subgroup analysis, comorbidities were examined to see if they confounded the genotypic diagnostic yield. Results: Two hundred forty-three patients had 602 genetic tests ordered. The diagnostic yield for WES was 24%, while microarrays only had a true positive 8.3% of the time. Single gene panels were positive 9% of the time, and full gene panels showed a positive 25.5% of the time. Patients with a family history were more likely to have a positive result across all tests other than single gene panels. Patients with autism were more likely to have a negative test on the smaller panels and microarrays and more likely to get a result on the large panels and WES. Conclusions: Smaller test panels and microarrays had a low diagnostic yield and increased the time between initial genetic investigation and genetic diagnosis. Larger panels and whole exome sequencing are vastly more effective testing strategies, particularly for individuals with comorbidities. Funding: Please list any funding that was received in support of this abstract.: Funding in support of this abstract was received from EpLink and Ontario Brain Institute.
