TY - JOUR T1 - Diagnostic Yield and Treatment Impact of Targeted Exome Sequencing in Early-onset Epilepsy JF - bioRxiv DO - 10.1101/139329 SP - 139329 AU - Michelle Demos AU - Ilaria Guella AU - Marna B. McKenzie AU - Sarah E. Buerki AU - Daniel M. Evans AU - Eric B. Toyota AU - Cyrus Boelman AU - Linda L. Huh AU - Anita Datta AU - Aspasia Michoulas AU - Kathryn Selby AU - Bruce H. Bjornson AU - Gabriella Horvath AU - Elena Lopez-Rangel AU - Clara DM van Karnebeek AU - Ramona Salvarinova AU - Erin Slade AU - Patrice Eydoux AU - Shelin Adam AU - Margot. I. Van Allen AU - Tanya N. Nelson AU - Corneliu Bolbocean AU - Mary B. Connolly AU - Matthew J. Farrer Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/05/17/139329.abstract N2 - Background To examine the impact on diagnosis, treatment and cost with early use of targeted whole-exome sequencing (WES) in early-onset epilepsy.Methods WES was performed on 50 patients with early-onset epilepsy (≤ 5 years) of unknown cause. Patients were classified as retrospective (epilepsy diagnosis > 6 months) or prospective (epilepsy diagnosis < 6 months). WES was performed on an Ion ProtonTM and variant reporting was restricted to the sequences of 565 known epilepsy genes. Diagnostic yield and time to diagnosis were calculated. An analysis of cost and impact on treatment was also performed.Results A likely/definite diagnosis was made in 17/50 patients (34%) with immediate treatment implications in 8/17 (47%). A possible diagnosis was identified in 9 additional patients (18%) for whom supporting evidence is pending. Time from epilepsy onset to genetic diagnosis was faster when WES was performed early in the diagnostic process (mean: 143 days prospective versus 2,172 days retrospective). Costs of prior negative tests averaged $8,344 in the retrospective group, suggesting savings of up to $5,110 per patient.Interpretation These results support the clinical utility and potential cost-effectiveness of using targeted WES early in the diagnostic workup of patients with unexplained early-onset epilepsy. The costs and clinical benefits are likely to continue to improve. Advances in precision medicine and further studies regarding impact on long-term clinical outcome will be important. ER -