Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice
Authors: McKnight Dianalee , Morales Ana , Hatchell Kathryn E. , Bristow Sara L. , Bonkowsky Joshua L. , Perry Michael Scott , Berg Anne T. , Borlot Felippe , Esplin Edward D. , Moretz Chad , Angione Katie , Ríos-Pohl Loreto , Nussbaum Robert L. , Aradhya Swaroop ,   ELEVIATE Consortium, Haldeman-Englert Chad R. , Levy Rebecca J. , Parachuri Venu G. , Lay-Son Guillermo , de Montellano David J. Dávila-Ortiz , Ramirez-Garcia Miguel Angel , Benítez Alonso Edmar O. , Ziobro Julie , Chirita-Emandi Adela , Felix Temis M. , Kulasa-Luke Dianne , Megarbane Andre , Karkare Shefali , Chagnon Sarah L. , Humberson Jennifer B. , Assaf Melissa J. , Silva Sebastian , Zarroli Katherine , Boyarchuk Oksana , Nelson Gary R. , Palmquist Rachel , Hammond Katherine C. , Hwang Sean T. , Boutlier Susan B. , Nolan Melinda , Batley Kaitlin Y. , Chavda Devraj , Reyes-Silva Carlos Alberto , Miroshnikov Oleksandr , Zuccarelli Britton , Amlie-Wolf Louise , Wheless James W. , Seinfeld Syndi , Kanhangad Manoj , Freeman Jeremy L. , Monroy-Santoyo Susana , Rodriguez-Vazquez Natalia , Ryan Monique M. , Machie Michelle , Guerra Patricio , Hassan Muhammad Jawad , Candee Meghan S. , Bupp Caleb P. , Park Kristen L. , Muller Eric , Lupo Pamela , Pedersen Robert C. , Arain Amir M. , Murphy Andrea , Schatz Krista , Mu Weiyi , Kalika Paige M. , Plaza Lautaro , Kellogg Marissa A. , Lora Evelyn G. , Carson Robert P. , Svystilnyk Victoria , Venegas Viviana , Luke Rebecca R. , Jiang Huiyuan , Stetsenko Tetiana , Dueñas-Roque Milagros M. , Trasmonte Joseph , Burke Rebecca J. , Hurst Anna C.E. , Smith Douglas M. , Massingham Lauren J. , Pisani Laura , Costin Carrie E. , Ostrander Betsy , Filloux Francis M. , Ananth Amitha L. , Mohamed Ismail S. , Nechai Alla , Dao Jasmin M. , Fahey Michael C. , Aliu Ermal , Falchek Stephen , Press Craig A. , Treat Lauren , Eschbach Krista , Starks Angela , Kammeyer Ryan , Bear Joshua J. , Jacobson Mona , Chernuha Veronika , Meibos Bailey , Wong Kristen , Sweney Matthew T. , Espinoza A. Chris , Van Orman Colin B. , Weinstock Arie , Kumar Ashutosh , Soler-Alfonso Claudia , Nolan Danielle A. , Raza Muhammad , Rojas Carrion Miguel David , Chari Geetha , Marsh Eric D. , Shiloh-Malawsky Yael , Parikh Sumit , Gonzalez-Giraldo Ernesto , Fulton Stephen , Sogawa Yoshimi , Burns Kaitlyn , Malets Myroslava , Montiel Blanco Johnny David , Habela Christa W. , Wilson Carey A. , Guzmán Guillermo G. , Pavliuk Mariia 
Published: October 2022

ImportanceIt is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.ObjectiveTo evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.Design, Setting, and ParticipantsThis was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals.ExposuresGenetic test results.Main Outcomes and MeasuresClinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms.ResultsAmong 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%).Conclusions and RelevanceResults of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.