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

Importance

It 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.

Objective

To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.

Design, Setting, and Participants

This 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.

Exposures

Genetic test results.

Main Outcomes and Measures

Clinical 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.

Results

Among 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 Relevance

Results 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.