Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice
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  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.
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; 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.; and Pavliuk, Mariia, "Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice" (2022). Department of Pediatrics Faculty Papers. Paper 127.
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This article is the author's final published version in JAMA Neurology, Volume 79, Issue 12, December 2022, Pg. 1267 - 1276.
The published version is available at https://doi.org/10.1001/jamaneurol.2022.3651. Copyright © 2022 McKnight D et al. JAMA Neurology.