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.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.