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Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

2022; American Medical Association; Volume: 79; Issue: 12 Linguagem: Inglês

10.1001/jamaneurol.2022.3651

2168-6157

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

Epilepsy research and treatment

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.