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

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

doi:10.1001/jamaneurol.2022.3651

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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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..

Original language	English (US)
Pages (from-to)	1267-1276
Number of pages	10
Journal	JAMA Neurology
Volume	79
Issue number	12
DOIs	https://doi.org/10.1001/jamaneurol.2022.3651
State	Published - Dec 12 2022

ASJC Scopus subject areas

Clinical Neurology

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10.1001/jamaneurol.2022.3651

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McKnight, D., Morales, A., Hatchell, K. E., Bristow, S. L., Bonkowsky, J. L., Perry, M. S., Berg, A. T., Borlot, F., Esplin, E. D., Moretz, C., Angione, K., Ríos-Pohl, L., Nussbaum, R. L., Aradhya, S., Haldeman-Englert, C. R., Levy, R. J., Parachuri, V. G., Lay-Son, G., De Montellano, D. J. D. O., ... Pavliuk, M. (2022). Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice. JAMA Neurology, 79(12), 1267-1276. https://doi.org/10.1001/jamaneurol.2022.3651

McKnight, D, Morales, A, Hatchell, KE, Bristow, SL, Bonkowsky, JL, Perry, MS, Berg, AT, Borlot, F, Esplin, ED, Moretz, C, Angione, K, Ríos-Pohl, L, Nussbaum, RL, Aradhya, S, Haldeman-Englert, CR, Levy, RJ, Parachuri, VG, Lay-Son, G, De Montellano, DJDO, Ramirez-Garcia, MA, Benítez Alonso, EO, Ziobro, J, Chirita-Emandi, A, Felix, TM, Kulasa-Luke, D, Megarbane, A, Karkare, S, Chagnon, SL, Humberson, JB, Assaf, MJ, Silva, S, Zarroli, K, Boyarchuk, O, Nelson, GR, Palmquist, R, Hammond, KC, Hwang, ST, Boutlier, SB, Nolan, M, Batley, KY, Chavda, D, Reyes-Silva, CA, Miroshnikov, O, Zuccarelli, B, Amlie-Wolf, L, Wheless, JW, Seinfeld, S, Kanhangad, M, Freeman, JL, Monroy-Santoyo, S, Rodriguez-Vazquez, N, Ryan, MM, MacHie, M, Guerra, P, Hassan, MJ, Candee, MS, Bupp, CP, Park, KL, Muller, E, Lupo, P, Pedersen, RC, Arain, AM, Murphy, A, Schatz, K, Mu, W, Kalika, PM, Plaza, L, Kellogg, MA, Lora, EG, Carson, RP, Svystilnyk, V, Venegas, V, Luke, RR, Jiang, H, Stetsenko, T, Dueñas-Roque, MM, Trasmonte, J, Burke, RJ, Hurst, ACE, Smith, DM, Massingham, LJ, Pisani, L, Costin, CE, Ostrander, B, Filloux, FM, Ananth, AL, Mohamed, IS, Nechai, A, Dao, JM, Fahey, MC, Aliu, E, Falchek, S, Press, CA, Treat, L, Eschbach, K, Starks, A, Kammeyer, R, Bear, JJ, Jacobson, M, Chernuha, V, Meibos, B, Wong, K, Sweney, MT, Espinoza, AC, Van Orman, CB, Weinstock, A, Kumar, A, Soler-Alfonso, C, Nolan, DA, Raza, M, Rojas Carrion, MD, Chari, G, Marsh, ED, Shiloh-Malawsky, Y, Parikh, S, Gonzalez-Giraldo, E, Fulton, S, Sogawa, Y, Burns, K, Malets, M, Montiel Blanco, JD, Habela, CW, Wilson, CA, Guzmán, GG & Pavliuk, M 2022, 'Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice', JAMA Neurology, vol. 79, no. 12, pp. 1267-1276. https://doi.org/10.1001/jamaneurol.2022.3651

@article{cbad8d733b6f4740b8e07f1f55fc0d84,

title = "Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice",

abstract = "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..",

author = "Dianalee McKnight and Ana Morales and Hatchell, {Kathryn E.} and Bristow, {Sara L.} and Bonkowsky, {Joshua L.} and Perry, {Michael Scott} and Berg, {Anne T.} and Felippe Borlot and Esplin, {Edward D.} and Chad Moretz and Katie Angione and Loreto R{\'i}os-Pohl and Nussbaum, {Robert L.} and Swaroop Aradhya and Haldeman-Englert, {Chad R.} and Levy, {Rebecca J.} and Parachuri, {Venu G.} and Guillermo Lay-Son and {De Montellano}, {David J.D{\'a}vila Ortiz} and Ramirez-Garcia, {Miguel Angel} and {Ben{\'i}tez Alonso}, {Edmar O.} and Julie Ziobro and Adela Chirita-Emandi and Felix, {Temis M.} and Dianne Kulasa-Luke and Andre Megarbane and Shefali Karkare and Chagnon, {Sarah L.} and Humberson, {Jennifer B.} and Assaf, {Melissa J.} and Sebastian Silva and Katherine Zarroli and Oksana Boyarchuk and Nelson, {Gary R.} and Rachel Palmquist and Hammond, {Katherine C.} and Hwang, {Sean T.} and Boutlier, {Susan B.} and Melinda Nolan and Batley, {Kaitlin Y.} and Devraj Chavda and Reyes-Silva, {Carlos Alberto} and Oleksandr Miroshnikov and Britton Zuccarelli and Louise Amlie-Wolf and Wheless, {James W.} and Syndi Seinfeld and Manoj Kanhangad and Freeman, {Jeremy L.} and Susana Monroy-Santoyo and Natalia Rodriguez-Vazquez and Ryan, {Monique M.} and Michelle MacHie and Patricio Guerra and Hassan, {Muhammad Jawad} and Candee, {Meghan S.} and Bupp, {Caleb P.} and Park, {Kristen L.} and Eric Muller and Pamela Lupo and Pedersen, {Robert C.} and Arain, {Amir M.} and Andrea Murphy and Krista Schatz and Weiyi Mu and Kalika, {Paige M.} and Lautaro Plaza and Kellogg, {Marissa A.} and Lora, {Evelyn G.} and Carson, {Robert P.} and Victoria Svystilnyk and Viviana Venegas and Luke, {Rebecca R.} and Huiyuan Jiang and Tetiana Stetsenko and Due{\~n}as-Roque, {Milagros M.} and Joseph Trasmonte and Burke, {Rebecca J.} and Hurst, {Anna C.E.} and Smith, {Douglas M.} and Massingham, {Lauren J.} and Laura Pisani and Costin, {Carrie E.} and Betsy Ostrander and Filloux, {Francis M.} and Ananth, {Amitha L.} and Mohamed, {Ismail S.} and Alla Nechai and Dao, {Jasmin M.} and Fahey, {Michael C.} and Ermal Aliu and Stephen Falchek and Press, {Craig A.} and Lauren Treat and Krista Eschbach and Angela Starks and Ryan Kammeyer and Bear, {Joshua J.} and Mona Jacobson and Veronika Chernuha and Bailey Meibos and Kristen Wong and Sweney, {Matthew T.} and Espinoza, {A. Chris} and {Van Orman}, {Colin B.} and Arie Weinstock and Ashutosh Kumar and Claudia Soler-Alfonso and Nolan, {Danielle A.} and Muhammad Raza and {Rojas Carrion}, {Miguel David} and Geetha Chari and Marsh, {Eric D.} and Yael Shiloh-Malawsky and Sumit Parikh and Ernesto Gonzalez-Giraldo and Stephen Fulton and Yoshimi Sogawa and Kaitlyn Burns and Myroslava Malets and {Montiel Blanco}, {Johnny David} and Habela, {Christa W.} and Wilson, {Carey A.} and Guzm{\'a}n, {Guillermo G.} and Mariia Pavliuk",

year = "2022",

month = dec,

day = "12",

doi = "10.1001/jamaneurol.2022.3651",

language = "English (US)",

volume = "79",

pages = "1267--1276",

journal = "JAMA Neurology",

issn = "2168-6149",

publisher = "American Medical Association",

number = "12",

}

TY - JOUR

T1 - Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

AU - McKnight, Dianalee

AU - Morales, Ana

AU - Hatchell, Kathryn E.

AU - Bristow, Sara L.

AU - Bonkowsky, Joshua L.

AU - Perry, Michael Scott

AU - Berg, Anne T.

AU - Borlot, Felippe

AU - Esplin, Edward D.

AU - Moretz, Chad

AU - Angione, Katie

AU - Ríos-Pohl, Loreto

AU - Nussbaum, Robert L.

AU - Aradhya, Swaroop

AU - Haldeman-Englert, Chad R.

AU - Levy, Rebecca J.

AU - Parachuri, Venu G.

AU - Lay-Son, Guillermo

AU - De Montellano, David J.Dávila Ortiz

AU - Ramirez-Garcia, Miguel Angel

AU - Benítez Alonso, Edmar O.

AU - Ziobro, Julie

AU - Chirita-Emandi, Adela

AU - Felix, Temis M.

AU - Kulasa-Luke, Dianne

AU - Megarbane, Andre

AU - Karkare, Shefali

AU - Chagnon, Sarah L.

AU - Humberson, Jennifer B.

AU - Assaf, Melissa J.

AU - Silva, Sebastian

AU - Zarroli, Katherine

AU - Boyarchuk, Oksana

AU - Nelson, Gary R.

AU - Palmquist, Rachel

AU - Hammond, Katherine C.

AU - Hwang, Sean T.

AU - Boutlier, Susan B.

AU - Nolan, Melinda

AU - Batley, Kaitlin Y.

AU - Chavda, Devraj

AU - Reyes-Silva, Carlos Alberto

AU - Miroshnikov, Oleksandr

AU - Zuccarelli, Britton

AU - Amlie-Wolf, Louise

AU - Wheless, James W.

AU - Seinfeld, Syndi

AU - Kanhangad, Manoj

AU - Freeman, Jeremy L.

AU - Monroy-Santoyo, Susana

AU - Rodriguez-Vazquez, Natalia

AU - Ryan, Monique M.

AU - MacHie, Michelle

AU - Guerra, Patricio

AU - Hassan, Muhammad Jawad

AU - Candee, Meghan S.

AU - Bupp, Caleb P.

AU - Park, Kristen L.

AU - Muller, Eric

AU - Lupo, Pamela

AU - Pedersen, Robert C.

AU - Arain, Amir M.

AU - Murphy, Andrea

AU - Schatz, Krista

AU - Mu, Weiyi

AU - Kalika, Paige M.

AU - Plaza, Lautaro

AU - Kellogg, Marissa A.

AU - Lora, Evelyn G.

AU - Carson, Robert P.

AU - Svystilnyk, Victoria

AU - Venegas, Viviana

AU - Luke, Rebecca R.

AU - Jiang, Huiyuan

AU - Stetsenko, Tetiana

AU - Dueñas-Roque, Milagros M.

AU - Trasmonte, Joseph

AU - Burke, Rebecca J.

AU - Hurst, Anna C.E.

AU - Smith, Douglas M.

AU - Massingham, Lauren J.

AU - Pisani, Laura

AU - Costin, Carrie E.

AU - Ostrander, Betsy

AU - Filloux, Francis M.

AU - Ananth, Amitha L.

AU - Mohamed, Ismail S.

AU - Nechai, Alla

AU - Dao, Jasmin M.

AU - Fahey, Michael C.

AU - Aliu, Ermal

AU - Falchek, Stephen

AU - Press, Craig A.

AU - Treat, Lauren

AU - Eschbach, Krista

AU - Starks, Angela

AU - Kammeyer, Ryan

AU - Bear, Joshua J.

AU - Jacobson, Mona

AU - Chernuha, Veronika

AU - Meibos, Bailey

AU - Wong, Kristen

AU - Sweney, Matthew T.

AU - Espinoza, A. Chris

AU - Van Orman, Colin B.

AU - Weinstock, Arie

AU - Kumar, Ashutosh

AU - Soler-Alfonso, Claudia

AU - Nolan, Danielle A.

AU - Raza, Muhammad

AU - Rojas Carrion, Miguel David

AU - Chari, Geetha

AU - Marsh, Eric D.

AU - Shiloh-Malawsky, Yael

AU - Parikh, Sumit

AU - Gonzalez-Giraldo, Ernesto

AU - Fulton, Stephen

AU - Sogawa, Yoshimi

AU - Burns, Kaitlyn

AU - Malets, Myroslava

AU - Montiel Blanco, Johnny David

AU - Habela, Christa W.

AU - Wilson, Carey A.

AU - Guzmán, Guillermo G.

AU - Pavliuk, Mariia

PY - 2022/12/12

Y1 - 2022/12/12

N2 - 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..

AB - 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..

UR - http://www.scopus.com/inward/record.url?scp=85144008923&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85144008923&partnerID=8YFLogxK

U2 - 10.1001/jamaneurol.2022.3651

DO - 10.1001/jamaneurol.2022.3651

M3 - Article

C2 - 36315135

AN - SCOPUS:85144008923

SN - 2168-6149

VL - 79

SP - 1267

EP - 1276

JO - JAMA Neurology

JF - JAMA Neurology

IS - 12

ER -

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

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