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, Beaumont Health
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

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Publication Date


Publication Title

JAMA Neurology


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.


Online ahead of print.





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