Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice
Journal
JAMA Neurology
ISSN
2168-6149
Date Issued
2022
Author(s)
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
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:sec id="ab-noi220068-4"><jats:title>Importance</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-noi220068-5"><jats:title>Objective</jats:title><jats:p>To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.</jats:p></jats:sec><jats:sec id="ab-noi220068-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-noi220068-7"><jats:title>Exposures</jats:title><jats:p>Genetic test results.</jats:p></jats:sec><jats:sec id="ab-noi220068-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-noi220068-9"><jats:title>Results</jats:title><jats:p>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%).</jats:p></jats:sec><jats:sec id="ab-noi220068-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>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.</jats:p></jats:sec>
Cite this document
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., ELEVIATE Consortium, Haldeman-Englert, C. R., Levy, R. J., Parachuri, V. G., Lay-Son, G., … Pavliuk, M. (2022). Genetic testing to inform epilepsy treatment management from an international study of clinical practice. JAMA Neurology, 79(12), 1267. https://doi.org/10.1001/jamaneurol.2022.3651
Subjects
adolescent
;
adult
;
child
;
child, preschool
;
cross-sectional studies
;
epilepsy
;
female
;
genetic testing
;
humans
;
infant
;
infant, newborn
;
male
;
middle aged
;
retrospective studies
;
seizures
;
young adult
;
adult
;
adverse event
;
alertness
;
article
;
autosomal recessive disorder
;
child
;
clinical decision making
;
clinical outcome
;
clinical practice
;
clinician
;
cross-sectional study
;
depdc5 gene
;
epilepsy
;
female
;
follow up
;
gene
;
genetic screening
;
health care personnel
;
health insurance
;
human
;
intellectual impairment
;
kcnq2 gene
;
major clinical study
;
male
;
mecp2 gene
;
morbidity
;
multigene family
;
newborn
;
pcdh19 gene
;
prrt2 gene
;
retrospective study
;
scn1a gene
;
single nucleotide polymorphism
;
stxbp1 gene
;
treatment outcome
;
x chromosome linked disorder
;
adolescent
;
epilepsy
;
genetics
;
infant
;
middle aged
;
preschool child
;
procedures
;
seizure
;
young adult