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, 2nd; 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; ELEVIATE Consortium

doi:10.1001/jamaneurol.2022.3651

Back

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

Journal article

Open access

Peer reviewed

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, …

JAMA neurology, Vol.79(12), pp.1267-1276

2022-12-01

DOI: https://doi.org/10.1001/jamaneurol.2022.3651

PMID: 36315135

Appears in Miller School of Medicine - Latest Publications

Abstract

Adolescent

Adult

Child

Child, Preschool

Cross-Sectional Studies

Epilepsy - drug therapy

Epilepsy - genetics

Female

Genetic Testing - methods

Humans

Infant

Infant, Newborn

Male

Middle Aged

Retrospective Studies

Seizures - genetics

Young Adult

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. To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. 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. Genetic test results. 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. 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%). 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.

Files and links (1)

url

https://doi.org/10.1001/jamaneurol.2022.3651View

Published (Version of record) Open

Metrics

4 Record Views

6 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.222 Epilepsy & Seizures; 1.222.143 Epilepsy
Web Of Science research areas: Clinical Neurology
ESI research areas: Neuroscience & Behavior

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice
Creators: Dianalee McKnight - Invitae
Ana Morales - Invitae
Kathryn E Hatchell - Invitae
Sara L Bristow - Invitae
Joshua L Bonkowsky - University of Utah
Michael Scott Perry - Cook Children's Medical Center
Anne T Berg - Northwestern University
Felippe Borlot - University of Manitoba
Edward D Esplin - Invitae
Chad Moretz - Invitae
Katie Angione - Children's Hospital Colorado
Loreto Ríos-Pohl - Finis Terrae University
Robert L Nussbaum - Invitae
Swaroop Aradhya - Invitae
Chad R Haldeman-Englert - Mission Health
Rebecca J Levy - Lucile Packard Children's Hospital
Venu G Parachuri - Kaiser Permanente Center for Health Research
Guillermo Lay-Son - Pontificia Universidad Católica de Chile
David J Dávila-Ortiz de Montellano - Instituto Nacional de Neurología y Neurocirugía
Miguel Angel Ramirez-Garcia - Instituto Nacional de Neurología y Neurocirugía
Edmar O Benítez Alonso - National Institute of Neurology
Julie Ziobro - University of Michigan–Ann Arbor
Adela Chirita-Emandi - Victor Babeș University of Medicine and Pharmacy Timișoara
Temis M Felix - Hospital de Clínicas de Porto Alegre
Dianne Kulasa-Luke - Akron Children's Hospital
Andre Megarbane - Lebanese American University
Shefali Karkare - Cohen Children's Medical Center
Sarah L Chagnon - Children's Hospital of The King's Daughters
Jennifer B Humberson - University of Virginia
Melissa J Assaf - Banner Thunderbird Medical Center
Sebastian Silva - Child Neurology Service, Hospital de Puerto Montt, Puerto Montt, Chile.
Katherine Zarroli - Jacksonville University
Oksana Boyarchuk - I.Horbachevsky Ternopil National Medical University
Gary R Nelson - University of Utah
Rachel Palmquist - University of Utah
Katherine C Hammond - University of Alabama at Birmingham
Sean T Hwang - Hofstra University
Susan B Boutlier - ECU Physician Internal Medicine Pediatric Neurology, Greenville, North Carolina.
Melinda Nolan - Starship Children's Health
Kaitlin Y Batley - Southwestern Medical Center
Devraj Chavda - SUNY Downstate Medical Center
Carlos Alberto Reyes-Silva - Universidad de los Hemisferios
Oleksandr Miroshnikov - Institute of Pediatrics, Obstetrics, and Gynecology named after acad. O.M. Lukyanova of the National Academy of Medical Sciences of Ukraine
Britton Zuccarelli - Kansas State University Salina Aerospace and Technology Campus
Louise Amlie-Wolf - Nemours Children's Hospital, Wilmington, Delaware.
James W Wheless - University of Tennessee Health Science Center
Syndi Seinfeld - Joe DiMaggio Children's Hospital
Manoj Kanhangad - Monash University
Jeremy L Freeman - Royal Children's Hospital
Susana Monroy-Santoyo - Instituto Nacional de Pediatria
Natalia Rodriguez-Vazquez - University of Puerto Rico, Medical Sciences Campus
Monique M Ryan - Royal Children's Hospital
Michelle Machie - Southwestern Medical Center
Patricio Guerra - San Sebastián University
Muhammad Jawad Hassan - National University of Medical Sciences
Meghan S Candee - University of Utah
Caleb P Bupp - Helen DeVos Children's Hospital
Kristen L Park - Children's Hospital Colorado
Eric Muller, 2nd - Clinical Genetics, Stanford Children's Health Specialty Services, San Francisco, California
Pamela Lupo - Clear Creek Independent School District
Robert C Pedersen - Hawaii Permanente Medical Group
Amir M Arain - University of Utah
Andrea Murphy - Mary Bird Perkins Cancer Center
Krista Schatz - Johns Hopkins University
Weiyi Mu - Johns Hopkins University
Paige M Kalika - University of Miami
Lautaro Plaza - Maternal Perinatal Hospital Mónica Pretelini
Marissa A Kellogg - Oregon Health & Science University
Evelyn G Lora - Dominican Neurological and Neurosurgical Society, Santo Domingo, Dominican Republic.
Robert P Carson - Vanderbilt University Medical Center
Victoria Svystilnyk - Shupyk National Healthcare University of Ukraine
Viviana Venegas - Universidad del Desarrollo
Rebecca R Luke - Cook Children's Medical Center
Huiyuan Jiang - Nationwide Children's Hospital
Tetiana Stetsenko - Brain Stimulation Center, Kyiv, Ukraine.
Milagros M Dueñas-Roque - Hospital Nacional Cayetano Heredia
Joseph Trasmonte - Navicent Health
Rebecca J Burke - West Virginia University
Anna C E Hurst - University of Alabama at Birmingham
Douglas M Smith - Minnesota Epilepsy Group
Lauren J Massingham - Providence College
Laura Pisani - Hofstra University
Carrie E Costin - Akron Children's Hospital
Betsy Ostrander - University of Utah
Francis M Filloux - University of Utah
Amitha L Ananth - University of Alabama at Birmingham
Ismail S Mohamed - University of Alabama at Birmingham
Alla Nechai - Kyiv City Clinical Oncology Center
Jasmin M Dao - Child Neurology Associates
Michael C Fahey - Monash University
Ermal Aliu - Penn State Milton S. Hershey Medical Center
Stephen Falchek - Thomas Jefferson University
Craig A Press - Children's Hospital Colorado
Lauren Treat - Children's Hospital Colorado
Krista Eschbach - Children's Hospital Colorado
Angela Starks - Children's Hospital Colorado
Ryan Kammeyer - Children's Hospital Colorado
Joshua J Bear - Children's Hospital Colorado
Mona Jacobson - Children's Hospital Colorado
Veronika Chernuha - Tel Aviv Sourasky Medical Center
Bailey Meibos - University of Utah
Kristen Wong - University of Utah
Matthew T Sweney - University of Utah
A Chris Espinoza - University of Utah
Colin B Van Orman - University of Utah
Arie Weinstock - University at Buffalo, State University of New York
Ashutosh Kumar - Penn State Milton S. Hershey Medical Center
Claudia Soler-Alfonso - Baylor College of Medicine
Danielle A Nolan - Corewell Health Children's
Muhammad Raza - Nishtar Medical College and Hospital
Miguel David Rojas Carrion - Alejandro Mann Hospital Complex, Guayaquil, Ecuador
Geetha Chari - SUNY Downstate Medical Center
Eric D Marsh - Children's Hospital of Philadelphia
Yael Shiloh-Malawsky - University of North Carolina at Chapel Hill
Sumit Parikh - Cleveland Clinic
Ernesto Gonzalez-Giraldo - University of California, San Francisco
Stephen Fulton - University of Tennessee Health Science Center
Yoshimi Sogawa - Children's Hospital of Pittsburgh
Kaitlyn Burns - Sanford Health
Myroslava Malets - Uzhhorod National University
Johnny David Montiel Blanco - National Institute of Child Health, Lima, Perú
Christa W Habela - Johns Hopkins University
Carey A Wilson - University of Utah
Guillermo G Guzmán - Hospital San Borja Arriarán
Mariia Pavliuk - Volyn Regional Hospital, Lutsk, Ukraine.
ELEVIATE Consortium
Publication Details: JAMA neurology, Vol.79(12), pp.1267-1276
Academic Unit: Miller School of Medicine; UMMG Department of Neurology
Language: English
Resource Type: Journal article
PMID: 36315135
Record Identifier: 991031785521202976