Presymptomatic ALS genetic counseling and testing
Experience and recommendations
Abstract
Remarkable advances in our understanding of the genetic contributions to amyotrophic lateral sclerosis (ALS) have sparked discussion and debate about whether clinical genetic testing should routinely be offered to patients with ALS. A related, but distinct, question is whether presymptomatic genetic testing should be offered to family members who may be at risk for developing ALS. Existing guidelines for presymptomatic counseling and testing are mostly based on small number of individuals, clinical judgment, and experience from other neurodegenerative disorders. Over the course of the last 8 years, we have provided testing and 317 genetic counseling sessions (including predecision, pretest, posttest, and ad hoc counseling) to 161 first-degree family members participating in the Pre-Symptomatic Familial ALS Study (Pre-fALS), as well as testing and 75 posttest counseling sessions to 63 individuals with familial ALS. Based on this experience, and the real-world challenges we have had to overcome in the process, we recommend an updated set of guidelines for providing presymptomatic genetic counseling and testing to people at high genetic risk for developing ALS. These recommendations are especially timely and relevant given the growing interest in studying presymptomatic ALS.
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Information & Authors
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Copyright
© 2016 American Academy of Neurology.
Publication History
Received: December 10, 2015
Accepted: March 15, 2016
Published online: May 18, 2016
Published in print: June 14, 2016
Disclosure
M. Benatar received research funding from MDA 4365 and 172123; ALSA 2015 and 16-TACL-242; NINDS U10NS077423, U54NS092091, U01NS084495, and R44NS070385; NIMH/NICHD/NINDS Brain and Tissue (NBTR) HHSN271201300028C; FDA R01FD003517 and R01FD003710; DOD AL120068; Cytokinetics Inc. CY4031; Alexion Pharmaceuticals ECU-MG-301 and 302; Kimmelman Estate, and ALS Recovery Fund. C. Stanislaw received research support from MDA 4365 and 172123, and ALSA 2015. E. Reyes received research support from ALSA 2015 and Alexion Pharmaceuticals ECU-MG-301 and 302. S. Hussain received research support from ALSA 2015 and NINDS U54NS092091. A. Cooley received research support from Alexion Pharmaceuticals ECU-MG-301 and 302, and ALS Recovery Fund. M.C. Fernandez received research support from ALS Recovery Fund. D.D. Dauphin received research support from ALSA 2015. S.C. Michon received research support from Kimmelman Estate. P.M. Andersen received research funding from Knut and Alice Wallenberg Foundation, Swedish Science Council, Ulla-Carin Lindquist Foundation, and Brain Research Foundation. J. Wuu received research support from MDA 4365 and 172123; NINDS U10NS077423 and U54NS092091; NIA P01AG14449; FDA R01FD003517; and DOD AL120068.
Study Funding
Muscular Dystrophy Association (MDA 4365 and MDA 172123), ALS Association (ALSA 2015), Kimmelman Estate, ALS Recovery Fund, Knut and Alice Wallenberg Foundation, Swedish Science Council, Ulla-Carin Lindquist Foundation, Brain Research Foundation.
Authors
Author Contributions
M. Benatar: study concept and design, study execution, genetic counseling, participant evaluation, manuscript writing, and critical revision. C. Stanislaw: genetic counseling, manuscript writing, and critical revision. E. Reyes: participant recruitment and evaluation. S. Hussain: participant recruitment and evaluation. A. Cooley: participant recruitment and evaluation. M.C. Fernandez: participant recruitment and evaluation. D.D. Dauphine: participant recruitment and evaluation. S.C. Michon: participant recruitment and evaluation. P.M. Andersen: genetic testing, critical review and editing of manuscript. J. Wuu: study concept and design, study execution, data management, manuscript writing, and critical revision.
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