Evidence-based, consensus guidelines for genetic testing and counseling for patients with amyotrophic lateral sclerosis (ALS) have been created. The 35 guideline statements are published in Annals of Clinical and Translational Neurology and include the new recommendation that all persons with ALS be offered comprehensive genetic testing. This, the authors said, will facilitate access to gene-targeted therapies.
The guidelines, which can be adopted by any provider, recommend all persons with ALS should be offered single-step genetic testing, consisting of a C9orf72 assay, along with sequencing of SOD1, FUS, and TARDBP, at a minimum.
Researchers at the Ohio State University Wexner Medical Center and College of Medicine led the creation of the guidelines, which aim to provide clinicians with a framework for genetic testing and outline the information that should be provided to patients before and after testing. In addition, the guidelines provide specific recommendations regarding test methods and reporting, thus providing guidance to both clinicians and testing laboratories.
ALS—also known as Lou Gehrig’s disease for the famous baseball who was forced to retire in 1939 because of the incurable neuromuscular disorder—affects more than 31,000 people in the United States, according to the Centers for Disease Control and Prevention.
Advances in ALS gene discovery, ongoing gene therapy trials, and patient demand have driven increased use of ALS genetic testing, which is rapidly advancing. Recently, a team at the Translational Genomics Research Institute, or TGen, identified a repetitive expansion in the C9ORF72 gene, which is common to both ALS and frontotemporal dementia.
“Despite this progress, the offer of genetic testing to persons with ALS is not yet ‘standard of care’ and many people who desire access to genetic testing are not offered it. We developed ALS genetic counseling and testing guidelines to improve and standardize genetic counseling and testing practice among neurologists, genetic counselors, or any provider caring for persons with ALS,” said corresponding author Jennifer Roggenbuck, MS, CGC, a licensed genetic counselor and associate professor in the division of human genetics in the department of internal medicine at the Ohio State Wexner Medical Center.
Guideline recommendations were drafted and the strength of evidence for each recommendation was assessed to reach consensus among a group of content experts for each guideline statement.
“Rapid progress in the discovery of ALS-associated genes, and a growing recognition of the genetic basis of clinically sporadic ALS, has opened the door to an era of gene-targeted therapies for persons with ALS. These evidence-based, consensus guidelines will support all stakeholders in the ALS community in navigating the benefits and challenges of genetic testing,” said co-author Stephen Kolb, MD, PhD, professor of neurology and biological chemistry and pharmacology at the Ohio State University College of Medicine.
“These guidelines reflect current genomic technology, which will evolve along with our scientific understanding of the genetics of ALS. It is expected that genetic associations with ALS and related disorders will continue to expand, and with it, the complexity of results that must be communicated,” Roggenbuck said.
She added, “We view these guidelines as a first step toward a uniform and equitable approach to ALS genetic testing that will require revision periodically as new genetic discoveries and new genetic therapies move forward for people living with ALS.”
