Evidence-based consensus guidelines for ALS genetic testing and counseling

Ann Clin Transl Neurol. 2023 Nov;10(11):2074-2091. doi: 10.1002/acn3.51895. Epub 2023 Sep 10.


Objective: Advances in amyotrophic lateral sclerosis (ALS) gene discovery, ongoing gene therapy trials, and patient demand have driven increased use of ALS genetic testing. Despite this progress, the offer of genetic testing to persons with ALS is not yet "standard of care." Our primary goal is to develop clinical 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.

Methods: Core clinical questions were identified and a rapid review performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) 2015 method. Guideline recommendations were drafted and the strength of evidence for each recommendation was assessed by combining two systems: the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) System and the Evaluation of Genomic Applications in Practice and Prevention (EGAPP). A modified Delphi approach was used to reach consensus among a group of content experts for each guideline statement.

Results: A total of 35 guideline statements were developed. In summary, 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. The key education and genetic risk assessments that should be provided before and after testing are delineated. Specific guidance regarding testing methods and reporting for C9orf72 and other genes is provided for commercial laboratories.

Interpretation: These evidence-based, consensus guidelines will support all stakeholders in the ALS community in navigating benefits and challenges of genetic testing.

MeSH terms

  • Amyotrophic Lateral Sclerosis* / diagnosis
  • Amyotrophic Lateral Sclerosis* / genetics
  • Amyotrophic Lateral Sclerosis* / therapy
  • C9orf72 Protein / genetics
  • Counseling
  • Genetic Testing
  • Humans
  • Meta-Analysis as Topic
  • Systematic Reviews as Topic


  • C9orf72 Protein

Grants and funding

This work was funded by ALS Association .