The potential role of
genetic testing in
ALS

Genetic ALS / The potential role of genetic testing

5 min read

Breakthroughs in ALS research and advances in gene sequencing technology have helped establish the fact that patients with seemingly sporadic ALS (sALS), without any family history, may still carry genetic mutations for the disease.1 And yet, genetic testing remains largely absent from standard ALS diagnostic protocols.2 The El Escorial criteria contain limited information on when genetic testing should occur, and testing is often restricted to the confirmatory diagnoses of suspected familial ALS (fALS).2

Angela Genge, MD, Executive Director of the Clinical Research Unit at the Montreal Neurological Institute and Hospital, is one of the world’s foremost proponents of genetic testing for all patients with ALS, even those whose disease is seemingly sporadic.

“Emerging science shows that mutations in more than 25 different genes can play a role in ALS,” Dr. Genge says.3 “The reality is that even patients with seemingly sporadic ALS may still have a genetic component to their disease.”4

Assessing the genetic testing landscape

Genetic testing may be a necessary step to determine eligibility for clinical trials.1,3 Knowing that, Dr. Genge and a group of her colleagues from Canada and the United States set out to survey the current ALS genetic testing landscape in the United States.2

Dr. Genge and her team wanted to estimate the frequency with which seemingly sporadic cases of ALS were in fact caused by SOD1 and C9orf72 expansion mutations2—the 2 most common mutations among those living with genetic ALS.1 The idea was inspired by what she saw in the field.

“In clinics like mine and a number of other clinics around the world, we’ve seen patients whose disease was previously categorized as sALS,” Dr. Genge says. “But because we provide genetic testing to every patient who consents, we have been able to identify a number of individuals who have a genetic form of ALS even without a known family history.”

Genetic tests and DNA’s structure
Genetic tests and DNA’s structure

Dr. Genge and her team examined data on ALS genetic testing within the United States, collected through public domains and private resources, as well as information from nearly 40 laboratories that provide genetic testing to patients with ALS.2

The team then conducted a review and meta-analysis of data on the frequencies of SOD1 and C9orf72 repeat expansion mutations in populations of European descent. Next, they compared these estimated numbers with data from large population-based studies that reported on genetic testing or case series between 2010 and 2020.2

When the analysis was done, Dr. Genge and her team found themselves with yet more evidence to support genetic testing in all patients with ALS.2

In addition to findings regarding genetic testing, the team identified what appeared to be shortcomings in some ALS genotyping practices particularly the reliance on family history to determine a patient’s fALS or sALS status. Through their research, Dr. Genge and her team found there were disparities in the very definition of “familial,” with some clinicians defining it as a case in which a first-degree relative also has ALS and others expanding the definition to include extended family. In either case, the team noted that difficulty in obtaining a complete family history—whether due to small family size or incomplete penetrance—was also an issue for clinicians.2

Given their findings, Dr. Genge and her team made a determination: routine genetic testing should be a consideration not just for patients with a family history of ALS, but for all patients living with this disease.2

Potential risks of genetic testing

While the physical risks associated with genetic testing may be minimal, there can be emotional, social, or financial consequences of obtaining a genetic test. The possibility of genetic discrimination in employment, as well as for disability or life insurance, can also be a concern for patients. 

For these reasons, your patients should speak with a genetic counselor before, during, and after receiving genetic testing results. A genetic counselor can further explain in detail the benefits, risks, and limitations of the genetic testing to your patients.

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Read about supporting
patients living with ALS
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Read about developments
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References: 1. Roggenbuck J, Quick A, Kolb SJ. Genetic testing and genetic counseling for amyotrophic lateral sclerosis: an update for clinicians. Genet Med. 2017;19(3):267-274. 2. Salmon K, Glass J, Genge A, et al. Amyotrophic lateral sclerosis (ALS) genetic testing: current landscape and potential needs. Presented at: American Academy of Neurology Virtual Annual Meeting; April 17-22, 2021. 3. Nguyen HP, Van Broeckhoven C, van der Zee J. ALS genes in the genomic era and their implications for FTD. Trends Genet. 2018;34(6):404-423. 4. Shepheard SR, Parker MD, Cooper-Knock J, et al; on behalf of Project MINE Consortium; Project MinE. Value of systematic genetic screening of patients with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2021;92(5):510-518.

References

1. Roggenbuck J, Quick A, Kolb SJ. Genetic testing and genetic counseling for amyotrophic lateral sclerosis: an update for clinicians. Genet Med. 2017;19(3):267-274. 2. Salmon K, Glass J, Genge A, et al. Amyotrophic lateral sclerosis (ALS) genetic testing: current landscape and potential needs. Presented at: American Academy of Neurology Virtual Annual Meeting; April 17-22, 2021. 3. Nguyen HP, Van Broeckhoven C, van der Zee J. ALS genes in the genomic era and their implications for FTD. Trends Genet. 2018;34(6):404-423. 4. Shepheard SR, Parker MD, Cooper-Knock J, et al; on behalf of Project MINE Consortium; Project MinE. Value of systematic genetic screening of patients with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2021;92(5):510-518.