New guidelines: All ALS patients should be offered genetic testing

The guidelines include 35 recommendations supported by clinical evidence

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

Share this article:

Share article via email
This is an illustration of a DNA strand.

Every person with amyotrophic lateral sclerosis (ALS) should be offered genetic testing to check for the most common ALS-causing mutations, according to a new set of expert guidelines.

“These evidence-based, consensus guidelines will support all stakeholders in the ALS community in navigating benefits and challenges of genetic testing,” Stephen Kolb, MD, PhD, a professor at The Ohio State University and co-author of the guidelines, said in a press release.

The study, “Evidence-based consensus guidelines for ALS genetic testing and counseling,” was published in the Annals of Clinical and Translational Neurology. The work was funded by the ALS Association.

Recommended Reading
An illustration shows neurons protected by a myelin sheath.

NEK1 gene mutations found to drive ALS in new study

The causes of ALS remain incompletely understood, but in recent decades it has been shown that genetic mutations are responsible for at least some cases of the disease. Genetic ALS is more common in people with familial ALS who have a family history of the disease, but they are found in about 10% of people with sporadic ALS who don’t have a family history.

“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,” Kolb said.

“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,” added Jennifer Roggenbuck, a genetic counselor at Ohio State and co-author of the guidelines.

In order to help advance ALS genetic testing, the scientists conducted a review of the available scientific literature, combined with expert opinion, to formulate new guidelines on genetic testing for people with ALS.

“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,” Roggenbuck said.

Looking for mutations in the most common ALS-linked genes

The guidelines, a set of 35 recommendations supported by clinical evidence, state that every person with ALS should be offered genetic testing to look for mutations in the most common ALS-linked genes, including at least C9ORF7SOD1, FUS, and TARDBP.

The guidelines provide some specific guidance about the best types of laboratory procedures to detect mutations in these genes. They note that, as research continues to identify new ALS-linked genes, other genes strongly linked to ALS also should be included in genetic testing.

“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.

The guidelines also note that, as new therapies become available to treat specific genetic forms of ALS, all patients should be offered genetic testing for the relevant gene(s). For instance, the therapy Qalsody (tofersen) was recently authorized in the U.S. to treat ALS associated with mutations in the SOD1 gene.

Include genetic counseling with genetic testing

The guidelines stress that, in addition to offering genetic testing, it’s crucial for patients to also receive genetic counseling — consultation with a genetic counselor or another specialist that can help patients to understand the ramifications of genetic testing results.

Genetic counseling should be done both before genetic testing (so that patients can understand the possible outcomes of the testing) and also after the testing to discuss the results. In addition to discussing the implications for the individual being tested, it also is important for counselors to clearly discuss the potential implications for the person’s family members, the guidelines note.

A key part of these discussions, according to the guidelines, is ensuring that patients are aware of the limitations of genetic testing.

For example, because only a few ALS-causing mutations are known, most people with ALS probably won’t have any notable results — and even if genetic testing is negative for known mutations, that doesn’t rule out the possibility that other not-yet-known mutations may be present. And even when a mutation is identified, this doesn’t always provide actionable information about the disease’s prognosis or treatment options.

“These evidence-based, consensus guidelines for ALS genetic testing, counseling and methodologies are meant to establish a standard of care in clinical practice for individuals with ALS,” the scientists wrote.

Genetic test for ALS guidelines should be up-to-date

The researchers emphasized that these guidelines will need to be periodically updated as more is learned about the genetic underpinnings of ALS.

“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,” Roggenbuck said.