Information On Genetic Testing

The decision to be tested is always yours. It is important to note that there are many variants in known ALS genes that don’t have sufficient research and information to fully understand their impact. Some physicians may hesitate to order genetic testing out of discomfort with not being able to provide comprehensive support to their patients trying to understand a complicated result. In Canada and the United States, an Ionis-sponsored genetic testing program is available through Prevention Genetics. Individuals may wish to bring this up with their clinician should they not already be aware. It is widely recommended that the panel testing is coupled with appropriate counselling.

Given that ALS-associated ALS-associated genetic variants have been identified in cases with no identifiable family history of ALS (seemingly “sporadic” cases), and that therapies targeting these variants are entering or underway in clinical trials, many experts are supportive of offering genetic testing to everyone with a diagnosis of ALS, when accompanied by appropriate genetic counselling. The availability of genetic counselling and testing varies between provinces. Genetic testing practices in ALS are rapidly evolving, but they are not enough to meet everyone’s needs.

Genetic testing in an individual at risk of developing a disease (with a known family history), but who is not currently exhibiting any symptoms, is called predictive testing.

As a consensus, predictive genetic testing for ALS is not recommended for children under 18 years old, because they cannot give their full consent. It is also extremely rare for ALS to develop in childhood, although variants in the FUS gene are known to have an earlier onset of disease and this may result in exceptions for predictive testing in childhood. Rarely, other variants also show early onset. Talking to a genetic counsellor about your family risk is encouraged.

• Reducing anxiety around the likelihood of developing ALS.
• Having time to accept and process the results regardless of whether they are positive or negative.
• Facilitating earlier diagnosis if symptoms manifest.
  • Earlier diagnosis of ALS can be significant in symptom management and eligibility for therapies and participation in clinical trials.
• Empowering individuals to advocate for themselves and the community.
• Finding a community, support, and services at an earlier stage.
• Opportunity to participate in research and future therapeutic trials.
  • Participating in research can be an empowering way to face ALS. There are observational studies for individuals with a known variant of ALS but not showing symptoms, and these are extremely important in understanding ALS progression.
  • Additionally, interventional research with potential therapeutics for pre-symptomatic individuals is emerging.
• Considering life decisions as well as understanding and mitigating potential risk factors.
  • This can be important as individuals consider career, health insurance, financial planning, and lifestyle choices.
• Considering the decision to have children and family planning.

• Learning about the results of genetic testing for ALS can be an incredibly challenging moment.
  • Some individuals might not be at the right time in their lives to face the results, especially if they don’t have access to counsellors or professional help.
• It can cause tension with other family members, who may not wish to know the test results.
• Genetic status may inadvertently reveal the status of another family member (e.g., if someone wants to get tested but their parent does not, twins, etc.).
• Individuals who have biological children might need to deal with feelings of anxiety related to ALS potentially being passed on.
• Potentially experiencing guilt about testing negative if other family members test positive.
• Positive results might mean having to rethink and change lifestyle, career, and insurance choices.

We encourage all families and individuals affected by a genetic form of ALS to stay on top of research breakthroughs and news relating to upcoming therapies in clinical trials as this is a rapidly advancing field.

For more information, you can refer to our fact sheet on genetic testing, which provides information on whether genetic testing is the right decision for you.

Sometimes, a genetic test result shows a change in the code (referred to as a variant) in a gene that we know is related to ALS, but the connection of that change to ALS is still unclear. This is called a variant of uncertain significance (VUS). For example, NEK1 is known as an ALS gene, but there are some changes in the NEK1 code that currently no one can reliably say causes or influences the development of the disease.

Sometimes the concern over how to explain a VUS to an individual, and the negative reaction and impact it can illicit, can be factors in a clinician’s hesitation to support genetic testing. This is also why pre- and post-test counselling is highly recommended. Often a VUS does not change clinical management, nor would predictive testing of family members be recommended. Sometimes there may be some follow up that the clinician can recommend trying to clarify the significance of the VUS, such as testing another family member with ALS (if applicable).

If someone has an identified VUS in a known ALS gene, it is important to note that the ALS research field has insufficient evidence to support it causing or increasing the risk of developing the disease. Research evidence is reviewed by top experts in the field on a regular basis. Research is also happening all the time to better understand ALS genetics and to inform the classification of genetic variants. A group of experts have even started a program where clinicians in the United States and Canada can get an assessment on any VUS identified in their patients.

There are resources that are frequently being updated with the latest evidence-based information on genetics, including when any VUS might have a status change to what is called a pathogenic or likely pathogenic variant, indicating that it is likely to cause or influence getting ALS.

Asking a physician, genetic counsellor, or research@als.ca for assistance is always recommended.

Some of these databases are on this page under additional resources.

Here is a geneticist describing VUS and how they are looked at by experts:

• If you have an ALS diagnosis or have been referred to a CALS clinic (the Canadian ALS Research Network) and would like to access testing, please refer to your neurologist or ALS clinic for more information as this varies by clinic and province. Most CALS clinics will offer genetic testing for individuals with a known family history. Given that variants in certain ALS genes have been seen in people without an identifiable family history, many clinics will test anyone with an ALS diagnosis for changes in genes that could provide them opportunities for treatment or participation in a clinical trial. If you don’t have a family history but are interested in genetic testing, please speak to your neurologist or ALS specialist for options.
  • You can refer your clinician to the Ionis-sponsored genetic testing program in case they are not aware of it.

• If you have a family history of ALS, and are experiencing symptoms that you are concerned may be related to ALS, ReferALS is a tool that can be provided to your doctor to help recognize early symptoms of ALS and encourage a referral to a neurologist or a specialized ALS Clinics if needed.

• Genetic testing in an individual at risk of developing a disease, but who is not currently exhibiting any symptoms, is called predictive testing and often requires extensive genetic counselling. Currently, only some ALS clinics offer predictive testing to at-risk, asymptomatic family members of someone who has/had ALS with a confirmed genetic variant.
• Please reach out to the ALS clinic who was responsible for providing care to your family member to discuss test options. You can also speak to your family physician about referrals to medical genetics and genetic counselling if you don’t have access to your family’s ALS clinic.
• In the absence of these options, ALS Canada may be able to facilitate through research@als.ca.

The vast majority (more than 75%) of ALS cases are not related to a known gene variant, meaning it is not passed on from parent to child. Therefore, if there is no known family history (i.e., multiple relatives carrying the genetic form of ALS) and it is an isolated case in the family, the likelihood of anyone else in the family getting ALS is similar to the general population. Some people may seek genetic testing for confirmation, but if you are not showing symptoms, access and appropriate counselling at present may be difficult without the confirmation of a family history.

ReferALS, which is a tool designed for community neurologists to recognize the symptoms of ALS, lists the common ALS symptoms and clinical features. You can read over the symptoms and save the tool. If you or other family members start showing symptoms described in the tool, you can show your family doctor to encourage an expedited referral to a neurologist or perhaps directly to a specialized ALS clinic.