Navigating Genetic Testing in ALS

Understanding Options, Benefits, and Cost

Rich Dineen, MS, CGC, Certified Genetic Counselor, Section of Neuromuscular Disease, Rush University Medical Center

Many individuals and families have questions regarding genetic testing options for ALS, especially now that there is a treatment option for ALS caused by a gene known as SOD1.  There is also the hope for additional treatment options for other genetic forms of ALS in the future.  As genetic testing for ALS has evolved significantly in the past few years, I will attempt to review some of the reasons to consider testing and review some of the associated costs. 

Current guidelines suggest that genetic testing be offered to all individuals who receive a diagnosis of ALS.  It is important to remember that genetic testing is not being offered to confirm the diagnosis of ALS but is being offered to determine if the cause of ALS may be determined.  Approximately 10% of those who are diagnosed with ALS will have a genetic cause identified.  Those with a prior family history of ALS (familial ALS) have the highest chance of receiving positive genetic test results.  However, those with no prior family history (sporadic ALS) may also have positive results although the chances are much lower. 

The primary reason genetic testing is offered to all individuals is to determine if that person may qualify for one of the approved treatments for genetically caused ALS, such as QALSODY (tofersen).  Those with positive genetic results may also qualify for existing or upcoming clinical trials related to a specific genetic form of ALS.  In these instances, the results of genetic testing could change the medical management for that person. 

Another common reason people diagnosed with ALS request genetic testing is to better determine the risk to their children or other family members.  Generally, the risk to first degree relatives for those with no family history of ALS is approximately 2-3%.  On the other hand, those who are identified as having a genetic form of ALS may have a risk as high as 50% for other family members to inherit the same genetic form of the condition. 

In the past, technical issues made genetic testing more complicated.  For example, the most common gene associated with genetic ALS, C9orf72, requires specialized genetic testing and is tested differently than most genes.   Because of those differences, fewer laboratories performed testing of this gene. Today, testing of the C9orf72 gene can be performed alongside testing of other genes known to cause ALS. 

Many genes have now been identified as causes of ALS.  Genetic testing techniques allow for testing a group of genes simultaneously.  Several laboratories now perform genetic testing by analyzing a little over 30 genes related to ALS.   While most people anticipate clear results from genetic testing, it is also important to mention that genetic testing can at times identify uncertain results.  In many instances, these uncertain results can be resolved through additional research. 

Costs associated with genetic testing prevented many from pursuing this option in the past.  The cost of genetic testing has decreased significantly in the past few years.  Additionally, there are currently two sponsored genetic testing programs that allow for no cost genetic testing.  Sponsored genetic testing programs are supported by pharmaceutical companies, which have contracted with known genetic testing laboratories ensuring the testing is of high quality.   However, in a sponsored genetic testing program the sponsor would have access to the individual’s genetic information (although this information would not be connected to identifying information).  If someone is not comfortable with a sponsored genetic testing program, testing could be performed through use of insurance or several laboratories have cash options for testing, some for as low as $250. 

While not every individual who undergoes genetic testing will consult a genetic counselor, there are situations where such a meeting can be beneficial.   Some individuals, especially those with family history of ALS or a related condition as indicated by a family member’s positive test results, may be interested in presymptomatic testing.   A genetic counselor can help them understand the limitations of positive test results, which cannot predict the age of onset or the types of initial symptoms the person may experience.   The impact of positive genetic testing results on family planning, including family planning options, could be discussed.  Finally, information on how genetic testing results might affect employment and different types of insurances (health, life, disability) would be reviewed.     

If genetic testing has not been offered to you in the past, you can discuss this option with your treating neurologist.  Furthermore,  several ALS clinics employ genetic counselor as part of their team and who can discuss these options in more detail.  Recent changes in genetic testing have removed many barriers, hopefully making it more accessible to everyone.