Jennifer Roggenbuck, MS, LGC: Family members are hopefully educated about the ALS [amyotrophic lateral sclerosis] that’s in their family. When we see someone with ALS in the clinic, that patient is our patient. We’ve offered genetic testing, and we’ve given results to that patient. It’s up to the individual whether that information is shared with family members. Sometimes family members attend the appointments, and we have a chance to talk directly to them. Ultimately, it’s up to the family what information is shared and when and with whom, but any individual who has a relative diagnosed with a genetic form of ALS is a candidate for presymptomatic or predictive testing if they’re an adult. We don’t do this kind of testing on children in most cases, unless there are special circumstances—a teen, for example. It’s up to the family members if they want to come forward and seek genetic testing.

Family members tend to be quite different. In any given family, we see individuals who are seeking information and seeking that kind of testing; others decide against it. There’s no 1-size-fits-all approach when it comes to family members seeking genetic testing after a genetic diagnosis of an individual with ALS. We want those family members to be aware that that diagnosis has been made and that it’s possible to undergo testing themselves. We can facilitate this process by writing a letter that individuals with ALS can share with their family members, explaining what the genetic diagnosis is and what that means. This is likely to become more important in the future if we have approved therapies that can be given before the onset of symptoms. This isn’t something that we have now, but we hope that we’ll have some type of neuroprotective or preventive gene-targeted therapy in the future to offer healthy gene carriers before they have an onset of the disease.

The process for offering genetic testing to someone who has ALS with no family history entails explaining the basics of ALS genetics and that even in cases where there’s no family history, we sometimes find a genetic cause. Many individuals are surprised to hear that, so it’s important to convey the basics and then offer testing. In my practice, I offer comprehensive genetic testing in 1 step. That means we can do 1 genetic test and look for the known genetic causes for ALS all at once, whether an individual has a family history or not.

What’s different is the likelihood of finding a genetic cause. In someone doesn’t have a family history of ALS, the chance that we find a genetic cause is about 10%, whereas if someone has a family history of ALS, it’s a 50% to 60% chance. That part is different, but the testing process is the same whether someone has a family history of ALS or not. It’s always important to do that education and be sure that the individuals understand what the testing consists of, what the results might be like, and what the implications might be for themselves and their family members.

Laynie Dratch, ScM, CGC: Clinical practice for when and if genetic testing is offered varies greatly among different ALS clinics, in the United States and throughout the world. When would genetic testing be most valuable to include? It’s a little different from patient to patient because individuals might not be ready to approach genetic testing at the same time. There’s a lot to process cognitively and emotionally with a diagnosis of ALS. What’s critical is that it’s introduced as an option early on, that it’s offered early on, and that we let individuals decide for themselves when they’re ready. It’s most important that it’s on the table from the beginning of time when ALS is on the differential.

In some cases, it might be beneficial to offer genetic testing for genes related to ALS when individuals are still being worked up for ALS vs some other diseases. If you can get the genetic testing process started and get the result faster, it might lead to earlier ability to join a clinical trial or to initiate a therapy because genetic testing results are not immediate. They can take several weeks or months depending on what test is ordered and what lab the test is ordered from. The sooner that individuals start the genetic testing process, the sooner we can help figure out what some targeted therapies might be if a genetic cause is found. Right now, these are all targeted therapies that are research based. They’re not clinically proven or clinically approved. It should be offered early and discussed early, but some individuals may not be ready to pursue this right away. You shouldn’t have to wait to have a formal diagnosis of ALS to get this started. In our clinic, sometimes patients have 2 or 3 diseases they’re being worked up for. As long as there’s high enough concern that ALS could be a possibility, we’re comfortable proceeding with the genetic testing process so long as the family is OK with it.

It’s important to offer genetic testing to anybody with a diagnosis of ALS, regardless of whether they have a family history. A lot of factors go into knowing whether a family history of ALS or a related condition, like frontotemporal dementia, is present. Sometimes there might have been a family history of ALS, but the individuals who had symptoms never made it to the right diagnosis because it can be extremely challenging to get this diagnosis to rule out ALS. Or if there were other family members with ALS, the family might not have communicated this information to one another. Sometimes individuals will not have a family history of ALS even when they have a genetic form because other family members might have died young of other causes or might have had the genetic variant but never gone on to develop the disease. The individual in front of you with ALS might have a small family tree. For all of these reasons, a family history is a starting point to better understand the odds of a genetic cause, but the absence of a family history shouldn’t be an exclusion for the offer of genetic testing.

Although it’s much more common to find a genetic cause for ALS when there’s a known family history of another close relative with ALS or FTD [frontotemporal dementia], about 10% of individuals have no known family history of ALS but have an identifiable genetic cause for their disease. Because of this, regardless of family history, it’s important to offer genetic testing to anybody diagnosed with ALS. If a genetic cause for ALS is identified in a family, other family members who are asymptomatic might have the option to consider if they want to know their own genetic-risk status. This is a highly personal decision, learning if you’ve inherited the risk for ALS in the family. It’s a decision that should be made in the context of genetic counseling. It’s highly recommended that anybody who has a known genetic-risk factor in the family consider meeting with a genetic counselor if they have questions, even if they know they don’t want to pursue testing.

Before an individual who has risk based on family history pursues counseling or testing it’s important for them to think about the rules that protect them against privacy and discrimination issues and what those limitations are. In the United States, there’s a law called the Genetic Information Nondiscrimination Act, which has been in place since 2008. It says that, in most cases, your health insurance and your employer cannot ask for or use your genetic information against you in any way. There are exceptions if you work for the military, the federal government, or a small employer with fewer than 15 employees. If those 3 things don’t apply, then your health insurance and your employer can’t ask for or use your genetic information against you to fire you, fail to promote you, not hire you, or drop your coverage. We make our patients aware of this to point out the limitations in this law. Life insurance, long-term care insurance, and disability insurance don’t have these same protections. It’s important for individuals to think about what insurances they have in place and what they might want someday because once you have those policies set, they can’t be taken away.

Many individuals will think about what life, long-term-care, and disability insurances they have, and make sure they’re comfortable with them before they pursue genetic testing to learn their risk status. It’s possible that when individuals apply for those types of insurances, companies could request information about family history and genetic testing status, and then they could be denied coverage or charged a high premium. If an individual wants to think about genetic counseling with the option of testing, it can be done at any time once they’re aware of the result in the family. That can be an extremely challenging process, for the individual diagnosed or their care partner to have to share the genetic risk that’s been identified with those in the family. Often a genetic counselor can help with this process by providing things like family letters and copies of the test results. Sometimes family sessions might be available if the genetic counselor can help share information to many individuals in the family at the same time. That initial communication from the individual diagnosed or care partner to the family members who may be at risk, such as the children, siblings, or extended family, can be a very emotionally fraught process. It’s not something we tell individuals that they have to do the same day they learn of the genetic result. They can take time to process, but we encourage it to be done as soon as they’re comfortable because research shows that early and open communication is best in families with this. It reduces the odds of family members resenting them later on for having withheld this information.

We typically don’t recommend individuals think about predictive genetic testing—looking to see if they’re at risk based on family history—until they’re 18 years or older, because we really want it to be that individual’s own decision. Once they’re 18 or older and comfortable, they’re able to pursue the predictive counseling and testing if they want when there’s a known genetic cause of ALS in the family. If there isn’t a known genetic cause of ALS in the family, then predictive counseling and testing might be available. Counseling certainly is available. Testing might be available.

There are 2 situations when this happens. One situation is the individual with ALS in the family has high genetic testing but no cause has been found. In that situation, there isn’t appropriate testing we can offer that at-risk family member. In the situation where an individual has a family history of ALS but those relatives passed without having testing done, then that individual might consider testing broadly for the genes we know can cause ALS. It’s hard for us to interpret what a negative result would mean. It could mean there was a genetic cause of disease in the family, and this individual just didn’t inherit it—we looked in the right place, and they had a normal result. But it could also be the case that there was a genetic cause of disease in the family that’s a yet-to-be-discovered gene associated with ALS. When we tested the individual in front of us, we didn’t look in the right place; it’s a false negative. It can be challenging to navigate those conversations, but genetic counselors are trained to help individuals understand and be supported through this because it can be an emotional decision.

Transcript edited for clarity.