What is the difference between familial ALS and sporadic ALS?

ALS is considered to be ‘familial’ when at least two blood relatives have been affected with the disease. When there is no known history of ALS (or frontotemporal dementia) within a family, the ALS is considered to be ‘sporadic.’

Can the age of onset or progression of ALS be predicted with familial ALS?

Currently, we are not able to predict the age of onset of disease in people at risk for developing ALS. By contrast, in familial Alzheimer’s disease the age of onset of a parent is a reliable indicating of when disease is likely to develop in the next generation. Similarly, in Huntington’s disease, the size of the repeat expansion in the Huntingtin gene is a good predictor of when disease will develop. A major goal of our Pre-fALS study is to learn about factors that predict the age at which people are likely to develop ALS.

Will the results of genetic testing affect my ALS diagnosis/treatment?

Knowing the results of genetic testing does not affect your diagnosis of ALS. Currently, knowledge of the genetic cause of disease does not affect treatment either, but this is likely to change in the near future as clinical trials, which target the specific underlying genetic abnormality, are likely to begin within the next year or two.

How are ALS and Frontotemporal Dementia (FTD) related?

ALS and FTD were once thought to be entirely different diseases. We now recognize, however, that about a third of patients with ALS have some evidence of frontotemporal dysfunction and similarly that about a third of patients with FTD have some evidence of motor neuron pathology akin to that seen in ALS. Moreover, with advances in our genetic understanding of both ALS and FTD it has become clear that the same genetic abnormalities (e.g. the C9ORF72 repeat expansion) may cause ALS, FTD or a combination of the two. What causes some people to develop ALS, some to develop FTD and yet others to develop ALS-FTD is largely unknown, although progress is beginning to be made in identifying other genetic factors (e.g. TMEM106B) that may be protective against developing FTD.

What is familial ALS?

ALS that runs in the family is referred to as familial ALS (or “fALS” for short). If more than one member of your family has had ALS, then it is very likely that you belong to a fALS family. If only one person in your family has ever had ALS, then it is most likely that ALS does NOT run in your family.

What is genetic ALS and how is it different from familial ALS?

ALS is considered genetic when a mutation in a gene known to cause ALS is identified in someone who has ALS. Although it is at least theoretically possible than an environmental risk factor may cause ALS in multiple family members, no such environmental factors have been identified to date. As such, most forms of familial ALS are likely to be genetic. Importantly, however, a genetic cause of ALS is sometimes identified in people who do not have a family history of ALS.

How common is familial ALS?

Familial ALS is actually quite rare, with only about 10% of cases considered as familial.

I have a relative with ALS. How do I know whether our family has familial ALS?

ALS is not considered familial unless there are at least two people in the family who have ALS or have had ALS. These two people must also be blood relatives. On rare occasions, someone is diagnosed with ALS and although there is no history of other family members ever having had ALS, another family member is subsequently diagnosed with ALS, as well. Thus, it is possible that someone without a family history has familial ALS. This is unlikely and almost impossible to know until someone else in the family develops ALS.

What is a genetic mutation and how does it cause ALS?

A genetic mutation is a permanent change in the gene sequence of our DNA, or genetic code. This change may be due to a random even or some other mutagenic environmental factor. Our genes encode for proteins, which play a vital role in the various cellular functions of our bodies. When there is a change in the gene sequence that carries the blueprint for making a protein, that particular protein is altered too. It is the resulting disturbance in protein function that leads to disease, such as ALS.

How is familial ALS inherited?

Most of the genetic mutations implicated in causing ALS in the United States are inherited in a dominant fashion. This means that there is a 50% chance that a child will inherit the gene mutation from a parent. Importantly, the genetic cause of ALS in any particular family is always the same. That is to say, if the SOD1 gene is identified as the cause of ALS in one family member, then the SOD1 gene is also responsible for causing ALS in other family members. However, a small number of families have been identified with more than one gene mutation. It is important to note that the risk of inheriting the gene mutation is unique to each child, so the probability that any particular individual will inherit the gene is not influenced by whether or not a sibling inherited the gene mutation.

What are the known genetic mutations associated with familial ALS?

More than 30 different genes have been implicated in causing ALS. The most common include genetic mutations found in the C90RF72 and SOD1 genes. Other less-frequently occurring causes include genetic mutations in the FUS, VCP, and TARDBP (TDP-43) genes.

I am interested in genetic testing – Where do I start?

Before you decide to undergo genetic testing, you should speak with a genetic counselor. The genetic counselor will review your family history, explore the reasons you are considering testing and help you to understand the risks and benefits of genetic testing. The counselor will also discuss the potential results of genetic testing and the implications of both positive and negative results for you and for your children.

Once you have spoken with a counselor and decide that you would like to proceed with genetic testing, you will be asked to provide a DNA sample. DNA can be obtained from several sources although saliva and blood are the most common. Many laboratories prefer to do genetic testing on a blood sample. Depending on whether testing is done in a commercial (fee for service) laboratory or through a research study, it may take anywhere from 2-4 weeks to 2-3 months to obtain the results. Once the testing has been completed your genetic counselor will provide you with the results and review the implications of your specific result. You should also talk to your neurologist or other treating physician about the results of genetic testing and what they mean for you.

What is a Genetic Counselor?

Genetic counselors are health care professionals with specialized graduate training in the areas of medical genetics and counseling. Genetic counselors provide information and support to families who have members with birth defects or genetic disorders and to families who may be at risk for a variety of inherited conditions. To learn more about genetic counselors and the genetic counseling process click here.

How do I find a Genetic Counselor?

You can find a genetic counselor in your area by going to the National Society of Genetic Counselors website at www.nsgc.org and using the Find A Counselor function on the homepage.

Is it possible to get tested for familial ALS?

One can’t really get tested for familial ALS, but one can get tested for genetic ALS. Importantly, it is possible to test for some (but not all) of the genes that may cause familial ALS. However, having a genetic abnormality (typically called a gene mutation) in a gene known to cause an increased risk for developing ALS does not mean that you have ALS. If a person has a mutation in an ALS susceptibility gene that means there is a strong likelihood that they will develop ALS during their lifetime, however genetic test results cannot determine when or how symptoms of ALS will present.

How do I know if I should consider getting tested for a genetic abnormality that can cause ALS?

Genetic testing should only be considered in asymptomatic or healthy people if it has already been established that ALS runs in your family and a specific genetic abnormality (gene mutation) has been identified in a family member with ALS. Some reasons that unaffected people consider testing for genes known to cause ALS are:

  • To relieve the uncertainty surrounding the possibility of ALS risk and to be able to plan for the future.
  • Knowing if you have a gene mutation may influence your decision whether or not to have children.
    • If you do not have the gene mutation present in family members with ALS there is essentially no risk that you or your children could develop genetic ALS.
    • If you do have the gene mutation present in family members with ALS, there is about a 50% chance that you will pass the gene mutation onto a child.
    • There are reproductive options available for individuals who do not want to pass on the gene mutation associated with ALS risk to their children such as pre-implantation genetic diagnosis, using an egg or sperm donor and adoption.
  • To participate in research – Scientists are currently studying healthy relatives of people who have had ALS. This helps them learn more about the risk of developing familial ALS and whether it might be possible to prevent this disease in the future. If you’d like more information, please contact us at fals@med.miami.edu

Before deciding whether or not genetic testing for ALS risk is right for you, you should speak with a genetic counselor. See: How do I find a Genetic Counselor? and I am interested in Genetic Testing – Where do I start?

I have ALS - should I have genetic testing?

If you have ALS but you do not have a family history of ALS, there is no reason to undergo genetic testing at this time unless you are participating in a research program.

If you do have a family history of ALS, genetic testing may provide information about the gene responsible for your ALS and for the disease in your family. There are several reasons why you might consider having genetic testing. First, identifying a specific gene mutation associated with ALS risk may help to explain the reason for ALS in your family. If you know the gene and specific gene mutation that causes ALS in your family, healthy relatives will be able to decide if they would like to pursue genetic testing to learn more about their risk for developing ALS. Another reason to consider genetic testing is that you or family members might be eligible to participate in a clinical trial or other research program based on the results of genetic testing.

NOTE: We do not know all of the genes that can cause ALS. Thus, a negative genetic test results does not mean that you do not have genetic ALS.

If ALS is in our family, do I have familial ALS (fALS)?

It is important to draw a distinction between having ALS and being in a fALS family. You can be in a fALS family, but not have ALS yourself. You only have fALS if you come from a fALS family AND you have a diagnosis of ALS (i.e. have symptoms and signs of the disease and have been told by a neurologist or other specialist that you have ALS).

Do all family members with ALS have the same genetic abnormality?

Yes; all individuals within a family who have ALS will have the same genetic abnormality. For example, if you had a parent with ALS who was found to have a mutation in the SOD1 gene and you have now developed ALS, then it is assumed that you must carry the same SOD1 gene mutation. However, this should be confirmed by genetic testing. There are rare situations where mutations in more than one ALS susceptibility gene have been found in the same family. It is also very unlikely but possible that a person could be a member of a fALS family, not have the gene mutation in the family, but still develop sporadic ALS.

I tested positive for a known genetic mutation in an ALS susceptibility gene (SOD1, C9ORF72, FUS, VCP, etc…) - does that mean I have ALS?

No; testing positive for a known genetic mutation means that you have inherited an increased risk to develop symptoms of ALS during your lifetime, but it does not mean that you currently have ALS. Genetic test results cannot determine when or how symptoms of ALS will present. If you have symptoms that are of concern to you, you should seek advice from a neurologist.

I tested positive for a known genetic mutation of ALS. Will I develop ALS at the same time as my family member(s) did?

Not necessarily – while the average age to develop ALS may be the mid-forties to mid-fifties in fALS families, we see a wide range of variability in the age at which symptoms develop even among close relatives. Genetic testing can tell us that there is a significant risk for ALS to develop over the course of an individual’s lifetime, but cannot answer the question When?

If my genetic test results were negative does this mean that I don’t have genetic ALS?

No. Genetic testing does not tell you whether or not you have familial ALS. The testing tells you whether or not you have a mutation in one of the genes that may cause ALS. Even if you test negative for mutations in all of the genes that we know can cause ALS, you may still have genetic ALS. This is because not all of the genes that may cause genetic ALS have been identified.

What is the possibility of passing the genetic mutation to my children?

The chance of passing a genetic mutation in any of the known ALS susceptibility genes on to a child is 50%. All genes come as pairs and in most cases a single mutation in a pair of ALS susceptibility genes is enough to cause a significant risk to develop ALS. It is important to understand that each child has an independent chance of 50% to inherit the ALS gene mutation and 50% to inherit the normal copy of that gene. If a parent has 2 children, both children could inherit the mutation, both children could inherit the normal gene and 1 child could have the mutation and 1 child not have the mutation.

Who can I talk to about this?

If you have questions about genetic testing for ALS we encourage you to talk with a genetic counselor. You can find a genetic counselor in your area by going to the National Society of Genetic Counselors website at www.nsgc.org and using the Find A Counselor function on the homepage.

You can also contact our research staff at fals@med.miami.edu to learn more about the research opportunities, such as the Pre-fALS Study, for families with fALS.

What are the risks associated with undergoing a lumbar procedure?

The most common side effect of a lumbar puncture is a headache, also known as a “spinal headache.” Headaches most often occur in young women; however all age groups and genders could develop a headache. About 1 in 10 people will develop a spinal headache. This risk is further reduced through the use of a special “non-cutting” needle for the spinal tap, as well as drinking lots of fluids, specifically caffeinated beverages. On the rare occasion a spinal headache persists, your doctor may need to administer intravenous caffeine or perform a blood patch.

Are there research studies available for family members or relatives with familial ALS?

Yes. Scientists at the University of Miami are currently enrolling people for the Pre-symptomatic familial ALS (Pre-fALS) study. Relatives of family members who have had ALS and who may be at risk for carrying a faulty gene that causes ALS are eligible to participate in this study. The University of Miami pays for your annual visits to the University of Miami and for the genetic testing. We offer genetic testing and genetic counseling as part of the Pre-fALS study. You may choose to learn the results but you may also participate in this study without learning the results of genetic testing. If you would like to learn more information, please contact us at fals@med.miami.edu.

I don’t have ALS – are there any research opportunities available?

Yes. We are currently recruiting healthy individuals for our research studies and have several different opportunities available. To learn more, contact our research team at alsresearch@med.miami.edu.