What is familial ALS?
ALS that runs in the family is known as “familial ALS” (or “fALS” for short). The type of ALS that doesn’t run in families is often called “sporadic ALS”. Familial ALS is very rare; only about 10% of all ALS cases are familial. A simple way to think about familial vs. sporadic ALS: 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.
I have a relative with ALS. How do I know whether our family has familial ALS?
This is a commonly asked question. The short answer is that ALS is not familial unless there are at least two people in the family who have ALS or have had ALS and these two people must be blood relatives. Very occasionally, 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.
If ALS is in our family, do I have 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).
How common is familial ALS?
Familial ALS is actually quite rare. Only about 1 in 10 people with ALS report having a family member who has also had ALS.
What is the cause of familial ALS?
Familial ALS is caused by a mutation. A mutation is a genetic change or abnormality in a particular gene. Sorting out which gene is to blame is complicated. Humans have about 50,000 genes, and in most people with familial ALS scientists have not yet identified which gene is responsible for causing ALS. What we do know is that in about 2 in 10 families with ALS, the disease is caused by a change in the superoxide dismutase, or SOD1, gene. Genetic changes in genes such as FUS and TDP-43 are the cause of ALS in an even smaller number of families with ALS, each accounting for approximately 1 in 20-25 families.
What are the differences between familial and sporadic ALS?
People with familial ALS look no different than people with sporadic ALS. In both the familial and sporadic disease, the symptoms are the same. These include increasing weakness, difficulty talking, swallowing and breathing as the disease progresses. The average age at which people develop symptoms of familial ALS is about 10 years younger than people with sporadic ALS, but there is tremendous variability in the age of onset. Some people with familial ALS may experience particularly rapid progression of disease due to specific genetic changes in the SOD1 gene.
Is it possible to get tested for familial ALS?
It is possible to test for some (but not all) of the genes that may cause familial ALS. However, having the genetic abnormality doesn’t mean that you have ALS. You might have the gene, but have not yet developed ALS. A diagnosis of ALS – either familial or sporadic – requires an examination and evaluation by a neurologist who is experienced in the field of ALS.
What are the genes that most commonly cause familial ALS?
Changes in the SOD1 gene are the most commonly identified cause of familial ALS. These account for about 2 in 10 patients with familial ALS. Other genes that may cause familial ALS include the FUS (fused in sarcoma) and the TDP-43 (tar-DNA binding protein-43) genes. Each of these genes accounts for 3-5% of patients with familial ALS. Mutations in a variety of other genes have been identified in very small numbers of people with familial ALS. These include genes such as FIG4, ANG, VAPB and senetaxin.
How is familial ALS inherited?
Most familial ALS, at least in the United States, is inherited in an “autosomal dominant” fashion. This means if one carries the gene, then there is a 50% chance of passing the gene onto one’s children. If you have a parent or sibling with ALS, there is a 50% chance that you also carry the genetic abnormality that can cause ALS. In Europe, and very rarely in the United States, familial ALS may be inherited in an “autosomal recessive” manner. This means there is a 25% (or 1 in 4) chance of passing the gene onto one’s children.
At what age does familial ALS begin?
The age of onset of familial ALS is variable, even within families. Although, on average, familial ALS begins about 10 years earlier than sporadic ALS, familial ALS may begin before the age of 20, after the age of 70, or anywhere in between. Often people with familial ALS may be fearful that they will develop the disease around the same age as their family member who had ALS. Currently, however, we don’t know very much about whether the age of onset of disease in a family member is of any value in predicting when someone else in the family will develop disease.
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 faulty SOD1 gene and you have now developed ALS, then of necessity, you must also have a copy of the faulty SOD1 gene.
Will knowing the results of genetic testing influence treatment for my ALS?
No; Riluzole (Rilutek) is a current treatment that is helpful in slowing the progression of ALS. Currently, there are several ongoing clinical trials for people with familial ALS, and in particular, only for people with ALS caused by a faulty SOD1 gene. If you’re interested in knowing whether or not you are eligible to participate in this kind of trial, there may be value in having genetic testing. If you would like to have genetic testing to find out if you are eligible to participate in a clinical trial, then please contact us (email@example.com) for more information.
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. 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. Currently, there is no ability to test for all genes that can cause ALS. Thus, a negative test does not mean that you do not have familial ALS.
There are several reasons why you might consider having genetic testing. First, if you know the gene that causes ALS in your family, healthy relatives may be able to undergo genetic testing to find out whether they are at risk for developing ALS. A second reason why you might consider genetic testing is that you or family members might be interested in participating in a clinical trial or other research program, for which only people whose genetic status is known, are eligible.
What types of procedures are involved in genetic testing?
Before you decide to undergo genetic testing, you should speak with a genetics counselor. The genetics counselor will help you to understand the risks and benefits of genetic testing and may also be able to help you explore the reasons why you have chosen to have testing. The counselor will discuss with you the potential results of genetic testing and the implications of both positive and negative results for you and for your children. Once you’ve spoken with a counselor and have made a definite decision to have testing, then you will need to provide a DNA sample. DNA can be obtained from several sources including saliva and blood, although scientists often prefer to collect blood. Once scientists receive your blood or saliva sample, they extract the DNA and perform the genetic testing. Depending on which scientist or laboratory is doing the genetic testing, it may take anywhere from 2-4 weeks to 2-3 months to obtain the results. Once the testing has been completed you should again talk with a genetics counselor who will provide you with the results and also talk to you about the implications of the specific result that you have received. You should also be able to talk to your neurologist or other treating physician about the results of genetic testing and what they mean for you.
If I’ve tested negative, does this mean that I don’t have familial ALS?
No. Genetic testing does not tell you whether or not you have familial ALS. The testing tells you whether or not you have one of the known faulty genes that may cause ALS. Even if you test negative for faulty copies of all the genes that we know can cause ALS, you may still have familial ALS. This is because not all of the faulty genes that may cause familial ALS have been identified.
I am concerned that I may be at risk for familial ALS – should I have genetic testing?
Genetic testing should only be considered if it has already been established that ALS runs in your family and a faulty gene has been identified in a family member with ALS. If ALS does run in your family (and you know which gene is responsible), but you don’t yet have symptoms, there are several reasons why you might consider genetic testing. The first is that knowing if you have a copy of the faulty gene may influence your decision whether to have children. If you don’t carry the faulty gene, there is no risk that your children could develop familial ALS. If you do have the faulty gene, there is usually about a 50% chance that you will pass the gene onto a child. The other reason to consider genetic testing (even if you don’t have ALS) is that 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 firstname.lastname@example.org.
Which clinical trials are particularly relevant to patients with familial ALS?
There are currently two trials open only to people with familial ALS that is caused by a faulty copy of the SOD1 gene. These include:
- A phase II/III trial of Arimoclomol that is being conducted by scientists at University of Miami, FL.
- A phase I trial of pyrimethamine that is being conducted by scientists at Weil Cornell Medical College, NY.
If you would like more information about any of these trials, please contact us at email@example.com.
Are there studies available for family members of relatives with familial ALS?
Yes. Scientists at the University of Miami are currently enrolling people for the Pre-familial (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 firstname.lastname@example.org.