Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects motor neurons, the nerve cells responsible for controlling movement.
In about 10% of cases, ALS is familial, meaning the disease does or did affect more than one person in the same family. Most patients, in contrast, have no such family history of the disease, and are considered as having sporadic ALS. The symptoms of both forms are similar, which can make it difficult to distinguish between the two.
Of note, people with familial ALS tend to develop symptoms earlier in life than those with sporadic ALS.
Genetics of familial ALS
With familial ALS, certain genetic mutations can predispose an individual to develop the disorder, and these disease-driving mutations may be passed from parents to their children.
The most common ALS-associated genetic mutations occur in the C9orf72, SOD1, TARDBP, and FUS genes. However, as new disease-causing mutations are continually being discovered, only about two-thirds of familial ALS patients know exactly their disease-driving mutation.
How ALS is inherited depends on the specific mutation. Most mutations are inherited in an autosomal dominant pattern, meaning one copy of the mutated gene is sufficient to drive ALS. Since most people have two copies of each gene (one from each biological parent), a person with this type of familial ALS would have a 50% chance of passing the mutated gene to their children.
Notably, genetics alone are not sufficient to cause ALS. It is possible that someone with a genetic disposition will never experience disease symptoms in their lifetime; ALS depends on a host of factors that impact its development, and many are not well-understood.
Genetic testing, done via a blood or saliva sample, may be used to identify mutations associated with familial ALS. This form of testing can be recommended if more than one person in a patient’s family has ALS or a related condition called frontotemporal dementia. If a disease-associated mutation is identified, biological family members without any symptoms may also be tested to determine if they inherited the genetic mutation. This is called predictive testing.
Currently, no gene-specific treatment options are available for ALS patients, but knowing the disease-causing mutation may make a patient eligible for certain clinical trials, including those of investigative treatments.
The decision to undergo genetic testing is always a personal choice; genetic counseling may be useful in deciding whether or not to be tested.
Last updated: Nov. 2, 2021
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