Is Amyotrophic lateral sclerosis ALS hereditary?

Amyotrophic lateral sclerosis (ALS) is primarily classified as sporadic, meaning most cases occur in individuals with no family history; however, approximately 5% to 10% of cases are considered familial (hereditary). While genetic factors play a significant role in the development of familial Amyotrophic lateral sclerosis (ALS), the condition is typically multifactorial, involving a complex interplay between genetic predisposition and environmental triggers.

Is Amyotrophic lateral sclerosis (ALS) hereditary?

Most people diagnosed with Amyotrophic lateral sclerosis (ALS) have the sporadic form, which is not considered inherited. In contrast, familial Amyotrophic lateral sclerosis (ALS) follows an inheritance pattern, most commonly autosomal dominant, meaning a child of an affected parent has a 50% chance of inheriting the pathogenic variant. It is important to distinguish between "genetic" (caused by changes in DNA) and "hereditary" (passed from parent to child). While familial cases are hereditary, even sporadic cases may have an underlying genetic component that increases susceptibility.

What are the genetic patterns and risks involved?

The genetics of Amyotrophic lateral sclerosis (ALS) are heterogeneous, meaning many different genes can be involved. The most common genetic cause is a repeat expansion in the C9orf72 gene. Other frequently involved genes include SOD1, TARDBP, and FUS. While de novo (new, spontaneous) mutations do occur in some individuals, they are less common than inherited variants in familial cases. Because of the complexity of these mutations, risk assessment for family members is highly personalized and depends on the specific genetic variant identified in the affected individual.

When is genetic testing and counseling recommended?

Genetic testing for Amyotrophic lateral sclerosis (ALS) is generally recommended in the following scenarios:

• When there is a known family history of ALS or related conditions like frontotemporal dementia (FTD).


• For patients who wish to understand the etiology of their diagnosis to inform clinical trial eligibility.


• For asymptomatic relatives of an individual who has been found to carry a pathogenic mutation.


• For individuals seeking reproductive options, such as preimplantation genetic testing (PGT), to prevent transmission of a known mutation.

What is the role of genetic counseling?

Genetic counseling is a critical step for families affected by Amyotrophic lateral sclerosis (ALS). A counselor helps navigate the emotional and ethical implications of testing, interprets complex results, and discusses reproductive choices. For those planning pregnancies, counselors can explain the feasibility of prenatal diagnosis or PGT, which allows for the screening of embryos for specific mutations. With 333 people with Amyotrophic lateral sclerosis (ALS) currently sharing their experiences on DiseaseMaps.org, many in our community have found that speaking with a genetic counselor provides much-needed clarity during an overwhelming time.

Next steps

• Consult with a neurologist who specializes in neuromuscular disorders or a neurogeneticist to discuss the appropriateness of genetic testing.


• Seek a referral to a certified genetic counselor to review your family history and understand the implications of testing for you and your relatives.


• Connect with the DiseaseMaps.org community to learn from others navigating the diagnostic and genetic testing journey.


• Explore resources from organizations like the ALS Association or the Muscular Dystrophy Association for up-to-date clinical trial information.

Medical disclaimer: This information is for educational purposes only and does not constitute professional medical advice, diagnosis, or treatment; always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition.

References

• National Institutes of Health (NIH) Genetic and Rare Diseases Information Center (GARD): Amyotrophic Lateral Sclerosis.


• Orphanet: Amyotrophic lateral sclerosis.


• Online Mendelian Inheritance in Man (OMIM): Amyotrophic Lateral Sclerosis (ALS) entry #105400.


• The ALS Association: Genetics and ALS.