Neurology / genetic disease · BEGINNER LESSON

Familial ALS

Familial ALS is amyotrophic lateral sclerosis that occurs in a family pattern, usually because inherited genetic variants are present in one or more relatives. It is a subset of ALS, which means it shares the same nerve-cell disease but has a clearer inherited background than sporadic ALS.

AI-assisted lesson · Public sources · Updated 2026-10-11

What familial ALS is

Familial ALS is a family-pattern form of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease that affects motor neurons, the nerve cells that control movement. In published sources, about 5–15% of ALS cases are familial, and many—but not all—have an identifiable inherited genetic cause. Common genes named in these reports include C9orf72, SOD1, TARDBP, and FUS. [ALS means amyotrophic lateral sclerosis; genetic means related to DNA variants passed through families.] [0,1,2]

[1] The differences in sex ratio between sporadic and familial ... [2] pmc.ncbi.nlm.nih.gov › articles › PMC12941290Amyotrophic Lateral Sclerosis (ALS) Genetics and Microbiota ... [3] Update and recommendations on genetic testing for amyotrophic lateral sclerosis in clinical practice: a Brazilian expert view

How it is identified

Familial ALS is usually recognized by family history, sometimes together with genetic testing. Different studies and clinics use different definitions: some count one affected close relative, while others require multiple affected relatives or a known disease-causing variant. One published approach classifies cases as definite, probable, or possible familial ALS depending on relatives with ALS and whether a monogenic [single-gene] basis is found. [1,2]

[2] pmc.ncbi.nlm.nih.gov › articles › PMC12941290Amyotrophic Lateral Sclerosis (ALS) Genetics and Microbiota ... [3] Update and recommendations on genetic testing for amyotrophic lateral sclerosis in clinical practice: a Brazilian expert view

What causes it

The sources describe familial ALS as often caused by inherited mutations, but not always by a single gene change. C9orf72 repeat expansion is highlighted as the most common genetic cause in many populations, while SOD1, TARDBP, and FUS are also important. Other genes and genetic risk factors can contribute, and the exact biology is complex rather than one simple pathway. [2,1]

How it differs from sporadic ALS

Sporadic ALS means ALS with no clear family pattern. The sources note that most ALS cases are sporadic, and that the boundary between sporadic and familial can be blurred because family history may be incomplete, definitions differ, and some affected families have no single mutation identified. [0,1,2]

Limitations and uncertainty

The main limitation in studying familial ALS is inconsistent definition across studies and clinics. Some papers classify by relatives, others by genetic findings or medical records, so results are not perfectly comparable. A standard clinical definition is still lacking, even though consistent definitions would improve research and counseling. [0,2]

[1] The differences in sex ratio between sporadic and familial ... [3] Update and recommendations on genetic testing for amyotrophic lateral sclerosis in clinical practice: a Brazilian expert view

SEE THE IDEA

Familial ALS: from family pattern to diagnosis

01Family history

More than one affected relative can suggest familial ALS.

02Genetic testing

Tests look for variants in genes such as C9orf72, SOD1, TARDBP, and FUS.

03Clinical ALS diagnosis

Doctors still diagnose ALS mainly by symptoms and signs of motor neuron disease.

04Classification limits

Different study definitions can place the same family in different categories.

Family history and genetic testing help identify familial ALS, but clinical diagnosis and study classification can still vary.

Familial ALS is identified by a mix of family pattern, genetic findings, and clinical evaluation, with no single universal research definition.

TRY IT YOURSELF

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0 of 3 questions answered

01 A patient has ALS and two close relatives with ALS. Which classification best fits the descriptions in the sources?

02 Which gene is repeatedly named as one of the major genetic causes of familial ALS?

03 A study counts familial ALS only when there is one affected first-degree relative, while another study requires a known pathogenic variant. What problem does this create?

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Sources and further reading

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