Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the brain and spinal cord. These neurons control voluntary muscles, and their degeneration leads to muscle weakness, atrophy, and the eventual loss of the ability to move, speak, eat, and breathe. The question of whether ALS can be passed down from a grandparent to a grandchild is complex, touching upon the genetic basis of the disease. While most cases are not hereditary, genetic transmission across generations exists, primarily within a specific, less common form of the condition.
Differentiating Sporadic and Familial ALS
ALS cases are categorized into two main groups based on family history. The most common form is Sporadic ALS (SALS), accounting for approximately 90–95% of all diagnoses. SALS has no apparent family history, and its cause is largely unknown, though environmental and genetic factors are thought to play a role.
Familial ALS (FALS) is the less frequent form, making up about 5–10% of cases. FALS is defined by having two or more family members diagnosed with the disease, suggesting an inherited genetic cause. The risk of transmission from a grandparent is tied almost exclusively to this familial category, as SALS does not follow a pattern of inheritance.
FALS often presents at a slightly earlier age than SALS, though the clinical symptoms and disease progression are essentially the same. Some cases initially classified as SALS may actually have a genetic component that was not obvious due to incomplete family history. This suggests the line between the two forms can sometimes be blurred, particularly as genetic testing becomes more common.
Understanding Genetic Inheritance and Penetrance
When ALS is familial, it is typically passed down through Autosomal Dominant inheritance. This means a person only needs to inherit one copy of the altered gene from one parent to potentially develop the condition. A parent carrying the genetic change has a 50% chance of passing that mutation on to each child.
Dozens of different genes have been associated with FALS, with the C9orf72 and SOD1 genes being the most common contributors. Mutations in the C9orf72 gene, for instance, account for a large percentage of familial cases and are also linked to frontotemporal dementia (FTD). This inheritance pattern explains how a grandchild could potentially inherit the risk, as the mutation can be passed from the grandparent, through the parent, to the child.
The concept allowing a grandparent to pass the disease-linked gene to a grandchild, even if the parent did not develop ALS, is called incomplete or reduced penetrance. Penetrance is the likelihood that someone carrying a specific gene mutation will develop the disease in their lifetime. Incomplete penetrance means that having the gene mutation does not guarantee the disease will manifest.
For FALS, penetrance is variable, meaning some individuals who inherit the altered gene may never show symptoms. This variable expression can make it appear as though the disease has “skipped” a generation, when the intervening parent carried the gene mutation silently. Penetrance often increases with age, but the maximum penetrance for some common ALS genes, like C9orf72, is estimated to be around 33% at the population level.
Practical Steps for Risk Assessment
For individuals concerned about a grandparent’s ALS diagnosis, the first practical step is to document a detailed family medical history. This involves confirming if the grandparent’s case was definitively FALS, which means determining if other family members across multiple generations were also affected by ALS or FTD. A genetic counselor will construct a pedigree, or family tree, that may go back to great-grandparents to assess the risk.
Genetic counseling is recommended for anyone interested in understanding their potential hereditary risk. A genetic counselor is trained to interpret complex family history, explain the nuances of inheritance patterns and penetrance, and provide a personalized risk assessment. They help individuals weigh the emotional, social, and medical implications of genetic testing.
If the family history strongly suggests FALS, genetic testing can be considered to look for known ALS-linked mutations like those in C9orf72 or SOD1. This is a personal decision that requires careful discussion with a counselor. A positive result for an asymptomatic person provides information about risk but cannot predict the exact age of onset or disease progression. Genetic testing is often offered to all persons with ALS, and the results can inform relatives about their risk and potential eligibility for gene-targeted therapies or clinical trials.