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Is ALS Hereditary?

Amyotrophic lateral sclerosis (ALS) is a condition that has undefined causes and a very unpredictable nature. While the majority of ALS cases are sporadic, meaning that they have no defined origin, certain cases seem to have a hereditary component. 

Familial ALS: A Clear Genetic Link

About 5-10% of ALS cases are familial. One copy of the mutated gene, inherited from one parent, is needed to develop the condition since familial ALS is inherited in an autosomal dominant form. Every pregnancy carries a 50% chance of passing the mutated gene from the affected parent to the kid. The mutated gene does not ensure the development of ALS symptoms, however, it does increase the likelihood of once developing them.

Major Genetic Contributors to ALS

A number of genes have been connected to familial ALS, however, they affect the condition differently.  

  • C9orf72: The expansion of a hexanucleotide repeat in this gene is seen in many cases of familial ALS. It is the most often linked gene to frontotemporal dementia and familial ALS.
  • SOD1: Up to 20% of instances of familial ALS are caused by mutations in SOD1, the first gene connected to the disease.
  • TARDBP and FUS: Mutations in these genes are less common, but they have been linked to familial ALS.
Each of these genes plays a role in neural health and function, and their mutations lead to the characteristic motor neuron degeneration seen in ALS.

The Complexity of Heredity and ALS

The existence of these genetic mutations raises critical questions about the nature of ALS heredity:

  • Variable Penetrance: Not everyone who is born with a gene mutation linked to ALS will experience the illness. It also means the involvement of extra factors, such as environmental influences or additional genetic modifiers.
  • Anticipation: An occurrence known as anticipation occurs when some families with hereditary ALS suffer from an earlier development of symptoms in generations to come. This has been observed especially in families where the mutation C9orf72 is present.
  • De Novo Mutations: In certain cases, a familial form of ALS shows without a previous family history. De novo mutations can happen spontaneously in the early stages of embryogenesis.

Genetic Counseling in ALS

Genetic counseling is an essential part of the process for families affected by ALS, given the serious consequences of genetic testing. It may help individuals understand the nature of the illness and the risks associated with inheritance.

Research into these hereditary links may eventually lead to improvements in ALS by helping us predict, prevent, and treat this disease.

Credits:
Amyotrophic lateral sclerosis
FYI: Familial Amyotrophic Lateral Sclerosis (FALS) and Genetic Testing
FAMILIAL ALS: RESOURCE BOOKLET

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