About genetic amyotrophic lateral sclerosis (ALS)

The progressive loss of motor neurons in the brain and spinal cord is characteristic of ALS.1 It is a complex disease, which is likely underpinned by different pathogenic mechanisms including multiple genetic factors.2

Historically, ALS has been divided into two categories -
familial ALS (fALS) and sporadic ALS (sALS).

Recently it has been found that not only patients living with familial ALS (fALS) may have a genetic component to their disease. A genetic component may be found in both familial and sporadic ALS. Scientific discoveries have identified more than 25 ALS-associated genes—which can be found in both fALS and sALS cases—that may play a role in disease pathology.2

Sporadic ALS

The majority of ALS patients are classified as sporadic ALS (sALS), however, many of these patients may be unaware of a family history of the disease.1 Currently, sALS is 90% of the total ALS population and of these approximately 10% have a known genetic component.3-6

Familial ALS

Familial ALS (fALS) is defined by a known family history, where more than one relation has a confirmed diagnosis of ALS.1 Currently, fALS is estimated at 5% to 10% of the total ALS population2—of these, approximately 70% have a known genetic component.7

Genetic ALS

Even seemingly sporadic ALS could have a genetic component. Research has shown that almost 10% of sALS may have a genetic link. Learn more about the latest in genetic mutations associated with ALS.3-6


On the multi-step theory

Prof. Vucic—Professor of Medicine at the University of Sydney’s Westmead Clinical School—posits that ALS is a complex, multi-step process in which genetic mutations play an important—even foundational—role, but in which several other factors are at play.8

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Cortical hyperexcitability

Prof. Kiernan—Bushell Chair of Neurology at the University of Sydney—and his colleagues have investigated the connections between cortical hyperexcitability and genetic ALS mutations, and how those connections might affect disease onset.

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References: 1. Brown RH, Al-Chalabi A. Amyotrophic Lateral Sclerosis. NEJM. 2017; 377: 162-72. 2. Nguyen HP, Van Broeckhoven C, van der Zee J. ALS Genes in the Genomic Era and their Implications for FTD. Trends Genet. 2018;34(6):404-423. 3. Zarei S, Carr K, Reiley L, et al. A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int. 2015;6:171. 4. Byrne S, Walsh C, Lynch C, et al. Rate of familial amyotrophic lateral sclerosis: a systemic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2011;82:623-627. 5. Volk E, Weishaupt JH, Andersen PM, et al. Current knowledge, and recent insights into the genetic basis of amyotrophic lateral sclerosis. Medgen. 2018;30:252-258. 6. Arthur KC, Calvo A, Price TR, et al. Projected increase in amyotrophic lateral sclerosis from 2015 to 2040. Nat Commun. 2016;7:12408. 7. Renton AE, Chiò A, Traynor BJ. State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci. 2014;17(1):17-23. 8. Chiò A, Mazzini L, D’Alfonso S, et al. The multistep hypothesis of ALS revisited: the role of genetic mutations. Neurology. 2018;91(7):e635-e642. doi:10.1212/WNL.0000000000005996. 

References

1. Brown RH, Al-Chalabi A. Amyotrophic Lateral Sclerosis. NEJM. 2017; 377: 162-72. 2. Nguyen HP, Van Broeckhoven C, van der Zee J. ALS Genes in the Genomic Era and their Implications for FTD. Trends Genet. 2018;34(6):404-423. 3. Zarei S, Carr K, Reiley L, et al. A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int. 2015;6:171. 4. Byrne S, Walsh C, Lynch C, et al. Rate of familial amyotrophic lateral sclerosis: a systemic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2011;82:623-627. 5. Volk E, Weishaupt JH, Andersen PM, et al. Current knowledge, and recent insights into the genetic basis of amyotrophic lateral sclerosis. Medgen. 2018;30:252-258. 6. Arthur KC, Calvo A, Price TR, et al. Projected increase in amyotrophic lateral sclerosis from 2015 to 2040. Nat Commun. 2016;7:12408. 7. Renton AE, Chiò A, Traynor BJ. State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci. 2014;17(1):17-23. 8. Chiò A, Mazzini L, D’Alfonso S, et al. The multistep hypothesis of ALS revisited: the role of genetic mutations. Neurology. 2018;91(7):e635-e642. doi:10.1212/WNL.0000000000005996.