Learn More: Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s Disease, is a late-onset and rapidly-progressing neurodegenerative disease.¹ Most cases of ALS appear in individuals with no family history of ALS, referred to as sporadic. The mean age of onset of sporadic ALS is 56 years of age. This differs from the familial, or inherited, form of ALS, where the mean age of onset is 46 years of age.

Genetics and ALS Disease

Inherited forms of ALS represent 5-10% of all ALS cases. To date, more than a dozen causative genes have been identified in hereditary ALS and more than 30 others have been identified as potentially causative or disease-modifying.^{2, 3}

Reasons for Genetic Testing

Multiple hereditary disorders may present similarly to ALS. These include, but are not limited to, spinal and bulbar muscular atrophy, spinal muscular atrophy, distal hereditary motor neuronopathies, primary lateral sclerosis, hereditary spastic paraplegia, hexosaminadase A deficiency, adult polyglucosan body disease, and more.

Confirmation of a clinical diagnosis through genetic testing can direct medical management, help predict progression of the disease, and provide essential information related to risk for relatives. In particular, testing is recommended for:

• Individuals with a family history of ALS and presentation of the most common clinical symptoms
• Individuals without a positive family history, but who have experienced the most common clinical symptoms
• Carrier testing may be possible in individuals with a family history, but it is more informative when a genetic cause has been identified in an affected relative. Predictive testing should be undertaken after appropriate genetic counselling

 LifeLabs Genetics offers the following Next-Generation Sequencing panels (Sequencing, Copy Number Variant analyses, and Repeat Expansion analyses)

• Amyotrophic Lateral Sclerosis (ALS) Panel: ALS2, ANG, CHCHD10, CHMP2B, DCTN1, ERBB4, FIG4, FUS, HNRNPA1, MATR3, NEFH, OPTN, PFN1, PRPH, SETX, SIGMAR1, SOD1, SPG11, SQSTM1, TARDBP, TBK1, TUBA4A, UBQLN2, VAPB, VCP

*Includes repeat expansion analysis of ATXN2 and C9orf72

 References

1. Kinsley L, Siddique T. Amyotrophic Lateral Sclerosis Overview. GeneReviews®. Adam MP, Ardinger HH, Pagon RA, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2018. Last update 2015.
2. Al-Chalabi et al. Gene discovery in amyotrophic lateral sclerosis: implications for clinical management. Nat Rev Neurol. 2017 Feb;13(2):96-104.
3. Hong-Fu Li et al. Genotype-phenotype correlations of amyotrophic lateral sclerosis. Transl Neurodegener. 2016; 5: 3.