Where no family history of the disease is present – i.e., in around 95% of cases – there is no known cause for ALS. Potential causes for which there is inconclusive evidence includes head trauma, military service, and participation in contact sports. Many other potential causes, including chemical exposure, electromagnetic field exposure, occupation, physical trauma, and electric shock, have been investigated but without consistent findings.
There is a known hereditary factor in familial ALS (FALS), where the condition is known to run in families. Recently, a genetic abnormality known as a hexanucleotide repeat was found in a region called C9ORF72, which is associated with ALS combined with frontotemporal dementia ALS-FTD, and accounts for some 6% of cases of ALS among white Europeans. The high degree of mutations found in patients that appeared to have "sporadic" disease, i.e. without a family history, suggests that genetics may play a more significant role than previously thought and that environmental exposures may be less relevant.
A defect on chromosome 21 (coding for superoxide dismutase) is associated with approximately 20% of familial cases of ALS, or about 2% of ALS cases overall. This mutation is believed to be autosomal dominant, and has over a hundred different forms of mutation. The most common ALS-causing SOD1 mutation in North American patients is A4V, characterized by an exceptionally rapid progression from onset to death. The most common mutation found in Scandinavian countries, D90A, is more slowly progressive than typical ALS and patients with this form of the disease survive for an average of 11 years.
Mutations in several genes have also been linked to various types of ALS, and the currently identified associations are shown in the table below.
|ALS14||613954||VCP||9p13.3||Very rare, described only in one family|
|ALS15||300857||UBQLN2||Xp11.23–p11.1||Described in one family|
|ALS16||614373||SIGMAR1||9p13.3||Juvenile onset, very rare, described only in one family|
|ALS17||614696||CHMP2B||3p11||Very rare, reported only in a handful of patients|
|ALS18||614808||PFN1||17p13.3||Very rare, described only in a handful of Chinese families|
Read more about this topic: Amyotrophic Lateral Sclerosis