How does having a parent with sporadic ALS affect a persons risk for ALS? Are people with a close relative with sporadic ALS at a higher risk for ALS than those without a family history of it?
The estimated general population risk for ALS
is a small fraction of one
percent. Less than 3 people in 100,000 are diagnosed with ALS each
year in the United States. Studies suggest that people with a closely related relative (e.g., parent or sibling) have a small, but definite increased risk for ALS. Siblings are estimated to have a 0.5% risk, while offspring a 1% risk.
Last updated: 8/5/2015
Have there been cases where a person with sporadic ALS has become the
first family member with familial ALS with autosomal dominant inheritance?
Yes. Studies have found "de novo" autosomal dominantgenemutations in
people with ALS. A de novo gene mutation is a mutation that occurs
for the first time in a family as a result of a spontaneous gene change in the egg or sperm or in a fertilized egg soon after
These research findings, and rare case reports, support that this is
possible. It is common for these mutations to be very unique to a family, and so
very little is often known about the specific mutation. Factors such as "reduced penetrance" have also been reported in these cases, making it very difficult to predict if a person will develop ALS. Reduced penetrance means that a person with the ALS-associated gene mutation may never develop ALS.
Studies are underway to improve our understanding of how genetics plays a
role in both sporadic and familial cases of ALS. Hopefully this knowledge will give
families more definitive answers about recurrence risks.
Mandich P et al.,.. Complexities of Genetic Counseling for ALS: A Case of Two Siblings with Discordant Genetic Test Results. J Genet Couns. 2015 Aug; 24(4):553-7. Accessed 8/5/2015.
Hanby MF et al.,. The risk to relatives of patients with sporadic amyotrophic lateral sclerosis. Brain. 2011 Dec; 134(12):3451–3454. Accessed 8/5/2015.
Steinberg KM, Yu B, Koboldt DC, Mardis ER, Pamphlett R. Exome sequencing of case-unaffected-parents trios reveals recessive and de novo genetic variants in sporadic ALS. Sci Rep. 2015 Mar; 16;5:9124. Accessed 8/5/2015.
Takahashi, Y et al.,. ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19. Am. J. Hum. Genet. 2013; 93:900-905. Accessed 8/5/2015.