National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Amyotrophic lateral sclerosis

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What are the chances of passing on sporadic ALS to offspring? Are there cases where a sporadic case became the first of an autosomal dominant inheritance?

The following information may help to address your question:


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.[1] 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.[2]
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 dominant gene mutations in people with ALS.[3][4] 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 conception.

These research findings, and rare case reports, support that this is possible.[3][4] It is common for these mutations to be very unique to a family, and so very little is often known about the specific mutation.[3] Factors such as "reduced penetrance" have also been reported in these cases, making it very difficult to predict if a person will develop ALS.[4] 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.

The Clinical Research in Amyotrophic Lateral Sclerosis and Related Disorders for Therapeutic Development (CREATE) Consortium is an integrated group of academic medical centers, patient support organizations, and clinical research resources dedicated to conducting clinical research, including genetic studies, involving sporadic and familial forms of amyotrophic lateral sclerosis. The CREATE Consortium has a contact registry for patients who wish to be contacted about clinical research opportunities and updates on the progress of the research projects.
Last updated: 8/5/2015

We hope this information is helpful. We strongly recommend you discuss this information with your doctor. If you still have questions, please contact us.

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GARD Information Specialist

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  1. 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.
  2. 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.
  3. 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.
  4. 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.