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. 2011 Dec;134(Pt 12):3454-7.
doi: 10.1093/brain/awr248. Epub 2011 Sep 20.

The risk to relatives of patients with sporadic amyotrophic lateral sclerosis

Martha F Hanby  1 , Kirsten M Scott, William Scotton, Lokesh Wijesekera, Thomas Mole, Catherine E Ellis, P Nigel Leigh, Christopher E Shaw, Ammar Al-Chalabi
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The risk to relatives of patients with sporadic amyotrophic lateral sclerosis

Martha F Hanby et al. Brain. 2011 Dec.

Abstract

Amyotrophic lateral sclerosis is a neurodegenerative disease of motor neurons with a median survival of 2 years. Most patients have no family history of amyotrophic lateral sclerosis, but current understanding of such diseases suggests there should be an increased risk to relatives. Furthermore, it is a common question to be asked by patients and relatives in clinic. We therefore set out to determine the risk of amyotrophic lateral sclerosis to first degree relatives of patients with sporadic amyotrophic lateral sclerosis attending a specialist clinic. Case records of patients with sporadic amyotrophic lateral sclerosis seen at a tertiary referral centre over a 16-year period were reviewed, and pedigree structures extracted. All individuals who had originally presented with sporadic amyotrophic lateral sclerosis, but who subsequently had an affected first degree relative, were identified. Calculations were age-adjusted using clinic population demographics. Probands (n = 1502), full siblings (n = 1622) and full offspring (n = 1545) were identified. Eight of the siblings and 18 offspring had developed amyotrophic lateral sclerosis. The unadjusted risk of amyotrophic lateral sclerosis over the observation period was 0.5% for siblings and 1.0% for offspring. Age information was available for 476 siblings and 824 offspring. For this subset, the crude incidence of amyotrophic lateral sclerosis was 0.11% per year (0.05-0.21%) in siblings and 0.11% per year (0.06-0.19%) in offspring, and the clinic age-adjusted incidence rate was 0.12% per year (0.04-0.21%) in siblings. By age 85, siblings were found to have an 8-fold increased risk of amyotrophic lateral sclerosis, in comparison to the background population. In practice, this means the risk of remaining unaffected by age 85 dropped from 99.7% to 97.6%. Relatives of people with sporadic amyotrophic lateral sclerosis have a small but definite increased risk of being affected.

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Figures

Figure 1
Figure 1
Proportion of siblings remaining unaffected in the clinic population compared with the background population risk. Siblings represented by black line with 95% confidence limits as thinner dashed lines. Risk to local population shown by upper grey line. Note the Y axis starts at 0.95, not zero.
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