Scleroderma and Genetics

By Alan W. Friedman, M.D., University of Texas/Houston, Health Science Center, Dept. of Internal Medicine/Rheumatology (originally published in Scleroderma Voice, 2001 #4)

Question: I am looking for answers as to whether there is a genetic/hereditary component to scleroderma. My 66-year-old husband died from CREST last year. I have a 37-year-old son, so of course I am concerned about the chance scleroderma could be inherited by him.

Answer: While scleroderma has generally been considered to be a disease that is not inherited, our studies at the University of Texas Houston Medical School suggest this is incorrect.

We have a very large database of scleroderma patients on whom we have complete genetic and clinical data, and the frequency of scleroderma in some member of their family (first-degree relative—meaning parent, brother, or sister) is roughly 1.5%.

This is far greater than the frequency in the general population (approximately 30 per 100,000 or 0.003%), which is strong evidence that this is either due to genetic transmission or a common environmental cause. There are really no hints that our patients had an unusual environmental exposure, which leaves genetics as the common factor.

We have also studied the Choctaw Indians in southeastern Oklahoma, where those who are full-blooded (no non-Choctaw blood going back as far as their records can go) have a frequency of scleroderma of 469 individuals per 100,000 (over 15 times the rate of the general population). This is also very strong evidence for a genetic effect, and extensive evaluations for an environmental cause have been unrevealing.

With regard to your son, our studies suggest that people with a family history of scleroderma have a risk of developing the disease that is 10–16 times higher than normal, but this is still quite low since scleroderma is a relatively rare disease.