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What Health Problems Can Affect People Who Have a Fragile X Premutation?

People with premutation FMR1 genes do not have FXS. However, sometimes they have other symptoms, such as the following nervous system disorders, infertility, and problems with learning and behavior.

• Fragile X-Associated Tremor / Ataxia Syndrome (FXTAS)
  FXTAS is a disorder of the nervous system that leads to tremors, problems with walking and balance (called ataxia), memory loss, and mood disorders. Studies have shown that at least 30% of men with the premutation who are older than 50 years of age develop FXTAS. Women who have a premutation are less likely to be affected by FXTAS, but if they develop FXTAS, it happens at a later age than in men.
• Premature Ovarian Failure (POF)
  Normally, women will stop having menstrual cycles and experience menopause around 51 years of age. Women with premature ovarian failure (POF) stop having menstrual cycles and have symptoms of menopause before 40 years of age. POF occurs in about 1% to 4% of women in the general population; however, it occurs in about 22% of women who have a premutation for FXS. Therefore, women who carry a premutation are at risk for fertility problems in addition to the risk of having children who have FXS. Women who have a full mutation for FXS have the same risk for POF as women in the general population.
• Problems with learning and behavior
  The effects on learning and behavior in men and women with the FMR1 premutation are unclear. Women with the premutation might be more likely to have mood disorders and learning disabilities. Behavioral issues such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs) might also be more common than in the general population. However, more studies need to be done to look at the relationship between the premutation and learning and behavioral effects.

Why do people with premutations have symptoms that are different than those in FXS?

In people who have FXS, the FMR1 gene has a very large number of CGG repeats, which causes the gene to be turned off. As a result, there is no protein made. FXS is the result of the lack of a specific protein.

People with premutations do not have FXS because they still make some of the protein from the FMR1 gene. However, the premutation can affect how the gene works. Genes contain the recipes for proteins. Before the protein is made, a temporary copy of the gene is created. This temporary copy is made of RNA, a chemical very similar to DNA. In FMR1 genes with a premutation repeat, the gene makes extra RNA. The extra RNA affects how some cells work, which causes the symptoms described previously. Scientists do not yet understand exactly how the extra RNA causes these health problems.