How Common is Fragile X Syndrome?
The Katkowski Family
There have been a number of studies aimed at determining the prevalence of FXS in males and females. Studies have been undertaken both in the “special needs” population and the general population. The agreed upon prevalence of FXS in males is approximately 1 in 3,600 to 4,000 and in females is approximately 1 in 4,000 to 6,000.
The reason it is lower in females is that, while all males with an FMR1 full mutation will have fragile X syndrome, some females with an FMR1 full mutation will not have behavioral, cognitive or physical features of FXS.
How Many Individuals are Carriers of the FMR1 Premutation?
According to a 2012 study by the CDC, the frequency of Fragile X premutation is as follows:
- 1 in 151 females, or about 1 million women in the United States.
- 1 in 468 males, or about 320,000 men in the United States.
These statistics are important because both men and women are at risk for having symptoms linked to Fragile X-associated Disorders.
- Women with a premutation reported their last menstrual cycle at an earlier age than women without a premutation (48 vs. 51 years).
- Men and women with a premutation were more than four times as likely to report dizziness or fainting as people without a premutation (18% vs. 4%). Men and women with a premutation were more than twice as likely to report numbness as people without a premutation (29% vs. 13%).
- Twenty-three percent of people with a premutation had a child with a disability.
- Twelve percent of people without a premutation had a child with a disability.
This study of 6,747 older adults in Wisconsin found 30 people with a change in the FMR1 gene. Based on this relatively small number of people, the results should be interpreted with caution. These findings may not reflect all people in the United States with an FMR1 premutation For example a large Israeli study found approximately 1/130 women were FMR1 carriers.
The Prevalence of FXTAS and FXPOI
- Studies report that approximately 1/3 (33%) of all men over 50 years of age with an FMR1 premutation will develop symptoms of FXTAS. Not all of these men will have symptoms that fulfill the diagnostic criteria for FXTAS, as some develop mild features that do not progress.
- Studies report approximately 5-8% of women over 50 years of age with an FMR1 premutation, will develop features of FXTAS, though females tend to have fewer and milder symptoms than men.
- Approximately 20-25% of women with an FMR1 premutation will develop FXPOI. FXPOI covers a range of ovarian difficulties including early menopause, irregular menstrual cycles, infertility, sub fertility and premature ovarian failure (cessation of menstrual periods prior to age 40)
How Common are Intermediate (Grey Area) Alleles?
Approximately 1 in 50 (2%) of individuals have an intermediate allele. There appear to be no clinical associations with intermediate alleles. Most intermediate alleles are stable and do not change over generations. In a small number of families intermediate alleles show some slight instability and can lead to a premutation in future generations. Individuals with an intermediate allele are not at risk for any for the FXDs or to have children with fragile X syndrome.
Based on the best available evidence:
- Approximately 1 million Americans carry the Fragile X mutation, including approximately 100,000 with fragile X syndrome, and are at risk for developing a Fragile X-associated Disorder.
- Approximately 1 in 3,600 to 4,000 males in the world are born with the full mutation for Fragile X.
Note: The vast majority of males with the full mutation will have fragile X syndrome.
- Approximately 1 in 4,000 to 6,000 females in the world are born with the full mutation for Fragile X.
Note: Approximately 50% of females with the full mutation will have some features of fragile X syndrome.
- Approximately 1 in 468 men in the world are carriers of the Fragile X premutation.
- Approximately 1 in 151 women in the world are carriers of the Fragile X premutation.