Fragile X Syndrome
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.
Prevalence of FXS and Autism Spectrum Disorder
Fragile X syndrome is the most common known single gene cause of ASD.
Children with FXS Who Also Have ASD
Many studies have evaluated the FXS-ASD link over the past decade. Since many children with FXS are interested in social interactions, they may not meet the diagnostic criteria for ASD, even though they exhibit some features of ASD such as poor eye contact, shyness, social anxiety, hand-flapping and sensory issues. Autism is much more common in boys with FXS than in girls with FXS. According to the CDC, a national parent survey found that 46% of males and 16% of females with FXS have been diagnosed or treated for ASD. The FORWARD Registry and Database tells us that 40% of individuals with FXS are diagnosed with ASD by their doctor in a Fragile X Clinic.
Children with ASD Who Also Have FXS
Studies show that individuals with FXS who have autism can have a more significant intellectual disability (lower IQ) than those with FXS who do not have autism.
About 10% of children with ASD are identified as having another genetic and chromosomal disorder, such as Fragile X syndrome. Given the possibility of a link, it is recommended that all children with ASD, both male and female, be referred for genetic evaluation and testing for FXS and any other genetic cause of ASD.
Individual Carriers of the FMR1 Premutation
- 1 in 151 females, or about 1 million women.
- 1 in 468 males, or about 320,000 men.
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%).
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.
Fragile X-Associated Primary Ovarian Insufficiency | FXPOI
FXPOI occurs in about 20-25% of adult female FMR1 premutation carriers. It has also been reported in teenagers who are carriers, though it is less common in that population.
About 2% (1 in 50) of women with ovarian insufficiency are found to have an FMR1 premutation, as do about 7% (1 in 15) of those with a personal and family history of ovarian insufficiency.
Fragile X–Associated Tremor/Ataxia Syndrome | FXTAS
Current estimates suggest that about 30-40% of male FMR1 premutation carriers over 50 years of age, within families already known to have someone with Fragile X, will ultimately exhibit some features of FXTAS.
This figure may be as low as 10-20% in the general population, since the majority of carriers have a premutation in the lower range of CGG repeats, where the occurrence of FXTAS appears to be reduced.
Though there are specific diagnostic criteria for FXTAS, some men may only exhibit some of the symptoms, and may not develop all of the cardinal features of the condition.
For men who are premutation carriers, the chance of developing core symptoms of FXTAS (tremor, problems with walking/balance) increases with age:
- Ages 50-59 the chance is about 17%.
- Ages 60-69 about 38%.
- Ages 70-79 about 47%.
- Over 80 years old, about 75% will develop symptoms of FXTAS.
Studies of females have found that about 8-16% of premutation carriers, within families already known to have someone with a Fragile X condition, develop some FXTAS symptoms. The symptoms in females tend to be milder.
FXTAS may be one of the most common adult onset, single-gene neurological diseases, similar in prevalence to other neurodegenerative diseases such as ALS (Lou Gehrig’s disease); however, more studies within the general population will be necessary before the true incidence is known.
Intermediate (Grey Area) Alleles
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 (all numbers approximate):
Americans carrying the Fragile X mutation:
- 1.5 Million
Americans carrying the Fragile X mutation + have Fragile X syndrome:
Born with the full mutation for Fragile X, worldwide:
- 1 in 3,600–4,000 Males1
- 1 in 4,000–6,000 Females2
1 The vast majority of males with the full mutation will have Fragile X syndrome.
2 50% of females with the full mutation will have some features of Fragile X syndrome.
Fragile X premutation carriers, worldwide:
- 1 in 468 Males
- 1 in 151 Females