Fragile X Info Series
Fragile X is a group of conditions associated with changes in the Fragile X gene — called “FMRl” and located on the X chromosome. The FMRl gene can undergo changes, when inherited, which affects a pattern of DNA called CGG repeats. Typically, the FMRl gene has up to 54 CGG repeats, and the range between 45 and 54 repeats is called the intermediate or “gray zone.” A premutation carrier has 55–200 CGG repeats, and someone with a full mutation has more than 200 CGG repeats.
When a premutation or full mutation is present, it can result in a Fragile X-associated disorder (FXD). These include:
FRAGILE X SYNDROME
FXS is a condition affecting intellectual, behavioral, and social development. It occurs in both males and females who have a full mutation of the FMRl gene.
FRAGILE X-ASSOCIATED PRIMARY OVARIAN INSUFFICIENCY
FXPOI is a condition affecting ovarian function that can lead to infertility and early menopause in some female premutation carriers.
FRAGILE X-ASSOCIATED TREMOR/ATAXIA SYNDROME
FXTAS is an adult onset (over 50 years of age) neurological condition, seen in males and females, but more common and more severe in some male premutation carriers. It can cause tremors, memory, and balance issues.
OTHER PREMUTATION CONDITIONS
Other issues may be present in premutation carriers, and this is an ongoing area of study for researchers.
- Women with a premutation, on average, experience natural menopause at an earlier age compared to those without a premutation — the mean age of natural menopause being reduced by about 5 years from the typical age of about 51 years.
- Early estrogen deficiency is a consequence of POI. Symptoms of estrogen deficiency include hot flashes/flushes, night sweats, and vaginal dryness.
- Estrogen deficiency also leads to reduced bone mineral density, osteoporosis, a higher risk for earlier-onset cardiovascular disease, and dementia.
- A woman with a premutation may experience co-occurring conditions with FXPOI. More evidence is required to determine whether the following conditions are experienced at a higher frequency among women with a premutation: thyroid disorders, depression, anxiety, fibromyalgia, migraine headaches, and hypertension.
Risk for FXPOI
- Not all women with a premutation experience FXPOI, though all premutation carriers have at least a small increased risk above that found in the general population.
- One well-documented risk factor is the premutation repeat size: the highest risk for ovarian dysfunction is for women carrying premutation alleles in the 80–100 CGG repeat range.