Fragile X Info Series
overview of fragile x syndrome and associated disorders
Fragile X is a group of conditions associated with changes in the Fragile X gene — called FMRl — 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. The range of 45–54 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:
FXS
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.
FXTAS
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.
FXPOI
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.
FEMALES AND FRAGILE X
Genetic counseling is recommended for any woman with a Fragile X premutation or full mutation. This can allow for discussion of pregnancy issues, and reproductive options including prenatal testing, use of egg donor or IVF, and other options.
Testing to determine whether a full mutation or premutation exists is recommended for any adult woman who may be at risk of being a premutation carrier. This includes women with a personal or family history of intellectual disability, FXS, FXTAS, or infertility.
OTHER PREMUTATION CONDITIONS
Other issues may be present in premutation carriers, and this is an ongoing area of study for researchers.
Females With a Full Mutation
Females with a full mutation exhibit a wide range of characteristics, though they usually have milder symptoms than males with a full mutation, and may not even know their status. This is because females have two X chromosomes (males have only one), and the unaffected X chromosome can often compensate to varying degrees for the one with the Fragile X mutation.
Women with a full mutation are not at risk for FXPOI and have no associated infertility.
PHYSICAL CHARACTERISTICS
Girls are much less likely than boys to exhibit physical characteristics of Fragile X. Many have no noticeable physical differences. Of those who do, the most common features are:
- Slightly prominent ears
- Highly flexible finger joints, wrists, or elbows
- Flat feet
COGNITIVE CHARACTERISTICS
Females with a full mutation range from having very mild to moderate learning difficulties. The most common challenges are in:
- Visual-spatial abilities like reading maps and graphs
- Executive functioning (the ability to formulate, execute, and carry out a plan)
- Mathematics
BEHAVIORAL CHARACTERISTICS
Females with a full mutation can exhibit behavioral or social challenges that include:
- Attention/concentration difficulties (or ADHD)
- Shyness or social anxiety
- Difficulty in picking up on “social cues”
EMOTIONAL ISSUES
Females with a full mutation are at increased risk to experience anxiety.
Mood swings and depression may be present — often most acutely during adolescence. Medication, counseling, and other interventions may help address these issues.
Consultations with family physicians and experts with experience in FXDs can be important in obtaining the assistance a person needs.
A small percentage of females who have the full mutation will have no apparent signs of the condition — physical, cognitive, behavioral, or emotional. These females are often identified only after another family member has been diagnosed.
Females with Premutation
Females with a premutation are at risk to have a child, male or female, with Fragile X syndrome. The magnitude of this risk is related to the number of CGG repeats identified in her FMRl gene. The larger the number, the higher the risk for expansion from a premutation to a full mutation if it is passed on.
Some women with a premutation have reported increased general anxiety, shyness, and social anxiety. In addition, there is evidence that women with the premutation are at increased risk for depression.
FXPOI
Approximately 20%-25% of women with a premutation experience FXPOI, which is characterized by infertility, decreased ovarian function, early menopause, or irregular cycles. (Note: Women with a full mutation are not at risk for FXPOI and have no associated infertility.)
FXTAS
FXTAS is another medical effect of the premutation. It is more common in male carriers, but has been reported in about 5%-8% of female carriers over the age of 50.
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Females and Fragile X
Characteristics of females with full mutation and premutation Fragile X.
How We Can Help
The NFXF is dedicated to serving the entire Fragile X community to live their best lives by providing the knowledge, resources, and tools, until, and even after more effective treatments and a cure are achieved. Learn more with Fragile X 101.
If you have questions please reach out to us at treatment@fragilex.org or call (800) 688-8765.
