Fragile X 101

What is Fragile X Syndrome?

Fragile X syndrome (FXS) is a genetic condition that causes intellectual disability, behavioral and learning challenges, and various physical characteristics. Though FXS occurs in both genders, males are more frequently affected than females, and generally with greater severity.

The reason it’s 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.

Life Expectancy

Life expectancy is not affected in people with FXS because there are usually no life-threatening health concerns associated with the condition.

Prevalence

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:

• Males — approximately 1 in 3,600 to 4,000.
• Females — approximately 1 in 4,000 to 6,000.

Signs & Symptoms

In Males

Behavioral characteristics

Behavioral characteristics can include:

• ADD/ADHD
• Autism spectrum disorder and autistic behaviors
• Social anxiety
• Hand-biting and/or flapping
• Poor eye contact
• Sensory disorders
• Increased risk for aggression

Intellectual disabilities

Intellectual disabilities in FXS include a range from moderate learning disabilities to more severe intellectual disabilities. The majority of males with Fragile X syndrome demonstrate significant intellectual disability.

Physical features

No one individual will have all the features of FXS, and some features, such as a long face and macroorchidism, are more common after puberty.

Physical features may include:

• Large ears
• Long face
• Soft skin
• Large testicles (called “macroorchidism”) in post-pubertal males

Connective tissue problems

Connective tissue problems may include:

• Ear infections
• Flat feet
• High arched palate
• Double-jointed fingers
• Hyper-flexible joints

Disposition

Disposition characteristics include:

• Very social and friendly
• Excellent imitation skills
• Strong visual memory/long-term memory
• Nice, like to help others
• Thoughtful
• Wonderful sense of humor

In Females

Behavioral characteristics

Behavioral characteristics seen in males can also be seen in females, though females often have milder intellectual disability and a milder presentation of the syndrome’s behavioral and physical features.

Intellectual disabilities

About one-third of females with FXS have a significant intellectual disability. Others may have:

• Moderate or mild learning disabilities
• Emotional/mental health issues
• General anxiety
• Social anxiety

A small percentage of females who have the full mutation of the FMR1 gene that causes FXS will have no apparent signs of the condition—intellectual, behavioral, or physical. These females are often identified only after another family member has been diagnosed.

The 3 Main Fragile X Disorders

Full mutation of the FMR1 gene (> 200 CGG repeats)

1. Fragile X Syndrome

Symptoms include intellectual disability, behavioral and learning challenges, and various physical characteristics. Males are more frequently affected, and generally with greater severity.

Premutation of the FMR1 gene (55–200 CGG repeats)

Traditionally, a carrier of a genetic mutation is defined as a person who inherits an altered form of a gene but shows no effects of that mutation. However, in Fragile X this definition does not exactly fit as carriers of a Fragile X premutation are at risk to develop FXTAS and FXPOI.

2. FXTAS — Fragile X-Associated Tremor/Ataxia Syndrome

Premutation carriers of an FMR1 gene mutation can have no apparent signs of a Fragile X disorder, and may or may not develop FXTAS (pronounced: FAKS-taz), which usually occurs in male premutation carriers after age 50, with symptoms — including balance, tremor, and memory problems — worsening with age.
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3. FXPOI — Fragile X-Associated Primary Ovarian Insufficiency

Premutation carriers of an FMR1 gene mutation can have no apparent signs of a Fragile X disorder, and may or may not develop FXPOI (pronounced: FAKS-poi), which usually occurs in female premutation carriers after age 40, and refers to a spectrum of impaired ovarian functions that can include infertility and early menopause.
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Genetics & Inheritance

Fragile X-associated disorders include a wide range of physical, intellectual, and behavioral symptoms that can affect family members in many different ways. These conditions are passed down in families through expansions of the FMR1 gene. Even for genetics professionals, FMR1 inheritance is complex and confusing, so it’s no surprise that families often have questions about the genetics of Fragile X. We start with some background on genetics and chromosomes …

Testing & Diagnosis

Who should be tested, lab tests for Fragile X including testing costs and reporting time, and other tests for children with developmental delay.

Premutation Carriers

When you or a family member are told you are a “carrier” for a Fragile X mutation, many questions arise.

31 Shareable Fragile X Facts

For National Fragile X Awareness Month, we share one fact a day for each day of the month, which we’ve also collected here.