Fragile X syndrome is characterized by moderate intellectual disability in affected males and mild intellectual disability in affected females. Distinctive physical features are sometimes present in affected males including a large head, long face, prominent forehead and chin, protruding ears, loose joints and large testes, but these features develop over time and may not be obvious until puberty. Motor and language delays are usually present but also become more apparent over time. Behavioral abnormalities including autistic behaviors are common.

Fragile X syndrome is caused by an abnormality (mutation) in the FMR1 gene. Affected individuals have an increased number of copies of a portion of the gene called CGG repeats. The greater the number of copies of CGG, the more likely there will be increased severity of the disorder. Fragile X syndrome occurs more often in males and results in more severe disease in males.

Mutations in the FMR1 gene are associated with two other conditions in addition to the fragile X syndrome (FXTAS and POI) and these conditions have been termed FMR1-Related Disorders. 

FXS can cause learning disabilities, developmental delays, and social or behavioral problems. Disabilities vary in severity. Boys with FXS usually have some level of intellectual disability. Girls may have some Intellectual disability or learning disability, or both, but many with fragile X syndrome will have normal intelligence. They might only be diagnosed with FXS if another family member is also diagnosed.

People with FXS may show a combination of the following symptoms as children and throughout life:

• developmental delays, such as taking longer than normal to sit, walk, or talk compared with other children of the same age
• stuttering
• intellectual and learning disabilities, like having trouble learning new skills
• general or social anxiety
• impulsiveness
• attention difficulties
• social issues, like not making eye contact with other people, disliking being touched, and trouble understanding body language
• hyperactivity
• seizures
• depression
• difficulty sleeping

Some people with FXS have physical abnormalities. These may include:

• a large forehead or ears, with a prominent jaw
• an elongated face
• protruding ears, forehead, and chin
• loose or flexible joints
• flat feet

FXS is caused by a defect in the FMR1 gene located on the X chromosome. The X chromosome is one of two types of sex chromosomes. The other is the Y chromosome. Women have two X chromosomes while men have one X chromosome and one Y chromosome.

The defect, or mutation, on the FMR1 gene prevents the gene from properly making a protein called the fragile X mental retardation 1 protein. This protein plays a role in the functioning of the nervous system. The exact function of the protein is not fully understood. A lack or shortage of this protein causes the symptoms characteristic of FXS.

FXS cannot be cured. Treatment is aimed at helping people with the condition learn key language and social skills. This may involve receiving extra help from teachers, therapists, family members, doctors, and coaches.

There may be services and other resources available in your community to help children learn important skills for proper development. If you’re in the United States, you can contact the National Fragile X Foundation at 800-688-8765 for more information regarding specialized therapy and educational plans.

Medications that are typically prescribed for behavior disorders, like attention deficit disorder (ADD) or anxiety, may be prescribed to treat the symptoms of FXS. Medications include:

• methylphenidate (Ritalin)
• guanfacine (Intuniv)
• clonidine (Catapres)
• selective serotonin reuptake inhibitor (SSRI), such as sertraline (Zoloft), escitalopram (Lexapro), duloxetine (Cymbalta), and paroxetine (Pail, Pexeva)

Being a fragile X permutation carrier can increase your risk for various medical conditions. Let your doctor know if you think you may be a carrier or if you have a child with FXS. That will help your doctor manage your care.

Women who are carriers are at an increased risk for premature menopause, or menopause that starts before the age of 40. Men who are carriers are at increased risk for a condition known as fragile X tremor ataxia syndrome (FXTAS). FXTAS causes a tremor that gets increasingly worse. It also can lead to difficulty with balance and walking. Male carriers may also be at an increased risk for dementia.