Definition

Fragile X syndrome (FXS) is a problem of the X chromosome. It is a condition that is inherited from the parents. FXS is the most common cause of inherited intellectual disability.

Causes

FXS is caused by problems with the FMR1 gene. These problems prevent fragile X mental retardation protein (FMRP) from developing. The protein helps to make connections in the brain. Without the protein, certain connections in the brain cannot be made. This causes developmental problems and prevents children from fully developing some higher cognitive functions.

Risk Factors

The main risk factor for FXS is having a parent with an FMR1 mutation. Most people who inherit a minor mutation, which is sometimes called a premutation, do not develop the symptoms and signs of FXS. A few premutated children may show signs that resemble autism. Others, primarily males, may develop a set of neurological symptoms called fragile X tremor ataxia syndrome in later adult life.

Children of mothers with FMR1 premutations are at risk of inheriting a fully mutated FMR1 gene severe enough to cause symptomatic FXS. If a woman does not have symptoms and is a carrier of an FMR1 mutation or premutation, each child of hers has a 50% chance of inheriting that gene. Of the children that inherit that gene, boys are much more likely to develop symptoms than girls. The severity of the disorder may vary between different individuals.

In general, each generation tends to have worse mutations and a higher risk of FXS than the previous one.

Symptoms

The number and severity of symptoms varies widely. Symptoms tend to be less frequent and milder in females. Symptoms can include:

• Mental impairment ranging from learning disabilities to intellectual disability
• Behavioral difficulties, including:
  • Attention deficit hyperactivity disorder (ADHD)
  • Anxiety
  • Unstable moods and emotional outbursts
  • Hypersensitivity to loud noises or bright lights
  • Aggressive behavior
  • Extreme shyness, particularly in girls
• Autistic behaviors
• Physical problems and abnormalities, including:
  • Long face with protruding jaw
  • Large, protruding ears
  • Flat feet
  • Hyperextended joints
  • High-pitched voice and enlarged testes in males after puberty
  • Mitral valve prolapse
  • Seizures
  • Low muscle tone and delayed motor skills such as sitting and walking

Diagnosis

The doctor will ask about symptoms and medical history. A physical exam will be done. FXS may be suspected if a child has:

• Physical, cognitive, or emotional symptoms of FXS
• Unexplained developmental delays or intellectual disability

The diagnosis can be confirmed by genetic testing with a DNA blood test.

Treatment

There is no cure for FXS. Treatment is aimed at controlling symptoms. Treatment may include:

Prevention

There are no known ways to prevent FXS once a person is born. If you have FXS or risk factors for FXS, you can talk to a genetic counselor when deciding to have children.

The National Fragile X Foundation http://www.fragilex.org

Sick Kids—The Hospital for Sick Children http://www.sickkids.ca

Committee on Genetics health supervision for children with fragile X syndrome. Pediatrics. 2011;127;994.

Fragile X syndrome. EBSCO DynaMed website. Available at:
http://www.ebscohost.com/dynamed
Updated February 19, 2013. Accessed June 24, 2013.

Fragile X syndrome overview. National Institute of Child Health and Human Development website. Available at:
http://www.nichd.nih.gov/health/topics/fragilex/Pages/default.aspx
Updated April 3, 2013. Accessed June 24, 2013.

What is fragile X? FRAXA Research Foundation website. Available at:
http://www.fraxa.org/fragilex
Accessed June 24, 2013.

Willemsen R, Anar B, De Diego Otero Y, et al. Noninvasive test for fragile X syndrome, using hair root analysis. Am J Hum Genet. 1999;65(1):98-103.