Fragile X Syndrome

What Is It?

Fragile X syndrome is an inherited disorder associated with mental retardation and a particular appearance. It is caused by an error in a small piece of the DNA (genetic blueprint) for the FMR-1 gene. This gene is found on the X chromosome, one of the two chromosomes, X and Y, that determine gender.

In people with fragile X, a particular section of the DNA code CGG is "fragile" and gets repeated an unusually large number of times, compared with the normal 5 to 50 times. As a result, the FMR1 gene is not expressed (turned on), and the body cannot produce FMR1 protein, which is related to nerve function.

Depending on the number of CGG repetitions, fragile X can have a variety of physical, intellectual and behavioral effects. People with more repetitions tend to have more severe symptoms. For example, people with 200 or more CGG repetitions are described as having a full fragile X mutation and usually develop many of the symptoms of fragile X syndrome, including mental retardation. People with 50 to 200 CGG repetitions are described as having a fragile X premutation and may not show any obvious signs or symptoms of fragile X syndrome. The number of CGG repetitions can increase when the gene is passed from generation to generation, increasing the chance of developing the full fragile X mutation.

Fragile X syndrome is seen in approximately 1 in 4,000 to 6,000 males and 1 in 8,000 to 9,000 females. However, many more people carry the fragile X gene, either the full mutation or the premutation, but show no signs or symptoms of the syndrome. Fragile X syndrome is the most common inherited cause of mental retardation in males.

Symptoms

Signs and symptoms vary and can include:

• Elongated face; large, bulging ears; prominent chin and forehead; high arched palate (roof of the mouth); flat feet; large testicles in boys (especially after puberty)
• Other physical problems, including crossed eyes (strabismus), serous otitis media (fluid in the middle ear that is not infected), unusually flexible joints, seizures and mitral valve prolapse
• Cognitive and intellectual problems, including mental retardation, learning disabilities and abnormal speech
• Behavioral problems, including hyperactivity, attention difficulties, avoidance of eye contact and other autisticlike behaviors, violent outbursts (especially in teenage boys), and an unusual sensitivity to environmental stimuli such as sights, sounds, smells and touch

Fragile X tends to be milder and less obvious in females. A female normally inherits two X chromosomes, one from each parent. If one of the X chromosomes has the fragile X mutation, the other X chromosome, inherited from her unaffected parent, can partially compensate for the incorrect genetic information. About half of affected females show no symptoms of fragile X syndrome. The other half has symptoms, especially learning disabilities, behavioral problems or intellectual impairment.

In males, fragile X tends to be more obvious and more severe. A male child inherits only one X chromosome, from his mother. If that X chromosome has the fragile X mutation, the child most likely will have the full fragile X syndrome because the Y chromosome (inherited from his father) does not carry the genetic information that can compensate for the problem.

Diagnosis

The doctor may suspect that your child has fragile X syndrome based on your child's physical appearance and symptoms and a history of behavioral problems or learning difficulties at school. Your doctor also may ask about a family history of intellectual or behavioral problems.

Your doctor can confirm the presence of a fragile X premutation or mutation by taking a sample of blood and sending it for a DNA test that will identify the FMR-1 gene and count the number of CGG repetitions.

Expected Duration

Fragile X is an inherited genetic problem that is present at birth and lasts throughout life.

Prevention

There is no way to prevent fragile X syndrome. Affected people can have genetic testing and genetic counseling to get information about their risk of passing fragile X to their children.

Treatment

There is no way to correct or remove the extra CGG repetitions that cause fragile X syndrome. Treatment focuses on relieving symptoms and maximizing a child's potential. This can include:

• A special education program with modifications in classroom environment, teaching materials and curriculum
• Psychological counseling for the affected child and family
• Occupational therapy and speech-language therapy
• Medication to treat hyperactivity, attention difficulties, violent outbursts and other behavioral problems
• For adolescents and adults with mental impairment, vocational training and, if indicated, placement in a group home

When To Call A Professional

Call your doctor if you suspect that your child has fragile X syndrome that has not been diagnosed or if you have questions about your risk of having a child with fragile X syndrome. If you have a close relative who has been diagnosed with fragile X syndrome, or if several members of your family have unexplained mental impairment, ask your doctor whether you need to be tested for fragile X.

Prognosis

The outlook for children with fragile X syndrome is better when the disease is diagnosed early. Among people with a full fragile X mutation, about one-third of females and three-quarters of males have lifelong mental retardation. In most cases, this mental retardation is mild. People with fragile X syndrome usually have a normal lifespan.

Additional Info

National Institute of Child Health & Human Development

Building 31, Room 2A32

MSC 2425

31 Center Drive

Bethesda, MD 20892-2425

Toll-Free: 1-800-370-2943Fax: 301-496-7101

Email: nichdinformationresourcecenter@mail.nih.gov

http://www.nichd.nih.gov/

American Academy of Pediatrics (AAP)

141 Northwest Point Blvd.

Elk Grove Village, IL 60007-1098

Phone: 847-434-4000

Fax: 847-434-8000

Email: kidsdocs@aap.org

http://www.aap.org/

National Fragile X Foundation

P.O. Box 190488

San Francisco, CA 94119

Phone: 925-938-9300

Toll-Free: 1-800-688-8765

Fax: 925-938-9315

Email: natlfx@fragilex.org

http://www.nfxf.org/