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 FMR1 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 59 to 200 CGG repetitions are described as having a fragile X pre-mutation 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 pre-mutation, but show no signs or symptoms of the syndrome. Fragile X syndrome is the most common inherited cause of mental retardation in males.
Signs and symptoms vary and can include:
Large head, 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 imbalance of eye muscles (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 behaviors on the autism spectrum, 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 have symptoms, especially learning disabilities, behavioral problems or intellectual impairment.
In males, fragile X tends to be more obvious and more severe. A male child usually 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.
The pre-mutation can also increase the risk of two other disorders: fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS).
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. In young children, there may be no obvious physical symptoms, so the suspicion may be just based on developmental delays.
Your doctor can confirm the presence of a fragile X pre-mutation or mutation by taking a sample of blood and sending it for a DNA test that will count the number of CGG repetitions in the FMR1 gene.
Fragile X is an inherited genetic problem that is present at birth and lasts throughout life.
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.
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
Newer approaches to treatment are based on research studies that show changes in brain function related to FMR1 activity. Changes in the FMR1 gene change the way nerve cells "talk" to each other within the brain. Scientists are now studying medications that try to correct this communication breakdown.
When To Call A Professional
Any child with unexplained developmental delays should be tested for fragile X syndrome, because the symptoms are not very specific in young children. 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 you have family members with unexplained mental impairment, ask your doctor whether you need to be tested for fragile X.
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 half of females and almost all males have lifelong mental retardation. People with fragile X syndrome usually have a normal lifespan.
Fragile X carriers can have other symptoms. Among women with a permutation, 1 in 5 experiences premature ovarian failure. Among men and women with a permutation, there is an increased risk of another neurological problem called fragile X tremor-ataxia syndrome (FXTAS).
National Institute of Child Health & Human Development
Building 31, Room 2A32
31 Center Drive
Bethesda, MD 20892-2425
American Academy of Pediatrics (AAP)
141 Northwest Point Blvd.
Elk Grove Village, IL 60007-1098
National Fragile X Foundation
P.O. Box 190488
San Francisco, CA 94119