Fragile X syndrome (FXS) is the most common known cause of mental retardation and developmental disability that can be inherited (passed from one generation to the next). The exact number of people who have FXS is unknown, but it is estimated that about 1 in 4000 males and 1 in 6000 to 8000 females have the disorder. Although FXS occurs in both males and females, females generally have milder symptoms. Signs that a child has FXS include not sitting, walking, or talking as early as other children. This is known as having developmental delays. Often, there are other physical and behavioral signs, but features of FXS vary and signs can be subtle and easy to miss. Children often have a typical facial appearance that gets more noticeable with age. These features include a large head, long face, and prominent ears, chin, and forehead. Children who have FXS might also have learning disabilities, speech and language delays, and behavioral problems such as attention-deficit/hyperactivity disorder (ADHD). Males who have FXS usually have some degree of mental retardation that can range from mild to severe. Females with FXS can have normal intelligence or some degree of mental retardation with or without learning disabilities. Autism-spectrum disorders (ASDs) also occur more frequently in children with FXS.
Causes
FXS is caused by mutations of the FMR1 gene. These mutations interfere with the normal development of certain parts of the brain and body by affecting the production of a normal body substance called “fragile X mental retardation protein” (FMRP). In the absence of FMRP, neural connections in the brain cannot be made properly, and affected children do not fully develop some higher cognitive functions.
Risk Factors
A risk factor is something that increases your chance of getting a disease or condition.
The main risk factor for FXS is having a parent with an FMR1 mutation. These mutations vary in degree. Most people who inherit a minor mutation, which is sometimes called a premutation, do not develop the symptoms and signs of FXS, though a few permutated children may show signs resembling autism, and others (primarily males) may develop a set of neurological symptoms called “fragile X tremor ataxia syndrome” in later adult life.
However, 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 is an asymptomatic carrier of an FMRI 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, although the severity of the disorder may be quite variable between different individuals.
In general, each subsequent 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:
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Mental impairment ranging from learning disabilities to mental retardation
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Behavioral difficulties, including:
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Autistic behaviors
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Physical problems and abnormalities, including:
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Diagnosis
The doctor will ask about symptoms and medical history, and perform a physical exam. FXS may be suspected if a child has:
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Physical, cognitive, or emotional symptoms of FXS
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Unexplained developmental delays or mental retardation
The diagnosis can be confirmed by a DNA blood test or, increasingly, by direct analysis of FMRP in hair or blood.
Treatment
There is no cure for FXS. Treatment is aimed at controlling symptoms. Treatment may include:
Medication
Medications used to treat symptoms of FXS include:
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Stimulants (such as Ritalin) and other medications to treat hyperactive behavior
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Psychotherapeutic drugs (such as Prozac) to help control:
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Anticonvulsants (such as carbamazepine) to control seizures
Scientists are currently trying to understand how FMRP works in the body so that specific treatments may someday prove possible. Unfortunately even the possibility of such treatment remains far in the future.
Educational Strategies
Specific educational strategies depend on the degree of developmental delays and/or mental retardation. Educational strategies include setting a stable educational environment for the patient that includes:
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School work that only requires a short attention span
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Minimal distractions
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Predictable activities and classroom routine
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Close communication between parent and school
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Emphasis on functional life skills
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.
RESOURCES:
FRAXA Research Foundation
http://www.fraxa.org
The National Fragile X Foundation
http://www.nfxf.org
National Institute of Child Health and Human Development
http://www.nichd.nih.gov
References:
American College of Medical Genetics website. Available at: http://www.acmg.net/.
Bardoni B, Davidovic L, Bensaid M, Khandjian EW. The fragile X syndrome: exploring its molecular basis and seeking a treatment. Expert Rev Mol Med. 2006;8(8):1-16.
FRAXA Research Foundation website. Available at: http://www.fraxa.org.
The Merck Manual of Medical Information. Simon and Schuster, Inc.; 2000.
National Institute of Child Health and Human Development website. Available at: http://www.nichd.nih.gov.
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.
CDC
