What is Fragile X Syndrome?
Fragile X Syndrome is the most common inherited cause of mental retardation. Although many of us have heard of Trisomy 21 or Down Syndrome as a cause of mental retardation, few of us are familiar with Fragile X Syndrome. The exact prevalence of Fragile X Syndrome is not certain, but is believed to occur in about 1 out of every 2000 boys and 1 out of 4000 girls. Some studies indicate that up to 6% of mentally retarded males may be found to have Fragile X Syndrome.
Because Fragile X Syndrome is inherited, it is important to understand a little bit about the genetics behind it. All women carry two X chromosomes, and all men carry one X and one Y chromosome. The X and Y chromosomes are the so-called sex chromosomes. Located on the X chromosome is a gene called FMR-1. This gene is necessary to produce a certain protein that helps the brain function normally.
In persons with Fragile X Syndrome, there is a defect in this gene. As a result the place where the gene is located on the X chromosome looks like it is about to break off, thus the name "Fragile X." In some people the gene is only partially defective, what is sometimes referred to as a pre- mutation, and these people are termed carriers. Both men and women can be carriers because both men and women have at least one X chromosome. If a man has a fully defective FMR-1 gene on his one X chromosome, then he will usually shows signs of the Fragile X syndrome, including mental retardation. If a woman has a fully defective FMR-1 gene on just one of her two X chromosomes, then she may have mild symptoms of the condition. It would be rare for a woman to have two fully defective genes because she would need one from each parent.
In addition to understanding about pre- and full mutations, it is also important to know that the FMR-1 gene can go from a pre-mutation to a full mutation with each passing generation as the area of the pre-mutation becomes more unstable. The gene becomes unstable during a certain type of cell division called meiosis that occurs in the ovary. Thus a woman who is a carrier of a pre- mutation in the FMR-1 gene can have a child with a full mutation. A full explanation of this phenomenon is beyond the scope of this article.
What are the symptoms of Fragile X Syndrome?
The symptoms are varied and again depend upon the person's gender and whether he or she has one or two fully defective FMR-1 genes. In general, Fragile X Syndrome should be suspected in any male with mental retardation. The classic description is of a male with mild to profound mental retardation, hand-flapping or biting, poor eye contact, large ears, a thickened nasal bridge, a large head in childhood and a prominent jaw and testes, especially notable after puberty.
Affected persons often have delays in speech development and a peculiar manner of speaking called "cluttering." This is described as short bursts of words with breaks in the flow and repetition of sounds, words, and phrases. Although children with Fragile X Syndrome understand normally, they often have a delay in expressive speech. Another aspect of speech in less severely affected children is difficulty staying on topic. This is called tangential speech. An example would be, "I went to the store to buy bread. I like bread. It is soft. My belly is soft. There's my belly. Where's your belly?" In more severely affected children, language may be completely lacking. Because of the language problems, these children are often seen by a speech therapist before the diagnosis of Fragile X Syndrome is made.
Other commonly associated findings with Fragile X Syndrome are autistic behaviors such as hand flapping, biting and poor eye contact mentioned above. Autism affects about 60% of patients with Fragile X Syndrome . Attention deficit disorder with hyperactivity (ADHD) is also common. Learning disabilities are especially notable in mathematics.
How is Fragile X diagnosed?
Fragile X Syndrome is diagnosed by a blood test that looks at the patient's chromosomes and especially at the X chromosome in the area of the FMR-1 gene. For any child with mental retardation of unknown cause, looking at the chromosomes (called karyotyping) may provide valuable information. However, karyotyping alone may not be sensitive enough to detect mutations to the FMR-1 gene. The test specifically for Fragile X Syndrome is a DNA molecular analysis for FMR-1 gene. If there is a family history of Fragile X Syndrome , then testing may be done prenatally.
Who should be tested?
Fragile X Syndrome testing should be considered in any child, especially males, with mild to severe mental retardation for which there is no identified cause, especially if he has behavioral problems such as autistic traits or attention deficit disorder with hyperactivity. Other candidates would be a child with a learning disability, especially in mathematics, and behavioral problems.
Once a child is diagnosed with Fragile X Syndrome , it is important for both parents to be counseled regarding the diagnosis. Either genetics counselor or a medical geneticist will be able to discuss the diagnosis and its implications. As part of the diagnosis, parents may want to consider getting themselves and their other children tested to determine carrier status. This is a personal decision which should be discussed with the genetics counselor or geneticist.
What treatments are available?
Because Fragile X Syndrome is a defect at the genetic level, at this time, there is no cure. Most education interventions are directed as the specific learning disability. Combined speech and occupational therapy is often used. For children with ADHD, a combination of behavioral modification techniques and medication may be useful. See the ADHD Treatment Guide for more information.
In addition to the affected child, the parents and siblings of an affected child may also benefit from getting involved with a support group.
Where else can I get information about Fragile X Syndrome?
The National Foundation for Fragile X maintains a web site at that serves to educate the public, medical professionals, and families about the condition. It is a national advocacy group that provides information packets, referrals, links to support groups and resources for families and other persons interested in Fragile X Syndrome.
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