Fragile FX Syndrome

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Thanks to the National Fragile X Foundation Website for the following information (www.fragilex.org).

GENERAL FEATURES

FRAGILE X SYNDROME is a hereditary condition which can cause learning problems in both males and females. Fragile X Syndrome is the most common inherited cause of mental retardation. The full mutation appears in approximately 1 in 2000 males and 1 in 4000 females.

It is important to understand that Fragile X is a spectrum disorder. This means that there is a broad range of possible symptoms observed across cognitive, physical and behavioral features and that each person has a unique set of these features.

The majority of males with Fragile X Syndrome will have a significant intellectual disability. The spectrum ranges from subtle learning disabilities to severe mental retardation. Sometimes autism may be present.

The characteristics seen in males are also present in some females with Fragile X Syndrome. However, a smaller percentage of the females are affected and the degree of impact is usually diminished. This is because females have two X chromosomes and males only one. As a result, males with Fragile X have only the nonfunctioning gene; females with Fragile X have a normally functioning gene to partially compensate for the nonfunctioning gene.

Only about a third of the females have a significant intellectual disability. Others may have more moderate learning difficulties. Similarly, the physical and behavioral features seen in males, appear in a smaller percentage of females and often to a lesser degree.

In addition to mental impairment, Fragile X Syndrome is associated with a group of physical and behavioral characteristics as well as speech and language delays.

Physical features such as enlarged ears, long face with prominent chin, and large testicles are common but often these features do not appear until after puberty. Connective tissue problems may lead to ear infections, flat feet, double-jointed fingers and a variety of skeletal problems.

Behavioral characteristics in some males include attention deficit disorders, speech disturbances, hand biting, hand flapping, autistic behaviors, poor eye contact, and aversion to touch and noise.

CAUSE

A person with Fragile X Syndrome has a mutation in the FMR1 (Fragile X mental retardation 1) gene in the DNA that makes up the X chromosome. That mutation causes the cell to methylate a regulatory region of the FMR1 gene. The methylation turns off the FMR1 gene. Since the gene is turned off, the person doesn't make Fragile X mental retardation protein (FMRP). That lack of a specific protein triggers Fragile X Syndrome.

TREATMENT

At this time, there is no cure for Fragile X Syndrome. However, special education, speech and language therapy, occupational therapy and behavioral therapies are helpful in addressing many of the physical, behavioral, and cognitive impacts of Fragile X Syndrome. In addition, medical intervention can be helpful for aggression, anxiety, hyperactivity and poor attention span. Because the impact of Fragile X is so varied, it is important to do a careful evaluation of a person's strengths and weaknesses. That way, it is possible to tailor a treatment plan to address specific needs.

TESTING

During the 1980's and 90's, the only test available for diagnosing Fragile X syndrome was the chromosomal or cytogenetic test. While it was helpful, it was not always accurate. In the 1990's, two molecular DNA tests became available.

The Southern Blot analysis will show if the gene is a full mutation, the size of the full mutation, if the regulatory site has been methylated and if there is mosaicism
The polymerase chain reaction (PCR) analysis can determine the actual size of the repeat section in individuals with the stable version or with the premutation.

For more information check out www.fragilex.org or www.fraxa.org