Genetics Northern California

Fragile X Syndrome

Fragile X syndrome is the most common form of inherited mental retardation. It is more common in males than in females and males are usually more severely affected. Fragile X syndrome occurs in approximately 1 in 2000 males and 1 in 4000 females. It is found in people from all parts of the world.

There is a range of intellectual ability in people with fragile X syndrome. Boys are usually more affected intellectually than girls. The majority of boys with fragile X syndrome will have mild to moderate mental retardation, although it can be severe. For girls, learning ability can range from normal intelligence to mental retardation.

Young children with fragile X syndrome usually look just like other children. As they grow older, boys in particular, can have physical features that do not look unusual but are frequently seen in fragile X syndrome. These features include long narrow face, large ears, prominent forehead, large jaw, large testes, double-jointed fingers, and flat feet.

Fragile X: Handout that describes fragile X syndrome and genetic testing for this condition. 

Cause
Fragile X syndrome is the result of a change in a gene. There are thousands of genes in each cell of the body and each provides important instructions to help the body grow and develop correctly. Genes are packaged into structures called chromosomes. Chromosomes come in pairs and one of each pair is inherited from your mother and the other from your father. One of the pairs of chromosomes, the X and Y chromosomes, determines whether a person is a male or a female. Males have an X and a Y chromosome and females have two X chromosomes.

The fragile X gene is located on the X chromosome. Normally, part of the gene is duplicated over and over, up to 50 times. If a person has less than 50 duplicated areas, also called repeats, the fragile X gene will work normally. In some families, however, the number of repeats can increase as the gene is passed down through generations. If the number of repeats increases to over 200, it is called a fragile X full mutation. A person with a fragile X full mutation is at risk to have the physical features and intellectual disabilities associated with fragile X syndrome. The increase in the number of repeats occurs gradually and usually does not increase to over 200 repeats in one generation. In fact, if a person has fewer than 50 repeats the gene is considered stable and is very unlikely to increase in size as it is passed down. There is an intermediate level of repeats, however, in which a person has between 50 and 200 repeats. This is called a fragile X premutation. If a woman carries a premutation, there is a chance the number of repeats will increase to over 200 as she passes the premutation on to her child. When a man is a premutation carrier, however, the number of repeats stays stable as it is passed on to his children. Therefore, a man with a premutation will not have a child with fragile X syndrome.

Because women have two X chromosomes, not all the children of a woman carrying a fragile X premutation will inherit the chromosome with the premutation. Each time she has a child there is a 50% chance that she will pass on the X chromosome without the premutation. In this case, her baby would not have a chance of having fragile X syndrome nor carry the premutation. People who carry a premutation for fragile X are usually unaffected but there is a tendency towards shyness or anxiety, as well as mild learning disabilities. Women who are premutation carriers also have about a 15% chance of having premature ovarian failure (menopause before the age of 40).

Testing and diagnosis

Testing for fragile X syndrome is done by a genetic test that counts the number of repeated areas found in the fragile X gene. It is a very accurate way of diagnosing the condition. Fragile X testing can also tell a woman if she has a premutation in the fragile X gene and therefore at an increased risk of having a baby with fragile X syndrome.

If a woman finds out that she is a premutation carrier for fragile X syndrome there is prenatal testing available that can tell her whether her baby has the condition. The most accurate test available is an amniocentesis and it is done when a woman is at least 14 weeks pregnant. There is another test, called chorionic villus sampling (CVS), which is done earlier in the pregnancy but has some limitations in the accuracy of predicting whether a baby will have fragile X syndrome. Because there are risks to the pregnancy related to having an amniocentesis or CVS, it is important for a pregnant woman to speak to a genetic counselor about her options and decide what is best for her and her family.

Treatment/Services
There is currently no cure for fragile X syndrome. Treatment is provided based on each child's individual needs. Many people with fragile X syndrome benefit from special education, which can help them to maximize their potential. Because children and teenagers with fragile X syndrome can have hyperactive behavior and a short attention span, parents may want to consider talking to their physician about the option of medication which may help their child to be more focused, particularly at school. Behavioral modification with positive reinforcement has also been found to be useful.

RESOURCES

For more information about Fragile X syndrome visit the National Fragile X Foundation website.