Individuals with a family history of this disorder should consult a genetic counselor to learn more about the risks to their offspring.

• Normal number of repeats: Individuals with a normal number of repeats (6 to 45) cannot pass fragile X syndrome on to their offspring. The number of repeats in the offspring generally does not change.
• Intermediate number of repeats or “gray zone”: When an individual has more than about 45 repeats but fewer than 55 repeats, the number of repeats can sometimes expand slightly when passed from parent to child. Individuals who have between about 45 and 55 repeats are considered in a “gray zone.” These individuals have not been found to have a child with fragile X syndrome. However, the number of repeats can grow with each generation, so their grandchildren could be at risk (7).
• Pre-mutation: Individuals with between about 55 and 200 repeats have what is called a pre-mutation (7). Both men and women can be carriers of the pre-mutation. About 1 in 250 women and 1 in 800 men carries the pre-mutation (8). However, only women who carry the pre-mutation are at risk for having a child with fragile X syndrome.

  A pre-mutation carrier mother has a 50 percent chance of passing along the abnormal gene to her baby during each pregnancy. Some children who inherit the abnormal gene have a pre-mutation and no symptoms of fragile X syndrome. However, the number of repeats is likely to expand20when the gene is passed from mother to child. As a result, some children of carrier mothers inherit the full mutation (more than 200 repeats) and show symptoms of fragile X syndrome.

  A male pre-mutation carrier passes on the pre-mutation to all of his daughters but to none of his sons. The daughters generally have no symptoms of fragile X syndrome, but they are carriers of a pre-mutation that may be passed on to their children. Unlike in females, in males the pre-mutation does not usually expand in size when passed on to their daughters. Sons of men with the pre-mutation do not inherit it because they do not get an X chromosome from their father.

• Full mutation: Individuals with more than 200 repeats have the full mutation. A woman with a full fragile X mutation has a 50 percent chance of passing along the full mutation in each pregnancy. If a man with a full mutation has children, he will pass the pre-mutation on to all of his daughters. For reasons that are not understood, the full mutation shrinks back to a pre-mutation in sperm. His sons are not at risk because they do not inherit the X chromosome from their father.

Individuals with the pre-mutation do not have fragile X syndrome. However, recent studies suggest that some may have subtle behavioral or learning problems.

Recent studies also suggest that about 30 percent of males over age 50 with the pre-mutation develop a neurological disease consisting of tremor and uncoordinated muscle movement (7). A small number of women with the pre-mutation also may develop this disorder, though they tend to be older than affected men and have milder symptoms

In addition, about 20 percent of women with the pre-mutation develop ovarian failure and early menopause (before age 40), which can affect fertility (1, 7). Individuals with the full mutation generally do not develop the neurological disorder or ovarian failure.