What are the common symptoms?
Symptoms of fragile-X syndrome include:
mental impairment, ranging from learning disabilities to mental retardationattention deficit and hyperactivityanxiety and unstable moodautistic-like behaviorslong face, large ears, flat feet, andhyperextensible joints, especially fingers.
Boys are typically more severely affected than girls. While most boys have mental retardation, only one-third to one-half of girls has significant intellectual impairment; the rest have either normal IQ or learning disabilities. Emotional and behavioral problems are common in both sexes.
What Causes Fragile-X?
In 1991, scientists discovered the gene (called FMR1) that causes fragile-X. In individuals who have fragile-X syndrome, a defect in FMR1 (a "full mutation") shuts the gene down. Like a defective factory, FMR1 cannot manufacture the protein that it normally makes. Other individuals are carriers: they have a small defect in FMR1 (called a "premutation") but do not show symptoms of fragile-X.
Fragile-x is inherited. Carrier men (transmitting males) pass the premutation to all their daughters but none of their sons. Each child of a carrier woman has a 50% chance of inheriting the gene. The Fragile-x premutation can be passed silently down through generations in a family before a child is affected by the syndrome
Genetic Cause of Fragile-x
The FMR1 gene is located on the long arm of the X chromosome. Within this gene lies a region of DNA, which varies in length from one person to another. Ordinarily, this stretch of DNA falls within a range of length that would be considered "normal".
In some people, however, this stretch of DNA is somewhat longer; this gene change is called a "premutation". Although a person who carries the premutation does not typically has symptoms of Fragile-x, the stretch of DNA is prone to further expansion when it is passed from a woman to her children. When the stretch of DNA expands beyond a certain length, the gene is switched off and does not produce the protein that it is normally makes. This gene change is called a "full mutation".A male who inherits a full mutation exhibits characteristics of Fragile-x syndrome because his only X chromosome contains the mutated gene. A female may not be as severely affected as a male because each cell of her body needs to use only one of its two X chromosomes and randomly inactivates the other.
How is Fragile-x inherited?
Under normal circumstances, each cell in the body contains forty-six (twenty-three pairs of) chromosomes. These chromosomes consist of genetic material (DNA) necessary for the production of proteins, which lead to growth, development and physical/intellectual characteristics. The first twenty-two pairs of chromosomes are the same in males and females. The remaining two chromosomes are called the sex chromosomes (X and Y). The sex chromosomes determine whether a person is male or female.
Males have only one X chromosome, which is inherited from the mother at conception. They receive a Y chromosome from the father. Females inherit two X chromosomes, one from each parent.
How prevalent is Fragile-x in the general population?
Fragile-x syndrome is the single most common inherited cause of mental impairment. Recent studies suggest that Fragile-x affects 1 in 2000 males and 1 in 4000 females of all races and ethnic groups. (Bailey, D.B., and Nelson, D. 1995. The nature and consequences of Fragile-x syndrome. Mental Retardation and Developmental Disabilities Research Reviews 1: 238-244.). Studies also indicate that about 1 in 259 women of all races carry Fragile-x and could pass it to their children. The number of men who are carriers is thought to be 1 in 800.
Large-scale population studies of the incidence of Fragile-x still need to be done, but these extremely high prevalence statistics make it clear that Fragile-x is one of the most common genetic diseases in humans. 80-90% of people with Fragile-x are not yet correctly:
