Causes

Fragile X is caused by a mutation in the FMR-1 gene. Genes are chains of genetic material controlling inherited characteristics and there are very many on each chromosome. Genes provide the blueprint for the production of proteins.

Ordinarily the FMR-1 gene has up to 40 repeats of a sequence of DNA components called CGG. In a Fragile X pre-mutation there are up to 200 repeats of the CGG components. At the pre-mutation or carrier level the gene produces enough protein to work normally. However, when the number of repeats exceeds 200 (called a full mutation), the mutation interferes with the normal production of the protein produced by the FMR-1 gene. The absence of this protein appears to account for many of physical and behavioural characteristics associated with Fragile X.

The gene mutation can be transmitted from parent to child on the affected X chromosome. It appears to increase in size as it passes from generation to generation going eventually from a pre-mutation (between 40 and 200 repeats) to a full mutation (greater than 200 repeats).

Why is it more common in boys than girls?

The X chromosome is one of a pair that determines a child’s sex. A boy has one X chromosome (inherited from his mother) and one Y chromosome (inherited from his father) while a girl has two X chromosomes (one each inherited from her mother and father).

Where a girl has a full mutation on one X chromosome and one “good” X chromosome, it seems that the “good” chromosome compensates (to varying degrees) for the effect of the Fragile X mutation on the other one. In this way a woman or man may unknowingly carry and pass Fragile X on to the next generation.

Fragile X appears more common in boys as they are usually more affected by the gene mutation because they do not have a second X chromosome to compensate for the altered FMR-1 gene.

Men who are carriers of Fragile X do not usually show any symptoms of intellectual disability, but will pass the premutation on to their daughters. Such daughters will usually be neurotypical however their children are at risk of being affected by Fragile X.