Fragile X Carriers
Some individuals can be a ‘carrier’ of Fragile X Syndrome, meaning they can pass on the altered gene responsible for Fragile X to future generations. They are described as having a ‘premutation’ of Fragile X.
Fragile X Premutation
Large alterations to the FMR1 gene (over 200 CGG repeats) cause Fragile X Syndrome. However, some people have small alterations to this gene (55-200 repeats) and those with this version of the gene are described as being carriers or having a premutation. Approximately 1 in 250 females and 1 in 800 males are carriers.
There is a growing realisation that although this small alteration is not enough to ‘switch off’ the gene (like in Fragile X Syndrome), these smaller changes are important.
Firstly, the small alteration to the FMR1 gene makes it ‘unstable’. This means that it might change size when it is passed to the next generation, which can result in Fragile X Syndrome. All known cases of Fragile X Syndrome have been caused when the carrier gene has expanded when being passed from a mother to her child. Fathers pass X chromosomes (where the FMR1 gene is located) to their daughters, however there are no known cases where the gene has expanded to cause Fragile X Syndrome when passed from father to daughter. You can find out more about the inheritance of Fragile X in our resources.
Premutation Associated Conditions
In addition, some carriers will experience Fragile X Premutation Associated Conditions (FXPAC). These include:
Fragile X-Associated Tremor / Ataxia Syndrome (FXTAS): a degenerative neurological condition which onsets later in life.
Fragile X-Associated Primary Ovarian Insufficiency (FXPOI): a condition affecting women under the age of 40 where ovaries are not functioning at full capacity, which may lead to symptoms similar to the menopause.
There is some evidence that carriers may be more predisposed to experiencing particular mental health, physical health and cognitive characteristics or challenges. Fragile X testing should also be considered for women experiencing Fragile X-associated primary ovarian insufficiency or early menopause and for those (particularly men) in later life experiencing Parkinson's-like symptoms (tremor, ataxia or cognitive decline).