“What is my risk for affected children?”
A fragile X premutation can be present in males or females. Carriers are found in all ethnic and racial groups. Premutation carriers do not have fragile X syndrome and often do not have any history of fragile X in their families.
The first thing to know about being a woman who is a fragile X carrier is that if the abnormal gene is passed to a child (50% chance), then the child is at risk of having fragile X syndrome. Because of this, one of the main questions that female fragile X premutation carriers have at some point after learning their carrier status is: what is my risk for of having a child with fragile X syndrome? How high or low that risk is for the child to have fragile X syndrome depends on different factors such as,
1). How many total CGG repeats the carrier has
2). How many AGG interruptions the carrier has
It has been shown that AGG interruptions provide stability to the gene and make it less likely for women to have an affected child when the mother has 55-90 CGG repeats (Nolin, et. al, 2014). For more information on AGG testing that is available, please contact your healthcare provider or genetic counselor for the Xpansion Interpreter® test.
For men who are fragile X carriers it is important to note that all daughters will be carriers, but they are very unlikely to have fragile X syndrome themselves. A carrier man’s sons will inherit the man’s Y chromosome which would have no impact on fragile X syndrome.
“How can being a carrier affect my health?”
Although most fragile X premutation carriers have normal health and intelligence, there is a higher chance that a premutation carrier can develop certain signs and symptoms. These signs and symptoms are in addition to the risk of having a child with fragile X syndrome.
Male fragile X premutation carriers have an increased chance of developing a neurological movement disorder later in life. This movement disorder is called fragile X-related tremor/ataxia syndrome or FXTAS and includes Parkinson’s like features. This condition gets worse over time.
Female fragile X premutation carriers have about a 20% chance of having problems with fertility (ovaries not working properly), and, like male premutation carriers but to a lesser degree, an increased chance of developing FXTAS later in life. Female premutation carriers sometimes can have health issues such as thyroid problems, autoimmune problems, anxiety or depression.
Research studies are currently being conducted to see what role, if any, the stabilizing interruption, AGG, plays in the development of signs or symptoms of being a fragile X carrier.
Fragile X intermediate or grey zone carriers
Fragile X intermediate carriers or grey zone carriers have an even smaller change in the fragile X gene and occurs in ~2-3% of the population. They do not have symptoms of fragile X nor are they clearly at risk for the health issues sometimes seen in premutation fragile X carriers.
Male and female intermediate fragile X carriers have the potential to pass a larger-sized fragile X premutation (but not a full fragile X mutation) to each child. If the larger mutation is in the premutation range, it could lead to health issues in adulthood and risk for a full fragile X mutation in future generations. Because of this, one of the main questions that intermediate fragile X carriers have is: What is the chance of passing a larger fragile X gene change to my children?
For more information on available testing to understand your personalized chance of passing a premutation gene to your offspring, please contact your healthcare provider or genetic counselor for the Xpansion Interpreter® test.