What Causes Fragile X Syndrome?

Fragile X syndrome is a common type of intellectual disability that affects cognitive function and causes learning deficits in individuals. Symptoms of fragile X can range in severity and may include difficulties in school, such as difficulties with math problems, learning or developmental disabilities, or cognitive function. Fragile X is one form of intellectual disability that also can affect physical appearance, resulting in some recognizable physical characteristics among individuals with fragile X syndrome, such as a narrow face, a large jaw, and soft skin. Fragile X is a genetic disorder, and weâ€™re breaking down the causes, risk factors, and diagnosis.

What Causes Fragile X Syndrome?

Fragile X is a genetic disorder, meaning it is caused by a gene mutation, specifically a mutation on the fragile X messenger ribonucleoprotein 1, referred to as FMR1.

Fragile X Messenger Ribonucleoprotein 1 (FMR1)

The FMR1 gene is normally found on the X chromosome, and is responsible for making a protein, called FMRP, that is important for creating and maintaining connections between cells in the brain and in the nervous system. The mutation causes the body to make a reduced amount, or none, of the FMRP protein, causing the physical and cognitive impairments known as Fragile X. Not everyone with a mutation in FMR1 will have the symptoms of fragile X because the body may still make a certain amount of FMRP.

A few things affect how much FMRP the body can make, which in turn affects the symptoms of fragile X. The size of the mutation is one thing that affects how much protein the body can make: Some people have a smaller mutation, meaning it repeats less on their FMR1 gene, which allows the body to still make some amount of FMRP. Producing some amount of this protein and having it in the body may make symptoms milder. The number of cells that have the mutation will also affect the amount of FMRP in the body, which in turn will affect the symptoms of fragile X. Since every cell in the body is not exactly the same, some cells may have a mutation in FMR1 while others may not. This is called mosaicism. If the mutation is present in most of the cells in the body, the person will likely have symptoms of Fragile X. If the mutation is present in only some of the cells, they will likely have fewer symptoms. An individualâ€™s gender will also affect the amount of FMRP in the body. Females have two X chromosomes, while males only have one. In females, if the FMR1 gene has the mutation on one X chromosome, the mutation may not be present on the other X chromosome, meaning there will be some production of FMRP and females will have milder symptoms.

Fragile X Syndrome Risk Factors

Fragile X syndrome is a genetic disorder, and the most common risk factor for developing fragile X is having a parent who carries the FMR1 mutation. Fragile X syndrome is much less common in females, due to the fact that females have two X chromosomes, while males only have one. As mentioned above, if the FMR1 gene has the mutation on one X chromosome, the mutation may not be present on the other X chromosome, meaning there will be some production of FMRP and females will have milder symptoms.

Is Fragile X Syndrome Inherited?

Fragile X syndrome can be inherited, but to understand the inheritance, it is important to understand the mutation itself and how it causes issues in the production of FMRP. In the FMR1 gene, there is the DNA pattern of the chemical letters, CGG, which is repeated over and over again. Different people have different numbers of these CGG repeats, but most people have fewer than 45 repeats. Individuals with FXS usually have more than 200 repeats, which causes the FMR1 gene to stop producing FMRP, resulting in the symptoms of FXS.

Most males will have anywhere from 5-44 repeats of CCG in their FMR1 gene, and most women will have anywhere from 5-44 repeats of CCG on each of their FMR1 genes. These individuals do not have FXS and will not pass FXS onto their children. Individuals with 45-54 repeats of CCG do not have FXS, but they may have a slightly higher chance of having fragile X related symptoms, and may possibly pass these symptoms onto their children.

Individuals with 55 to 200 repeats are said to have a premutation in the FMR1 gene; they do not have FXS but may be at risk for developing fragile X related syndromes in the future. In addition, people with a premutation can have children with a premutation or full mutation. Individuals with more than 200 repeats have FXS, and with each pregnancy, a woman with FXS has a 50% chance of passing on FXS to her children.

Can Fragile X Be Diagnosed During Pregnancy?

Since fragile X may be inherited, it is possible to test during pregnancy to determine if your baby will have fragile X. This testing could include amniocentesis or chorionic villus sampling. Prenatal testing can help families prepare for a baby with fragile X syndrome so they can start treatment as early as possible. But most parents donâ€™t know they carry the gene, so prenatal testing is uncommon.

Can Fragile X Syndrome Be Prevented?

Fragile X is a genetic syndrome that cannot be cured or prevented. If you are at high risk for having a child with fragile X, consulting a genetic counselor before getting pregnant can help you determine your chances of having a child with fragile X.