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Diseases

Genetic and Rare Diseases Information Center (GARD)

Other Names for this Disease
  • Fra(X) syndrome
  • FRAXA syndrome
  • FXS
  • Marker X syndrome
  • Martin-Bell syndrome
More Names
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Your Question

My daughter's father's sister had a son with fragile X syndrome. We are concerned about whether the gene was carried by her father and may have been passed down to her. Should my daughter be concerned about this before she starts a family?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What causes fragile X syndrome?

Mutations (changes) in the FMR1 gene cause fragile X syndrome. This gene carries instructions to make a protein called the fragile X mental retardation 1 protein. In most cases of fragile X syndrome, a specific DNA segment, known as the CGG triplet repeat, is expanded within the FMR1 gene. Normally, this DNA segment is repeated from 5 to about 40 times. In people with fragile X syndrome, however, the CGG segment is repeated more than 200 times. The abnormally expanded CGG segment turns off (silences) the FMR1 gene, which in turn disrupts nervous system functions and leads to the signs and symptoms of fragile X syndrome. In a small percentage of cases, other types of mutations cause fragile X syndrome. These mutations delete part or all of the FMR1 gene, or change one of the building blocks (amino acids) used to make the gene's protein. As a result, no protein is produced, or the protein's function is impaired because its size or shape is altered.[1]

Males and females with 55 to 200 repeats of the CGG segment are said to have an FMR1 gene premutation. Most people with a premutation are intellectually normal. In some cases, however, individuals with a premutation have lower than normal amounts of the fragile X mental retardation 1 protein. As a result, they may have mild versions of the physical features seen in fragile X syndrome (such as prominent ears) and may experience emotional problems such as anxiety or depression. Some children with a premutation may have learning disabilities or autistic-like behavior. About 20 percent of women with a premutation have premature ovarian failure, in which menstrual periods stop by age 40. Men, and some women, with a premutation have an increased risk of developing a disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). This disorder is characterized by progressive problems with movement (ataxia), tremor, memory loss, loss of sensation in the lower extremities (peripheral neuropathy), and mental and behavioral changes.[1]
Last updated: 6/15/2011

How is fragile X syndrome inherited?

Fragile X syndrome is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes (the Y chromosome is the other sex chromosome). The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. In women, the FMR1 gene premutation (approximately 55 to 200 repeats) on the X chromosome can expand to more than 200 CGG repeats in cells that develop into eggs that contribute to offspring. This means that women with a premutation (or a full mutation) have an increased risk of having a male or female child with fragile X syndrome. The magnitude of this risk is related to the number of CGG repeats identified.[2] By contrast, the premutation in men does not expand to more than 200 repeats as it is passed to the next generation, and the vast majority of males with a full mutation have fragile X syndrome.[1][2] Men pass the premutation on to all of their daughters and none of their sons.[2] Their sons receive a Y chromosome, which does not include the FMR1 gene.[1] However, there is a risk for fragile X syndrome in a male premutation carrier's grandchildren through his daughters.[2] This is why fragile X syndrome is typically passed on through the mother to her son.
Last updated: 6/15/2011

Is genetic testing available for fragile X syndrome?

Yes, genetic testing is available for fragile X syndrome. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the diagnosis of an FMR1-related disorder (including fragile X syndrome) has been confirmed in a family member.[3] GeneTests lists the names of laboratories that are performing genetic testing for fragile X syndrome. To view the contact information for the clinical laboratories conducting testing, click here. To access the contact information for the research laboratories performing genetic testing, click here. Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, those interested in learning more may need to work with a health care provider or a genetics professional.
Last updated: 6/15/2011

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:
Last updated: 10/18/2013

References