Fragile X syndrome
What is fragile X syndrome?
Fragile X syndrome is a genetic condition that runs in families. It is the most common known genetic cause of intellectual disability and the most common known single-gene cause of autism. Fragile X syndrome is caused by a problem (mutation) in the FMR1 (fragile X mental retardation 1) gene; this problem is present in every cell of a person's body (skin cells, blood cells, etc.). When there is a mutation in the FMR1 gene, a person’s body makes very little or none of the fragile X mental retardation protein (FMRP). The FMRP protein helps create other proteins the body needs and helps develop the synapses, which are the connections between our nerve cells. The lack of this protein affects a person’s development and causes intellectual disability (formerly known as mental retardation), developmental delay, and various physical characteristics. It can affect both males and females, though it generally affects males more severely.
Fragile X syndrome is part of a group known as the FMR1-related disorders. In addition to fragile X syndrome, this group includes fragile X-associated tremor/ataxia syndrome (FXTAS) and FMR1-related primary ovarian insufficiency (FXPOI). All the FMR1-related disorders can affect both men and women, with the exception of FXPOI (women only). All the FMR1-related disorders are passed from one generation to the next through mutation of the FMR1 gene, which is on the X chromosome. The most common cause of these FMR1-related disorders is having too many CGG repeats in the FMR1 gene. Every gene is made up of a string of nucleotide bases in a specific order; the nucleotide bases are A, T, G, and C. The length of each gene and the specific code are different, and sometimes specific parts of the code are repeated. For the FMR1 gene, having up to 44 CGG trinucleotide ("tri" meaning "three", "nucleotide" meaning "nucleotide base") repeats is typical. A person who has between 45 and 54 CGG repeats is considered "gray zone" or "borderline", meaning the potential exists for that repeat to become larger and then be considered a premutation. These individuals do not show any signs of any of the FMR1-related disorders. When a person has between 55 and 200 CGG repeats, they have the premutation and can have either FXTAS and/or FXPOI. If a person has over 200 CGG repeats in their FMR1 gene and it becomes methylated (meaning "turned off"), they have fragile X syndrome, meaning they have the full mutation and will have signs of the disorder. The number of CGG repeats in the FMR1 gene can be determined through molecular testing of the FMR1 gene.
While there is no cure for fragile X syndrome, FXTAS, or FXPOI, there are treatments and strategies to help individuals with FMR1-related disorders and their families. For fragile X syndrome, this can include special education, medicines to help address issues with behavior, and routine treatment of medical problems. Individuals with FXTAS require supportive care for both motor and mental issues. Women with FXPOI should meet with a reproductive endocrinologist, which is a doctor who specializes in hormone-related issues with reproduction/pregnancy. Individuals seeking additional information and support relating to fragile X syndrome should visit the website for the National Fragile X Foundation at https://fragilex.org/.
- Fragile X syndrome. McLennan Y, Polussa J, Tassone F, Hagerman R. . 2011 May;12(3):216-24. doi: 10.2174/138920211795677886.
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Are there other names for fragile X syndrome?
Fragile X syndrome is also known by the following names:
- X-linked mental retardation and macroorchidism
- Martin-Bell syndrome
- fragile X mental retardation
- FRAXA syndrome
- fra(X) syndrome
- marker X syndrome
- Escalante's syndrome
There are multiple names for fragile X syndrome, so it is important to make sure families and doctors are on the same page and using the same name. If a doctor is using an unfamiliar term, ask them if they are using a different name for fragile X syndrome. Another reliable source for alternative names for fragile X syndrome is the Genetics Home Reference website, which can be found at Genetics Home Reference Fragile X Synonyms.
How common is fragile X syndrome?
Testing of the FMR1 gene has helped estimate how common fragile X syndrome is in the population. Studies have shown that approximately 16 to 25 males in every 100,000 males has fragile X syndrome. Researchers believe the number of females with fragile X syndrome is half the number of males who are affected (approximately 8 to 12 females in every 100,000 females). For another way to look at these numbers, studies have shown that approximately 1 in 3600 males and 1 in 4000 to 6000 females has fragile X syndrome (the full mutations, greater than 200 CGG repeats).
More information and support for those with fragile X syndrome and their families can be found by visiting the National Fragile X Foundation.
What is the usual abbreviation for fragile X syndrome?
Fragile X syndrome is most often abbreviated as FXS.