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Genetics Home Reference: your guide to understanding genetic conditions
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Fragile X syndrome

Reviewed April 2012

What is fragile X syndrome?

Fragile X syndrome is a genetic condition that causes a range of developmental problems including learning disabilities and cognitive impairment. Usually, males are more severely affected by this disorder than females.

Affected individuals usually have delayed development of speech and language by age 2. Most males with fragile X syndrome have mild to moderate intellectual disability, while about one-third of affected females are intellectually disabled. Children with fragile X syndrome may also have anxiety and hyperactive behavior such as fidgeting or impulsive actions. They may have attention deficit disorder (ADD), which includes an impaired ability to maintain attention and difficulty focusing on specific tasks. About one-third of individuals with fragile X syndrome have features of autism spectrum disorders that affect communication and social interaction. Seizures occur in about 15 percent of males and about 5 percent of females with fragile X syndrome.

Most males and about half of females with fragile X syndrome have characteristic physical features that become more apparent with age. These features include a long and narrow face, large ears, a prominent jaw and forehead, unusually flexible fingers, flat feet, and in males, enlarged testicles (macroorchidism) after puberty.

How common is fragile X syndrome?

Fragile X syndrome occurs in approximately 1 in 4,000 males and 1 in 8,000 females.

What genes are related to fragile X syndrome?

Mutations in the FMR1 gene cause fragile X syndrome. The FMR1 gene provides instructions for making a protein called fragile X mental retardation 1 protein, or FMRP. This protein helps regulate the production of other proteins and plays a role in the development of synapses, which are specialized connections between nerve cells. Synapses are critical for relaying nerve impulses.

Nearly all cases of fragile X syndrome are caused by a mutation in which a 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 prevents the gene from producing FMRP. Loss or a shortage (deficiency) of this protein disrupts nervous system functions and leads to the signs and symptoms of fragile X syndrome.

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 FMRP. 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. The premutation is also associated with an increased risk of disorders called fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS).

Related Gene(s)

Changes in this gene are associated with fragile X syndrome.

  • FMR1

How do people inherit fragile X syndrome?

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. X-linked dominant means that in females (who have two X chromosomes), a mutation in one of the two copies of a gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of a gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females.

In women, the FMR1 gene premutation on the X chromosome can expand to more than 200 CGG repeats in cells that develop into eggs. This means that women with the premutation have an increased risk of having a child with fragile X syndrome. By contrast, the premutation in men does not expand to more than 200 repeats as it is passed to the next generation. Men pass the premutation only to their daughters. Their sons receive a Y chromosome, which does not include the FMR1 gene.

Where can I find information about diagnosis or management of fragile X syndrome?

These resources address the diagnosis or management of fragile X syndrome and may include treatment providers.

  • GeneFacts: Fragile X Syndrome: Diagnosis (http://genefacts.org/index.php?option=com_content&view=article&id=496&Itemid=729)
  • GeneFacts: Fragile X Syndrome: Management (http://genefacts.org/index.php?option=com_content&view=article&id=497&Itemid=730)
  • Gene Review: FMR1-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1384)
  • Genetic Testing Registry: Fragile X syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0016667)
  • MedlinePlus Encyclopedia: Fragile X syndrome (http://www.nlm.nih.gov/medlineplus/ency/article/001668.htm)

You might also find information on the diagnosis or management of fragile X syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/fragile-x-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/fragile-x-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about fragile X syndrome?

You may find the following resources about fragile X syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for fragile X syndrome?

  • FRAXA syndrome
  • fra(X) syndrome
  • FXS
  • marker X syndrome
  • Martin-Bell syndrome
  • X-linked mental retardation and macroorchidism

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about fragile X syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding fragile X syndrome?

anxiety ; ataxia ; attention deficit disorder ; autism ; cell ; chromosome ; deficiency ; depression ; disabilities ; disability ; DNA ; gene ; hyperactive behavior ; inheritance ; inherited ; macroorchidism ; marker ; mental retardation ; mutation ; nervous system ; ovarian ; premutation ; protein ; puberty ; sex chromosomes ; spectrum ; syndrome ; testicles ; tremor ; X-linked dominant

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Cornish KM, Turk J, Wilding J, Sudhalter V, Munir F, Kooy F, Hagerman R. Annotation: Deconstructing the attention deficit in fragile X syndrome: a developmental neuropsychological approach. J Child Psychol Psychiatry. 2004 Sep;45(6):1042-53. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15257661?dopt=Abstract)
  • Gene Review: FMR1-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1384)
  • Hagerman PJ, Hagerman RJ. The fragile-X premutation: a maturing perspective. Am J Hum Genet. 2004 May;74(5):805-16. Epub 2004 Mar 29. Review. Erratum in: Am J Hum Genet. 2004 Aug;75(2):352. (http://www.ncbi.nlm.nih.gov/pubmed/15052536?dopt=Abstract)
  • Hagerman RJ. Lessons from fragile X regarding neurobiology, autism, and neurodegeneration. J Dev Behav Pediatr. 2006 Feb;27(1):63-74. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16511373?dopt=Abstract)
  • Jacquemont S, Hagerman RJ, Hagerman PJ, Leehey MA. Fragile-X syndrome and fragile X-associated tremor/ataxia syndrome: two faces of FMR1. Lancet Neurol. 2007 Jan;6(1):45-55. (http://www.ncbi.nlm.nih.gov/pubmed/17166801?dopt=Abstract)
  • Koukoui SD, Chaudhuri A. Neuroanatomical, molecular genetic, and behavioral correlates of fragile X syndrome. Brain Res Rev. 2007 Jan;53(1):27-38. Epub 2006 Jul 17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16844227?dopt=Abstract)
  • Sherman S, Pletcher BA, Driscoll DA. Fragile X syndrome: diagnostic and carrier testing. Genet Med. 2005 Oct;7(8):584-7. (http://www.ncbi.nlm.nih.gov/pubmed/16247297?dopt=Abstract)
  • Sullivan SD, Welt C, Sherman S. FMR1 and the continuum of primary ovarian insufficiency. Semin Reprod Med. 2011 Jul;29(4):299-307. doi: 10.1055/s-0031-1280915. Epub 2011 Oct 3. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21969264?dopt=Abstract)
  • Terracciano A, Chiurazzi P, Neri G. Fragile X syndrome. Am J Med Genet C Semin Med Genet. 2005 Aug 15;137C(1):32-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16010677?dopt=Abstract)
  • Van Esch H. The Fragile X premutation: new insights and clinical consequences. Eur J Med Genet. 2006 Jan-Feb;49(1):1-8. Epub 2005 Dec 5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16473304?dopt=Abstract)
  • Willemsen R, Oostra BA, Bassell GJ, Dictenberg J. The fragile X syndrome: from molecular genetics to neurobiology. Ment Retard Dev Disabil Res Rev. 2004;10(1):60-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14994290?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2012
Published: October 20, 2014