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Summary

Excerpted from the GeneReview: FMR1 Disorders
FMR1 disorders include fragile X syndrome (FXS), fragile X-associated tremor/ataxia syndrome (FXTAS), and fragile X-associated primary ovarian insufficiency (FXPOI). Fragile X syndrome occurs in individuals with an FMR1 full mutation or other loss-of-function variant and is nearly always characterized in affected males by developmental delay and intellectual disability along with a variety of behavioral issues. Autism spectrum disorder is present in 50%-70% of individuals with FXS. Affected males may have characteristic craniofacial features (which become more obvious with age) and medical problems including hypotonia, gastroesophageal reflux, strabismus, seizures, sleep disorders, joint laxity, pes planus, scoliosis, and recurrent otitis media. Adults may have mitral valve prolapse or aortic root dilatation. The physical and behavioral features seen in males with FXS have been reported in females heterozygous for the FMR1 full mutation, but with lower frequency and milder involvement. FXTAS occurs in individuals who have an FMR1 premutation and is characterized by late-onset, progressive cerebellar ataxia and intention tremor followed by cognitive impairment. Psychiatric disorders are common. Age of onset is typically between 60 and 65 years and is more common among males who are hemizygous for the premutation (40%) than among females who are heterozygous for the premutation (16%-20%). FXPOI, defined as hypergonadotropic hypogonadism before age 40 years, has been observed in 20% of women who carry a premutation allele compared to 1% in the general population.

Genes See tests for all associated and related genes

  • Also known as: FMRP, FRAXA, POF, POF1, FMR1
    Summary: fragile X messenger ribonucleoprotein 1

Clinical features

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Practice guidelines

  • ACMG, 2021
    Laboratory testing for fragile X, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)
  • EMQN, 2015
    EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders.
  • ACMG, 2013
    ACMG Standards and Guidelines for fragile X testing: a revision to the disease-specific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics and Genomics.
  • ACMG, 2013
    Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions.
  • NSGC, 2012
    Genetic counseling and testing for FMR1 gene mutations: practice guidelines of the national society of genetic counselors.
  • ACMG, 2008
    Clinical significance of tri-nucleotide repeats in Fragile X testing: A clarification of American College of Medical Genetics guidelines
  • ACMG, 2008
    Clinical genetics evaluation in identifying the etiology of autism spectrum disorders (See 2013 Update)
  • ACMG, 2005
    Fragile X syndrome: Diagnostic and carrier testing
  • ACMG, 2001
    Technical Standards and Guidelines for Fragile X: The First of a Series of Disease-Specific Supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics (See 2021 Update)
  • EuroGenetest, 2011
    Clinical utility gene card for: fragile X mental retardation syndrome, fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency.

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