GTR Home > Conditions/Phenotypes > Fragile X syndrome

Summary

Excerpted from the GeneReview: FMR1-Related Disorders
FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related primary ovarian insufficiency (POI). Fragile X syndrome occurs in individuals with an FMR1 full mutation or other loss-of-function variant and is nearly always characterized by moderate intellectual disability in affected males and mild intellectual disability in affected females. Because FMR1 pathogenic variants are complex alterations involving non-classic gene-disrupting alterations (trinucleotide repeat expansion) and abnormal gene methylation, affected individuals occasionally have an atypical presentation with an IQ above 70, the traditional demarcation denoting intellectual disability (previously referred to as mental retardation). Males with an FMR1 full mutation accompanied by aberrant methylation may have a characteristic appearance (large head, long face, prominent forehead and chin, protruding ears), connective tissue findings (joint laxity), and large testes after puberty. Behavioral abnormalities, sometimes including autism spectrum disorder, are common. FXTAS occurs in males (and some females) who have an FMR1 premutation and is characterized by late-onset, progressive cerebellar ataxia and intention tremor. FMR1-related POI (age at cessation of menses <40 years) occurs in approximately 20% of females who have an FMR1 premutation.

Genes See tests for all associated and related genes

  • Also known as: FMRP, FRAXA, POF, POF1, FMR1
    Summary: fragile X mental retardation 1

Clinical features

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Practice guidelines

  • 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.
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    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
  • 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
  • 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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