GTR Home > Conditions/Phenotypes > Fragile X tremor/ataxia syndrome

Disease characteristics

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 mutation and is nearly always characterized by moderate intellectual disability in affected males and mild intellectual disability in affected females. Because FMR1 mutations 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.

Associated genes

Clinical features

  • Hypotension
  • Muscle weakness
  • Hyporeflexia
  • Dysmetria
  • Hypertonia
  • Depression
  • Mask-like facies
  • Hypertension
  • Hearing impairment
  • Obsessive-compulsive trait
  • Dysarthria
  • Saccadic smooth pursuit
  • Impaired distal vibration sensation
  • Incoordination
  • Poor fine motor coordination
  • Impotence
  • Anxiety
  • Memory impairment
  • Myalgia
  • Nystagmus
  • Feeding difficulties in infancy
  • Urinary incontinence
  • Hypothyroidism
  • Resting tremor
  • Dementia
  • Disinhibition
  • Cerebellar atrophy
  • Parkinsonism
  • Gait ataxia
  • Bradykinesia
  • Dysdiadochokinesis
  • Intention tremor
  • Cerebral cortical atrophy
  • Postural tremor
  • Abnormality of the autonomic nervous system
  • Action tremor
  • Developmental regression
  • Diffuse cerebral atrophy
  • Bowel incontinence
  • Paresthesia
  • Aplasia/Hypoplasia of the cerebellum
  • Premature ovarian failure
  • Abnormal renal physiology
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Go to complete MedGen record for Fragile X tremor/ataxia syndrome

Clinical resources

Practice guidelines

  • ACMG, 2008
    Clinical significance of tri-nucleotide repeats in Fragile X testing: A clarification of American College of Medical Genetics guidelines
  • 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

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