What Do GP’s Need to Know about Fragile X?

Fragile X is associate with inherited genetic changes in the Fragile X gene. A referral for genetic testing is required for diagnosis. The gene (also known by its scientific name of “FMR1”) can be normal, but it can also exhibit a “premutation” or a “full mutation”. When a premutation or full mutation is present, it can result in a Fragile X condition. These include:

Fragile X syndrome(FXS): An inherited condition affecting intellectual, behavioural, language and social development. It occurs in both males and females who have a full mutation of the FMR1 gene. Early diagnosis and intervention can significantly improve long term outcomes.

Fragile X associated tremor/ataxia syndrome(FXTAS): An adult onset (over 50 years of age) neurological condition, more common and more severe among males, that causes tremor, memory difficulties and balance problems in those with a premutation of the FMR1 gene. (Both males and females who have a premutation are also referred to as “carriers”.) Symptoms that family members may notice (but often attribute to simple aging) include:

  • “Intention” tremors – shaking that occurs during intended/purposeful movement such as reaching for or pouring something, or writing
  • Balance problems (ataxia) that cause falling or instability while walking
  • Numbness in the extremities (neuropathy)
  • Mood instability, irritability, and other changes in personality
  • Short-term memory loss and gradual intellectual decline

Individuals with FXTAS are often misdiagnosed with other conditions including Parkinson’s, Alzheimer’s, dementia, stroke and peripheral neuropathy. If suspected refer to a neurologist.

Fragile X associated primary ovarian insufficiency(FXPOI): A condition affecting ovarian function that can lead to infertility and early menopause. It occurs in some female carriers, who have a premutation of the FMR1 gene.

Who should be referred for genetic testing for Fragile X?

  • Anyone with an intellectual disability (borderline to severe) or autism of unknown cause
  • Anyone with learning difficulties of unknown cause and behavioural features of fragile X (including autistic features, anxiety and ADHD)
  • Anyone with a family history of fragile X who may have inherited the gene
  • Intellectually disabled individuals with a previous fragile X cytogenetic test that was negative or inconclusive
  • Women who experience premature menopause (menopause before the age of 40 years)
  • Adult males (>50 years of age) who present with unexplained ataxia with or without essential tremor, parkinsonism and dementia
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