Professional Resources for FXTAS


Physicians practicing in a number of disciplines may encounter patients who are potentially at risk for or have been diagnosed with FXTAS. Given the multi-system nature of this condition, a patient may be under the care of multiple or varying specialists. These include but are not limited to:

  • Neurologists (for tremor, ataxia, memory loss)
  • Psychiatrists (for personality change, depression, mood disorders)
  • Psychologists (for cognitive impairment)
  • Movement disorders specialists (for tremor, ataxia)
  • Medical geneticists (for any of the above, positive family history)
  • Internists, Urologists (for hypertension or impotence)
  • Orthopedists (for neuropathy, gait abnormalities)
  • Physiatrists (for rehabilitation)

Since FXTAS shares many symptoms with other conditions, patients with FXTAS are often misdiagnosed with Parkinson’s disease, Alzheimer’s, psychiatric disorders, dementia, stroke, other ataxias, and peripheral neuropathy.

If a patient has any of the symptoms of FXTAS, it is imperative to establish their FMR1 status. This is done by ordering the FMR1 DNA test. There is a systematic diagnostic protocol for FXTAS developed by specialists around the globe.

In order to utilize this diagnostic criteria, the patient should have:

  • FMR1 testing
  • Brain MRI imaging
  • A neurological evaluation.

Because patients with FXTAS may have family members with either Fragile X syndrome (FXS) or Fragile X-associated primary ovarian insufficiency (FXPOI), physicians should take a family history and inquire about the following:

  • Adult onset neurological symptoms described in FXTAS in other adult family members.
  • Female relatives with infertility or early menopause.
  • Male and female relatives with intellectual disability, autism, developmental, behavioral, language or learning disorders.

Next Steps

  • If you are a physician whose primary patient population does not include those with movement disorders or neurological problems (such as a urologist, internist, orthopedist, etc.), any patient with symptoms similar to FXTAS should be referred to a neurologist or movement disorders specialist.
  • If FXTAS is confirmed in your patient, genetic counseling by a board-certified genetic counselor is highly recommended. The children, grandchildren and other relatives of the patient may be at risk for other Fragile X conditions and positive carrier status. Additionally, there are often female relatives who unknowingly may have Fragile X-associated primary ovarian insufficiency (FXPOI) and are undergoing expensive and extensive fertility treatments not knowing they are at risk to have a child with Fragile X syndrome (FXS).
  • Most metropolitan and many community medical centers employ genetic counselors. If there is not one in your referral network you can find one through the National Society of Genetic Counselors.
  • There are clinics around the country dedicated to serving those with one of the Fragile X. Patients can be referred to the clinic nearest them. Visit our Fragile X Clinics to find a clinic nearest your patient and/or their family.

Additional Medical Information

For more medical information and important articles pertaining to FXTAS click here.

  • FXTAS – Clinical Features, Genetics & Testing Guidelines
    An in-depth professional article covering all aspects of FXTAS. A great resource for doctors and professionals, but also provides great insight for family members.
    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder with core features of action tremor and cerebellar gait ataxia. Frequent associated findings include parkinsonism, executive function deficits and dementia, neuropathy, and dysautonomia. Magnetic Resonance Imaging studies in FXTAS demonstrate increased T2 signal intensity in the middle cerebellar peduncles (MCP sign) in the majority of patients. Similar signal alterations are seen in deep and subependymal cerebral white matter, as is general cortical and subcortical atrophy. The major neuropathological feature of FXTAS is the presence of intranuclear, neuronal, and astrocytic, inclusions in broad distribution throughout the brain and brainstem. FXTAS is caused by moderate expansions (55–200 repeats; premutation range) of a CGG trinucleotide in the Fragile X mental retardation 1 (FMR1) gene, the same gene which causes Fragile X syndrome when in the full mutation range (200 or greater CGG repeats). The pathogenic mechanism is related to overexpression and toxicity of the FMR1 mRNA per se. Although only recently discovered, and hence currently under-diagnosed, FXTAS is likely to be one of the most common single-gene disorders leading to neurodegeneration in males. In this report, we review information available on the clinical, radiological, and pathological features, and prevalence and management of FXTAS. We also provide guidelines for the practitioner to assist with identifying appropriate patients for DNA testing for FXTAS, as well as recommendations for genetic counseling once a diagnosis of FXTAS is made. © 2007 Movement Disorder Society
    Key words: Fragile X-associated tremor/ataxia syndrome; tremor; ataxia; FMR1; Fragile X syndrome
  • Fragile X-associated Tremor-Ataxia Syndrome Consensus Documents on Clinical Practices
    Fragile X-associated Tremor-Ataxia Syndrome (2012-Oct)
    Guidelines for best practices generated by consensus of all the physicians working on Fragile X. A great resource for doctors and professionals, but also provides great insight for family members.

Genetic Counselors

Though many genetic counselors are familiar with Fragile X syndrome, it is less common for those outside the neurology setting to be familiar with Fragile X-associated tremor/ataxia syndrome (FXTAS).

If you suspect adult patients may have FXTAS, it is first and foremost essential that you confirm they are FMR1 premutation carriers by conducting molecular testing.

In the evaluation/counseling of patients with confirmed or suspected FXTAS, a detailed three-generation pedigree should include inquiries regarding:

  • Adult onset neurological symptoms described in FXTAS (see “What is FXTAS ”) in patient and other adult family members,
  • Female relatives with infertility, early menopause,
  • Male and female relatives with intellectual disability, autism, developmental, behavioral, language or learning disorders.

If a patient is diagnosed with FXTAS the following issues should be addressed:

  • In a male patient:
    • The patient’s mother is an obligate carrier.
    • All daughters of the male patient with FXTAS will have inherited the premutation and are at risk to have children with Fragile X syndrome (FXS). These daughters are also at increased risk to have ovarian dysfunction and fertility problems related to primary ovarian insufficiency (FXPOI). A female family member could be undergoing (often expensive and invasive) fertility treatments while unaware that she may be a carrier of the premutation and at risk of having an affected child.
    • Relatives of the patient and relatives of his mother, including children, grandchildren, nieces, nephews and cousins, are at risk for FXTAS, Fragile X syndrome, learning disabilities, mental health issues, or to be carriers of the FMR1 premutation.
    • Siblings of the patient are at risk to present with FXTAS. Therefore, ataxia, psychiatric and neurological problems need to be identified.
    • All grandchildren through daughters of the male patient with FXTAS are at a 50 percent risk to inherit the FMR1 pre- or full mutation.
  • All children of both genders of the female patient with FXTAS are at a 50 percent risk to inherit the FMR1 pre- or full mutation.

When providing genetic counseling services to a family with a newly diagnosed member with FXTAS, cascade testing for individuals at risk to be premutation carriers or affected with a full mutation should take place within the genetic counseling services, or a referral should be made to counseling/testing services local to the at-risk family members.

It is important to keep in mind the cognitive and psychiatric issues common in individuals with FXTAS when reviewing the genetic and familial implications of this diagnosis.

  • Many patients may experience confusion and emotional reactions to learning the genetic nature of their condition as well as the implications for their children and other relatives.
  • It is important to involve the caregiver in these sessions, along with other family members who can absorb and communicate important genetic information.