For the Genetic Counselor

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 (see “Testing & Diagnosis ”).
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. Therefore, daughters and 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 daughters of the male patient with FXTAS will have inherited the premutation and are at risk to have children with fragile X syndrome. These daughters are also at increased risk to have ovarian dysfunction and fertility problems related to primary ovarian insufficiency. 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. 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. The following articles will be helpful to both professionals and families impacted by FXTAS:

• The Impact of FXTAS on Patients and Their Spouses
• Fragile X-Associated Tremor/Ataxia Syndrome: Clinical Features, Genetics, and Testing Guidelines
• Genetic Counseling for Fragile X Syndrome: Updated Recommendations of the National Society of Genetic Counselors
• Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): An Introduction for Families and Providers (brochure)
  
• Recommendations from Multi-disciplinary Focus Groups on Cascade Testing and Genetic Counseling for Fragile X-associated Disorders

Contributed by: Liane Abrams, MS, CGC