Fragile X-associated tremor/ataxia syndrome difficult to diagnose

Fragile X-associated tremor/ataxia syndrome can be difficult to diagnose and should have guidelines for diagnostic testing, according to a study in the July 26 issue of Neurology, the scientific journal of the American Academy of Neurology. A second study found chemotherapy aggravated symptoms in one woman's case.

Fragile X syndrome is the most common inherited cause of mental retardation. Fragile X-associated tremor/ataxia syndrome (FXTAS) was recently defined as a disorder that affects carriers of the Fragile X gene, called FMR1. People with FXTAS carry the FMR1 gene and develop symptoms later in life, usually starting in their 60s and 70s. Ataxia is the inability to coordinate voluntary muscle movements. Predominantly occurring in males, FXTAS could affect as many as one in 3,000 men over age 50. Male carriers pass the gene to all daughters but none of their sons. Female carriers have a 50 percent chance of passing the gene to each child.

A multi-center study found 56 people had received 98 prior diagnoses, including parkinsonism and essential tremor, before FXTAS was concluded. The researchers believe this was partly due to the recent definition of FXTAS and a lack of familiarity with the disorder. The information about previous diagnoses encouraged them to develop guidelines for diagnostic testing for FXTAS.

"Men age 50 and older who develop unexplained ataxia should undergo testing to check if they have the FMR1 gene," said co-author Maureen A. Leehey, MD, of the University of Colorado Health Sciences Center in Denver. "Also men 50 and older who have tremor, parkinsonism, or dementia, along with a family history of developmental delay, autism, mental retardation, or premature ovarian failure, should be tested for the gene."

These guidelines are reasonable but may change in the future as larger numbers of patients are detected, according to an editorial published in the same issue of Neurology.

"A family history of mental retardation or tremor/ataxia syndromes should be sought in such patients," said editorial author Thomas Gasser, MD, of the Hertie-Institute for Clinical Brain Research at University of Tuebingen in Germany.

A second study in Ireland examined a 70-year-old woman with mild ataxia and tremor that became severe after receiving chemotherapy to treat breast cancer. She had two sons with Fragile X syndrome. The researchers concluded she had FXTAS after a genetic test using DNA from a blood sample showed that she carried the FMR1 gene. Her symptoms became mild again after chemotherapy stopped.

"About 1 in 259 women carry the FMR1 gene, but FXTAS is rarely reported in women," said co-author John P. O'Dwyer, MRCPI, of St. Vincent's University Hospital in Dublin. "You might expect to see FXTAS more often, but it may only become evident when toxic effects from a procedure like chemotherapy push mild symptoms to the forefront."

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