Genetic brain disorder 'commonly misdiagnosed'

A newly-discovered genetic disorder that causes tremors, balance problems and memory loss in men over fifty could be much more widespread that first thought, according to a new US study. Many people affected by the condition are currently being misdiagnosed with either senile dementia, Parkinson's or Alzheimer's disease, say the researchers, who are based at the University of California Davis Medical Center in Sacramento. They estimate that fragile X-associated tremor/Ataxia syndrome (FXTAS) could affect as many as one in 3000 men in later life. Team leader Paul Hagerman hopes that the findings, published in the Journal of the American Medical Association, will lead to routine genetic testing of people with atypical Parkinson's disease.

FXTAS is caused by a small alteration in a gene called FMR-1, which is also involved in fragile X syndrome, the most common cause of inherited mental retardation in children. In FXTAS, the FMR-1 alteration takes the form of a short section of repeated genetic code called a 'premutation'. Children with fragile X have an expanded version of this alteration, called a 'full mutation'. It is thought that around one in 259 women and one in 813 men carry FMR-1 premutations: fragile X occurs when a premutation expands into a full mutation, as it is passed from a carrier mother to her child.

Paediatrician Randi Hagerman began looking for a connection between fragile X children and their relatives after several of the patient's mothers expressed concern about their fathers' balance and memory problems. Along with her husband Paul and other colleagues, she studied 192 people who had family members with fragile X syndrome, and found that many of the men who carried a FMR-1 premutation had symptoms of FXTAS. Women are not usually affected by FXTAS, since the FMR-1 gene is located on the X-chromosome. Women, unlike men, inherit two different X-chromosomes so a normal gene on one can often compensate for the effects of a faulty gene on the other.

The researchers found that in men with a premutation, the risk of FXTAS increased with age, affecting 17 percent of men in their fifties and 75 per cent of those in their eighties. 'FXTAS may be one of the most common causes of tremor and balance problems in the adult population, yet it is being misdiagnosed because neurologists who see adults with movement disorders are not aware that they need to look for a family history of fragile X in grandchildren or to check for the presence of the premutation in the fragile X gene' said Randi Hagerman.

It is not yet known how the prognosis for people with FXTAS differs compared to those affected by Parkinson's disease, says team member Elizabeth Berry-Kravis. But a correct diagnosis might prevent the prescription of inappropriate medicines, or even brain surgery. Further research into FXTAS and the genetic mutation that causes it could also lead to new drug treatments, say the researchers.