Fragile X-Associated Tremor/Ataxia Syndrome, or FXTAS (pronounced fax-tass) is a disorder which affects older men who are carriers of a small "premutation" in the same gene that causes fragile X syndrome, the most common cause of inherited mental retardation. Nearly 1 in 800 men in the general population carries this mutation in the fragile X gene, and research suggests that as many as 30 percent of carriers -- roughly 1 in 3,000 men -- may develop FXTAS later in life.
FXTAS is a progressive neurodegenerative disorder that predominantly affects men over age 50 and results in tremors, balance problems and dementia that become increasingly more severe with age. It is easily identified with a standard DNA blood test or by looking for a family history of fragile X in grandchildren. While only 17 percent of the fragile X carrier men in their 50s had FXTAS, the percentage of individuals with tremors and balance problems increased with each decade of life, to 38 percent of men in their 60s, 47 percent of men in their 70s, and 75 percent of men in their 80s. Initial signs of the disorder may include difficulty writing, using eating utensils, pouring water and walking. These initial symptoms progress over years or even decades, until carrying out many of the tasks of daily living and walking without assistance becomes difficult or impossible. Other features include short-term memory loss, anxiety, decreased sensation in the lower extremities to touch and vibration, lower-limb muscle weakness and parkinsonism.
The fragile X mental retardation 1 gene, or FMR1, under normal conditions produces a protein that maintains the proper functioning of nerve cells in the brain. The gene causes both fragile X syndrome and FXTAS when a particular segment of DNA is repeated too many times. The repetition informally is called a "CGG repeat" because it contains the same trio of DNA building blocks -- cytosine, guanine, and guanine in the same repetitive order.
The average person has 30 CGG repeats in the FMR1 gene. When an individual has 200 or more CGG repeats in the FMR1 gene, the individual makes little or no FMR1 protein and has fragile X syndrome. With 55 to 200 CGG repeats, an individual is considered a carrier of the premutation, which can lead to FXTAS later in life and to fragile X (the full mutation) in the next generations. Male carriers are at high risk to develop FXTAS, as well as for passing on the gene mutation to all of their daughters, who in turn are at risk to have children with fragile X syndrome.
In the brain, there are accumulations of abnormal cellular material in the form of inclusion bodies in the nuclei of brain cells, (specifically neurons and astrocytes) throughout the cortex and brainstem regions. The greatest densities were found in the hippocampus and frontal cortical regions, areas of the brain that control movement and are important in learning, memory and emotion.
No treatment is currently available although family genetic counseling may help later generations. UC Davis M.I.N.D Institute. JAMA 1/28/04