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Fragile X–associated
tremor/ataxia syndrome is a genetic disorder that affects mostly
men and causes tremor, loss of coordination, and dementia.
Fragile X–associated tremor/ataxia syndrome, a newly recognized disorder, may affect as many as 1 of 3,000 men over 50.
Fragile X-associated tremor/ataxia syndrome results from a less extensive abnormality (called a premutation) in a gene on the X chromosome (men have an X and a Y chromosome, and women have 2 X chromosomes). A more extensive (full) mutation in this gene causes fragile X syndrome (which causes mental retardation) in children. People with the premutation are considered carriers. Men with the premutation pass it to their daughters (but not to their sons). Most women with the premutation are unaffected and thus may unknowingly pass the gene on to their sons (grandsons of affected men). Children of such a woman have a 50% chance of inheriting the premutation. When the premutation is passed from mother to child, it sometimes changes into a full mutation, causing fragile X syndrome in the child.
About 30% of men with the premutation and fewer than 5% of women with the premutation develop fragile X–associated tremor/ataxia syndrome as adults. The risk of developing the disorder increases as people age.
Symptoms
Symptoms usually develop later in life. The first symptom is often tremors in the hands, typically when people try to do a task. Other symptoms include loss of coordination, slow movements, stiffness, and decreased facial expression.
People may have problems remembering recent events and solving problems. They may think more slowly. These problems often progress to dementia. People may also have personality changes. They may become depressed, anxious, impatient, hostile, and moody.
Sensation in the feet may be lost. Internal organs may malfunction. Affected people may feel light-headed when they stand because blood pressure does not increase as it normally does (called orthostatic hypotension). They may have to urinate more frequently. Eventually, they may lose control of the bladder and bowel movements.
After symptoms appear, people may live from about 5 to 25 years.
In women with the premutation, symptoms are usually less severe, possibly because they have another X chromosome, which seems to protect against the effects of the X chromosome with the premutation. Also, women with the premutation are more likely to have early menopause, infertility, and ovarian dysfunction than women without it.
Diagnosis and
Treatment
Because this disorder is newly recognized, the diagnosis is sometimes missed or mistaken for disorders that cause similar symptoms, such as Parkinson's disease or Alzheimer's disease.
Genetic testing can confirm the diagnosis. Magnetic resonance imaging (MRI) may be done to check for characteristic abnormalities in the brain.
Grandfathers of children with fragile X syndrome should be asked whether they have symptoms suggesting fragile X–associated tremor/ataxia syndrome. Daughters and grandsons of affected men should have genetic counseling. They can be tested for the premutation so that they can make decisions about whether or not to have children and whether or not to have prenatal testing if pregnancy occurs.
Tremors can often be relieved by many of the drugs used to control tremors due to Parkinson's disease (see Movement Disorders: Drugs Used to Treat Parkinson's Disease ).
Last full review/revision August 2007 by David Eidelberg, MD; Michael Pourfar, MD
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