GRAPEVINE, TEX. — Men who carry the fragile X syndrome gene may be at risk for progressive tremors and weakness as they age, said James Grigsby, Ph.D., at a meeting sponsored by the American College of Medical Genetics.
An estimated 750,000 men carry the gene for fragile X syndrome.“Formerly, these individuals were thought to be unaffected,” said Dr. Grigsby, director of the division of Health Care Policy and Research at the University of Colorado Health Sciences Center. “Men in later life are far more affected than women.”
Epidemiologic studies now show that a high percentage of males develop fragile X-associated tremor-ataxia syndrome (FXTAS). The incidence in men now is thought to be between 1 in 250 to 1 in 813; in women the incidence is 1 in 250–259.
But clinical studies of men and women with the carrier status are revealing more about the neurologic signs and symptoms and are discovering distinct findings on the brains of carriers through MRI.
In one study of 40 men, more than half were affected after age 80; however, 7 (18%) had symptoms occur at age 50–59, Dr. Grigsby said. Syndrome characteristics in a study of 26 affected men included gait ataxia in 25 (96%), intention tremor in 18 (69%), lower extremity weakness in 14 (54%), lower extremity neuropathy in 16 (62%), bradykinesia in 15 (58%), rigidity in 9 (35%), dysarthria in 20 (77%), dysmetria in 24 (92%), bowel incontinence in 8 (31%) and bladder incontinence in 14 (54%), impotence in 21 (81%), cognitive deficit in 19 (73%), and heart failure in more than half.
“The clinical signs are similar to Parkinson's disease,” Dr. Grigsby said. “In studying the cognitive aspect, we don't observe a high level of dementia, and the verbal IQ isn't affected. But there is impairment in working memory, speed and capacity of information processing, and executive cognitive functions.”
Additionally, physicians are finding a high level of heart failure and hypertension in men with FXTAS, he said.
One study of 25 men showed the mean age of onset of FXTAS was 62 years. Many of the men had completed college, with a mean of 16 years of education, and they had a mean IQ of 102.
“Although there was a high number of college graduates in the group, the cognitive levels were less than expected of college graduates,” he said.
Over time the men showed increased apathy, lowered verbal fluency, higher level of disinterest, inappropriate speech, irritability, and an inability to stick to the task at hand, as assessed by a number of tests, including the letter-number sequencing and digit span subtests of the Wechsler Adult Intelligence Scale, Version III.
“There also was a 50% decrease in short-term memory,” according to Dr. Grigsby, reporting on unpublished data
On MRI, there are white-matter lesions and atrophy of the cortex, brainstem, and cerebellum but no evidence of inflammation, Dr. Grigsby said.