Researchers to identify key brain, behavioral changes in aging women with premutations of the Fragile X gene

LAWRENCE — Only in the past 20 years have scientists recognized a condition known as Fragile X-associated tremor/ataxia syndrome (FXTAS). First documented in a small group of men who had grandchildren with Fragile X syndrome, it has more recently been identified in women. Researchers at the University of Kansas Life Span Institute now are working to learn more about its effects in women.

At one time, the genetic markers, or premutation alleles, of the Fragile X gene FMR1 were thought to be relatively benign in an individual carrying them in their genetic code; researchers only knew that the premutation alleles contributed to the risk for having a child with Fragile X syndrome, which causes a range of developmental problems in young children. Scientists now know that premutation alleles can contribute to severe changes in cognition and movement as carriers age. Those changes include tremor, balance issues and memory loss, and it can lead to a loss of independence.

“We know very little about which premutation carriers will develop FXTAS,” said Matt Mosconi, associate director and senior scientist at KU’s Life Span Institute and professor of clinical child psychology. “We know males are at greater risk than females. Otherwise, we don’t know a whole lot about which premutation carriers are going to get it. And we don’t know what changes are happening in the brain, as those seem to be different in men and women.”

Mosconi’s team, in collaboration with colleagues at Kansas State University and the University of California-Davis, are leading new studies of motor, cognitive and brain changes in female FMR1 premutation carriers to identify key symptoms to track during aging. They hope to better understand the causes of FXTAS in females.

Approximately 1 in 450 men carries the premutation that can lead to FXTAS, compared to about 1 in 200 women. Of those, about 40% of men and 16-20% of women will develop FXTAS symptoms. While usually more severe in men, FXTAS can still be debilitating in women.  

FXTAS symptoms typically present when individuals reach their 50s or 60s but often are missed during early stages or misdiagnosed as Parkinson's or Alzheimer's disease. Greater knowledge of the key brain and behavioral changes associated with FXTAS in women is essential for identifying initial disease stages when treatments may be most effective.

Mosconi’s team is currently recruiting women ages 60-75 with known FMR1 premutations and those without to participate in tests examining changes in cognition, grip strength and posture, and brain function in aging.

The long-term goal of this study is to clarify neurodegenerative mechanisms of FXTAS in women so that more sensitive methods can be established to track disease progression and development, as well as to advance targeted therapeutic interventions.

For more information about participating in FMR1 research, visit the KU FMR1 research website or contact the KU BRAIN Lab at BRAINlab@ku.edu.

Photo illustration: Fragile X-associated tremor/ataxia syndrome is a genetic disorder first documented in a small group of men who had grandchildren with Fragile X syndrome. Scientists are now looking to learn more about its effect in women.