Authors: Michelle H. S. Tosin, Glenn T. Stebbins, Christopher G. Goetz, Randi J. Hagerman, David Hessl, Melissa A. Zolecki, Peter K. Todd, Maureen A. Leehey and Deborah A. Hall


Fragile X-associated tremor/ataxia syndrome (FXTAS) is a genetic disorder that has motor and non-motor components. In 2006, the first version of the FXTAS Rating Scale (FXTAS-RS) was created to measure a person’s severity of FXTAS. However, this scale was created by selecting items from already-validated scales for other movement disorders, like Parkinson’s disease. This proved to be problematic as these items were not modified to meet FXTAS-specifics. In fact, one study that analyzed 295 videotapes of patients with FXTAS found that the items on the original FXTAS-RS were inadequate, or at the very least, needed to be revised.

Researchers took those findings and set out to develop a revised version of the FXTAS-RS. Their aim was to develop and collect patients’ input on a revised version of the FXTAS-RS designed to specifically assess FXTAS motor signs. Once developed, researchers would then provide initial validation of the revised FXTAS-RS for motor signs.

To do this, researchers conducted a two-phase, mixed-method approach to revise and validate the FXTAS-RS. In Phase 1, a panel of nine specialists across the United States revised the 2006 version of the FXTAS-RS through five rounds of expert panel discussions. In Phase 2, the updated FXTAS-RS content was validated through cognitive pretesting with 10 patient-provider pairs. During Phase 2, patients with FXTAS and their providers assessed the FXTAS-RS for clarity, comprehensiveness, and relevance of items to FXTAS motor signs. Major and minor revisions were then incorporated into the revised version of the scale until researchers found that there were no other items that required adjustments to the scale.

After successfully completing Phase 1 and Phase 2, the revised version of the FXTAS-RS was established with 18 items covering five domains and 13 subdomains of motor signs, all specific to FXTAS. The revised scale has been successfully validated for content and it is now ready for large-scale field validation.

Why This Matters

Currently, there are no treatments available for FXTAS or its related symptoms, and up until now, most FXTAS research has been observational in nature. However, thanks to an active group of Fragile X researchers, the FXTAS field has recently advanced to early clinical trials, with the shift in focus moving towards treatment. With this shift underway, researchers need an accurate, standardized tool to measure FXTAS. After large-scale field validation, the new and improved FXTAS-RS will be used as a main outcome measure for FXTAS studies and trials of the future.

Next Steps

Now that the first version of the FXTAS-RS has been successfully revised and validated for content, it is now ready for large-scale field validation! Future research will focus on the clinical validation of the revised version of the FXTAS-RS, with a goal launch of this year, 2023. Further down the line, the FXTAS-RS tool will be translated to be utilized globally.

Funding: This study was funded by the Zivin Family Foundation, Steve, and Shirley Kaufman.

more research results

FMR1 Carriers Report Executive Function Changes Prior to Fragile X-Associated Tremor/Ataxia Syndrome: A Longitudinal Study

Authors:  David Hessl, PhD, Karina Mandujano Rojas, BS, Emilio Ferrer, PhD, Glenda Espinal, BS, Jessica Famula, MS, Andrea Schneider, PhD, Randi Hagerman, MD, Flora Tassone, PhD, and Susan M. Rivera, PhD Summary: People with Fragile X-associated tremor/ataxia syndrome (FXTAS) are not only affected by movement problems, but also by changes in cognition, especially what is referred to as “executive dysfunction” (problems with memory, disinhibition, attention, planning). Moreover, male individuals living with the premutation have [...]

Healthcare Experiences of African American Women with a Fragile X Premutation

Authors: Andy King, Nadia Ali, Cecelia Bellcross, Fabienne Ehivet, Heather Hipp, Jessica Vaughn, Emily G. Allen An estimated 1 in 291 women carry a Fragile X premutation (PM) and there is little evidence that this number differs by racial and ethnic background. Yet African American women who have a PM continue to be underrepresented in Fragile X research. African Americans experience disparities in access, quality, and outcomes of their healthcare, including reproductive and women’s [...]

Emotion Dysregulation in Fragile X Syndrome

By Mya Jones Authors:  Rebecca C Shaffer, Debra L Reisinger, Lauren M Schmitt, Martine Lamy, Kelli C Dominick, Elizabeth G Smith, Marika C Coffman, Anna J Esbensen Summary: A large portion of individuals with Fragile X Syndrome (FXS) experience the inability to change how strongly they feel an emotional experience or how they respond to the experience, referred to as emotion dysregulation. Cincinnati Children’s Fragile X Center team reviewed the surrounding and relevant research conducted [...]