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

The Impact of the COVID-19 Pandemic on School-Aged Children with Fragile X Syndrome

The pandemic caused by the spread of the coronavirus disease (COVID-19), beginning in early 2020, had an impact beyond anything experienced in recent history. It is important to understand how this pandemic era has impacted school-aged children with FXS so that we may continue to successfully navigate the changes that come with living through a pandemic and to understand what we can improve in the case of a future pandemic.