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
Summary
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
Benefit of BPN14770 for Cognition and Daily Function in Fragile X Syndrome
Your summary of the results, including why it matters to you and next steps, from the Dr. Liz Berry-Kravis and Tetra Therapeutics BPN14770 trial results published in Nature Medicine. This was a randomized, double-blind, placebo-controlled, two-period crossover study.
Cortical Gyrification and Its Relationships With Molecular Measures and Cognition in Children With the FMR1 Premutation
Jun Yi Wang and the study team out of the UC Davis MIND Institute are interested in learning more about the premutation carrier condition in relations to brain development and its impact on cognition. These mental processes impact the higher-level functions of the brain including language, learning new things, and making decisions.
Telehealth-Enabled Behavioral Treatment for Problem Behaviors in Boys With Fragile X Syndrome: A Randomized Controlled Trial
Dr. Hall and his team at Stanford University are learning about potential behavioral treatments for problem behaviors. Previous research suggests that problem behaviors, like aggression, self-injury, and property destruction, may occur at higher rates in individuals with FXS.
A Genotype-Phenotype Study of High-Resolution FMR1 Nucleic Acid and Protein Analyses in Fragile X Patients with Neurobehavioral Assessments
We know that FMRP is expressed throughout our body, including our blood, tissues, and brain. Levels of FMRP in the blood of patients with FXS have been positively correlated with cognitive performance, specifically intelligence quotient and adaptive behavior.
Clustering of Comorbid Conditions Among Women Who Carry an FMR1 Premutation
RESEARCH RESULTS ROUNDUP — The authors sought to clarify how often other health-related conditions, such as migraines and sleep problems, occur among women with a premutation.
Cerebellar-Cortical Function and Connectivity during Sensorimotor Behavior in Aging FMR1 Gene Premutation Carriers
RESEARCH RESULTS ROUNDUP — Investigation into how aging as a premutation carrier of the FMR1 gene may affect sensorimotor (exactly as it sounds, both sensory and motor) brain systems.