Treatment of fragile X-associated tremor ataxia syndrome (FXTAS) and related neurological problems

Randi J Hagerman^1,2, Deborah A Hall³, Sarah Coffey^1,2, Maureen Leehey³, James Bourgeois⁴, John Gould⁵, Lin Zhang⁶, Andreea Seritan⁴, Elizabeth Berry-Kravis^7–9, John Olichney⁶, Joshua W Miller¹⁰, Amy L Fong¹¹, Randall Carpenter¹², Cathy Bodine¹³, Louise W Gane^1,2, Edgar Rainin¹, Hillary Hagerman¹, Paul J Hagerman¹⁴

¹M.I.N.D. Institute, ²Department of Pediatrics, ⁴Department of Psychiatry & Behavioral Sciences, ⁵Department of Urology, ⁶Department of Neurology, ¹⁰Department of Pathology and Laboratory Medicine, ¹⁴Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, CA, USA; ³Department of Neurology, University of Colorado, Denver, CO, USA; ⁷Department of Pediatrics, Neurology, and Biochemistry, ⁸Department of Neurological Sciences, ⁹Department of Biochemistry, Rush University Medical Center, Chicago, IL, USA; ¹¹Physical Edge, Inc., Davis, CA, USA; ¹²Seaside Therapeutics, Cambridge, MA, USA; ¹³Department of Physical Medicine and Rehabilitation, University of Colorado Health Sciences Center, Denver, CO, USA

Abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurological disorder that affects older adult carriers, predominantly males, of premutation alleles (55 to 200 CGG repeats) of the fragile X (FMR1) gene. Principal features of FXTAS are intention tremor, ataxia, parkinsonism, cognitive decline, and peripheral neuropathy; ancillary features include, autonomic dysfunction, and psychiatric symptoms of anxiety, depression, and disinhibition. Although controlled trials have not been carried out in individuals with FXTAS, there is a significant amount of anecdotal information regarding various treatment modalities. Moreover, there exists a great deal of evidence regarding the efficacy of various medications for treatment of other disorders (eg, Alzheimer disease) that have substantial phenotypic overlap with FXTAS. The current review summarizes what is currently known regarding the symptomatic treatment, or potential for treatment, of FXTAS.

Keywords: fragile X syndrome, dementia, ataxia, neurodegeneration, parkinsonism, tremor