Excerpt
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder that affects approximately 45% of male and 16% of female carriers of a fragile X mental retardation 1 (
FMR1) gene premutation over the age of 50 years [
1]. Premutations of 55 to 200 CGG repeats of the
FMR1 gene translate into increased
FMR1 mRNA, inducing a toxic gain of function and/or translation of CGG repeats into a polyglycine-containing protein, FMRpolyG [
1,
2]. Notably, almost all premutation carriers with neurological symptoms present with FXTAS and/or have inclusions on autopsy [
3]. Such pathology includes eosinophilic ubiquitin-positive intranuclear inclusions, which contain
FMR1 mRNA and numerous proteins in neurons and astrocytes [
4‐
6]. Defining clinical features of FXTAS include progressive action tremor, gait ataxia, impaired executive function and memory deficits, peripheral neuropathy, and parkinsonism [
1]. Associated variable features include cognitive impairment and dementia; psychiatric symptoms, such as depression; and dysautonomia [
7‐
9]. Radiologically, FXTAS is characterized by progressive global brain atrophy and white matter disease of both the cerebellum and cerebrum [
10,
11]. Importantly, cerebellar and brainstem atrophy and ventricular enlargement are detectable even before the onset of tremor or ataxia [
12,
13]. Currently, no specific treatment for FXTAS can slow the progression of neurodegeneration, though symptomatic treatments exist for some of the symptoms, such as tremor [
14]. Only one previous controlled trial has been performed in individuals with FXTAS, a memantine trial lasting 1 year, but this treatment did not improve tremor, ataxia, or executive function [
15,
16]. …
