A Quantitative Assessment of Tremor and Ataxia in FemaleFMR1Premutation Carriers Using CATSYS

Vivien Narcisa,Luis Campos,Patrick Adams,Shana White,Danh V Nguyen,Randi J Hagerman,Paul J Hagerman,Jeffrey Brodovsky,Flora Tassone,Dalila Aguilar

doi:10.1155/2011/484713

Abstract

The fragile X-associated tremor/ataxia syndrome (FXTAS) is a relatively common cause of balance problems leading to gait disturbances in older males (40%) with the premutation. FXTAS is less common in females. We utilized the CATSYS system, a quantitative measure of movement, in 23 women with FXTAS (mean age 62.7; SD 12.3), 90 women with the premutation without FXTAS (mean age 52.9; SD 9.4), and 37 controls (mean age 56.53; SD 7.8). CATSYS distinguished differences between carriers with and without FXTAS in postural tremor, postural sway, hand coordination, and reaction time tasks. Differences were also seen between carriers without FXTAS and controls in finger tapping, reaction time, and one postural sway task. However, these differences did not persist after statistical correction for multiple comparisons. Notably, there were no differences across groups in intention tremor. This is likely due to the milder symptoms in females compared to males with FXTAS.

Highlights

Fragile X-associated tremor/ataxia syndrome (FXTAS) is caused by the premutation (55–200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene
There were no differences in FMR1 expression, CGG, and activation ratio (AR) between premutation carriers with and without fragile X-associated tremor/ataxia syndrome (FXTAS)
Our findings demonstrate significant differences between those with FXTAS compared to controls, including postural sway, postural hand tremor intensity, and finger tapping

Summary

Introduction

Fragile X-associated tremor/ataxia syndrome (FXTAS) is caused by the premutation (55–200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. Core symptoms of FXTAS include tremor and ataxia, the syndrome includes autonomic dysfunction, neuropathy, psychopathology, executive function deficits, and cognitive decline [1,2,3]. The premutation expansion is associated with elevated FMR1 mRNA that leads to a gain-of-function toxicity in neurons and astrocytes [4,5,6,7,8]. MRI findings include global brain atrophy and white matter disease in the middle cerebellar peduncles (MCPs), pons, periventricular area, subcortical regions, and insula, and on neuropathological assessment there are eosinophilic inclusions in neurons and astrocytes caused by the elevated levels of FMR1-mRNA [1, 12, 13]

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