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Journal of Neurodevelopmental Disorders

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Open Access 01-12-2019 | Disorders of Intellectual Development | Research

Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers

Authors: Zheng Wang, Pravin Khemani, Lauren M. Schmitt, Su Lui, Matthew W. Mosconi

Published in: Journal of Neurodevelopmental Disorders | Issue 1/2019

Abstract

Background

Individuals with premutation alleles of the fragile X mental retardation 1 (FMR1) gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) during aging. Characterization of motor issues associated with aging in FMR1 premutation carriers is needed to determine neurodegenerative processes and establish new biobehavioral indicators to help identify individuals at greatest risk of developing FXTAS.

Methods

We examined postural stability in 18 premutation carriers ages 46–77 years and 14 age-matched healthy controls. Participants completed a test of static stance and two tests of dynamic postural sway on a force platform to quantify postural variability and complexity. CGG repeat length was measured for each premutation carrier, and MRI and neurological evaluations were conducted to identify carriers who currently met criteria for FXTAS. Of the 18 premutation carriers, seven met criteria for definite/probable FXTAS (FXTAS+), seven showed no MRI or neurological signs of FXTAS (FXTAS−), and four were inconclusive due to insufficient data.

Results

Compared to controls, premutation carriers showed increased center of pressure (COP) variability in the mediolateral (COP_ML) direction during static stance and reduced COP variability in the anterior-posterior (COP_AP) direction during dynamic AP sway. They also showed reductions in COP_ML complexity during each postural condition. FXTAS+ individuals showed reduced COP_AP variability compared to FXTAS− carriers and healthy controls during dynamic AP sway. Across all carriers, increased sway variability during static stance and decreased sway variability in target directions during dynamic sways were associated with greater CGG repeat length and more severe neurologically rated posture and gait abnormalities.

Conclusion

Our findings indicate that aging FMR1 premutation carriers show static and dynamic postural control deficits relative to healthy controls implicating degenerative processes of spinocerebellar and cerebellar-brainstem circuits that may be independent of or precede the onset of FXTAS. Our finding that FXTAS+ and FXTAS− premutation carriers differed on their level of intentional AP sway suggests that neural mechanisms of dynamic postural control may be differentially impacted in patients with FXTAS, and its measurement may be useful for rapidly and precisely identifying disease presence and onset.

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Force

Force is a push or a pull on an object. If the net force on an object is not zero, then the object accelerates (or changes its velocity). Force is a vector and has both magnitude and direction. Force recorded from a force platform includes measurements in three dimensions, including anterior-posterior, mediolateral, and vertical directions. Force along the vertical direction is typically referred to as the ground reaction force.

Moment

The moment is the turning effect produced by a net force perpendicular to the point of rotation.

COP

The point location of the vertical ground reaction force vector. The COP represents a weighted average of pressures over the surface area (i.e., feet) in contact with the ground. It has been used as an indirect measure of individuals’ postural sway. The COP can be derived from the force and moment data collected from a force platform.

COPAP

Center of pressure time series in the anterior-posterior direction.

COPML

Center of pressure time series in the mediolateral direction.

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Title: Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers
Authors: Zheng Wang
Pravin Khemani
Lauren M. Schmitt
Su Lui
Matthew W. Mosconi
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Disorders of Intellectual Development
Tremor
Intellectual Disability
Published in: Journal of Neurodevelopmental Disorders / Issue 1/2019
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI: https://doi.org/10.1186/s11689-018-9261-x

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Springer Medicine

Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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