Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers.
Aged
Aging
/ genetics
Ataxia
/ diagnostic imaging
Biomechanical Phenomena
Cerebellum
/ diagnostic imaging
Female
Fragile X Mental Retardation Protein
/ genetics
Fragile X Syndrome
/ diagnostic imaging
Heterozygote
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Postural Balance
/ genetics
Tremor
/ diagnostic imaging
Trinucleotide Repeat Expansion
/ genetics
Cerebellum
FMR1gene premutation allele
Fragile X mental retardation 1 (FMR1) gene
Fragile X-associated tremor/ataxia syndrome (FXTAS)
Postural control
Journal
Journal of neurodevelopmental disorders
ISSN: 1866-1955
Titre abrégé: J Neurodev Disord
Pays: England
ID NLM: 101483832
Informations de publication
Date de publication:
21 01 2019
21 01 2019
Historique:
received:
05
09
2018
accepted:
26
12
2018
entrez:
23
1
2019
pubmed:
23
1
2019
medline:
4
8
2020
Statut:
epublish
Résumé
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. 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. Compared to controls, premutation carriers showed increased center of pressure (COP) variability in the mediolateral (COP 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.
Sections du résumé
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
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.
Identifiants
pubmed: 30665341
doi: 10.1186/s11689-018-9261-x
pii: 10.1186/s11689-018-9261-x
pmc: PMC6341725
doi:
Substances chimiques
FMR1 protein, human
0
Fragile X Mental Retardation Protein
139135-51-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2Subventions
Organisme : National Institute of Child Health and Human Development
ID : U54HD090216
Pays : International
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