Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers
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 dete...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-01-01
|
| Series: | Journal of Neurodevelopmental Disorders |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s11689-018-9261-x |
| _version_ | 1818554626932211712 |
|---|---|
| author | Zheng Wang Pravin Khemani Lauren M. Schmitt Su Lui Matthew W. Mosconi |
| author_facet | Zheng Wang Pravin Khemani Lauren M. Schmitt Su Lui Matthew W. Mosconi |
| author_sort | Zheng Wang |
| collection | DOAJ |
| description | 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 (COPML) direction during static stance and reduced COP variability in the anterior-posterior (COPAP) direction during dynamic AP sway. They also showed reductions in COPML complexity during each postural condition. FXTAS+ individuals showed reduced COPAP 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. |
| first_indexed | 2024-12-12T09:42:27Z |
| format | Article |
| id | doaj.art-2f089908c71348c9b1f24f747f009e73 |
| institution | Directory Open Access Journal |
| issn | 1866-1947 1866-1955 |
| language | English |
| last_indexed | 2024-12-12T09:42:27Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neurodevelopmental Disorders |
| spelling | doaj.art-2f089908c71348c9b1f24f747f009e732022-12-22T00:28:31ZengBMCJournal of Neurodevelopmental Disorders1866-19471866-19552019-01-0111111310.1186/s11689-018-9261-xStatic and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriersZheng Wang0Pravin Khemani1Lauren M. Schmitt2Su Lui3Matthew W. Mosconi4Department of Occupational Therapy, University of FloridaDepartment of Neurology, Swedish Neuroscience InstituteDivision of Developmental and Behavioral Pediatrics, Cincinnati Children’s Hospital Medical CenterHuaxi Magnetic Resonance Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan UniversitySchiefelbusch Institute for Life Span Studies, University of KansasAbstract 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 (COPML) direction during static stance and reduced COP variability in the anterior-posterior (COPAP) direction during dynamic AP sway. They also showed reductions in COPML complexity during each postural condition. FXTAS+ individuals showed reduced COPAP 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.http://link.springer.com/article/10.1186/s11689-018-9261-xFragile X mental retardation 1 (FMR1) geneFMR1gene premutation alleleFragile X-associated tremor/ataxia syndrome (FXTAS)Postural controlCerebellum |
| spellingShingle | Zheng Wang Pravin Khemani Lauren M. Schmitt Su Lui Matthew W. Mosconi Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers Journal of Neurodevelopmental Disorders Fragile X mental retardation 1 (FMR1) gene FMR1gene premutation allele Fragile X-associated tremor/ataxia syndrome (FXTAS) Postural control Cerebellum |
| title | Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers |
| title_full | Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers |
| title_fullStr | Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers |
| title_full_unstemmed | Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers |
| title_short | Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers |
| title_sort | static and dynamic postural control deficits in aging fragile x mental retardation 1 fmr1 gene premutation carriers |
| topic | Fragile X mental retardation 1 (FMR1) gene FMR1gene premutation allele Fragile X-associated tremor/ataxia syndrome (FXTAS) Postural control Cerebellum |
| url | http://link.springer.com/article/10.1186/s11689-018-9261-x |
| work_keys_str_mv | AT zhengwang staticanddynamicposturalcontroldeficitsinagingfragilexmentalretardation1fmr1genepremutationcarriers AT pravinkhemani staticanddynamicposturalcontroldeficitsinagingfragilexmentalretardation1fmr1genepremutationcarriers AT laurenmschmitt staticanddynamicposturalcontroldeficitsinagingfragilexmentalretardation1fmr1genepremutationcarriers AT sului staticanddynamicposturalcontroldeficitsinagingfragilexmentalretardation1fmr1genepremutationcarriers AT matthewwmosconi staticanddynamicposturalcontroldeficitsinagingfragilexmentalretardation1fmr1genepremutationcarriers |