Department of Occupational Therapy, University of Florida, Gainesville, FL, 32611, USA.
University of Florida, 1225 Center Drive, PO Box 100164, Gainesville, FL, 326100164, USA.
J Neurodev Disord. 2019 Jan 21;11(1):2. doi: 10.1186/s11689-018-9261-x.
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) direction during static stance and reduced COP variability in the anterior-posterior (COP) direction during dynamic AP sway. They also showed reductions in COP complexity during each postural condition. FXTAS+ individuals showed reduced COP 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.
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.
脆性 X 智力低下 1 号基因（FMR1）前突变等位基因的个体在衰老过程中易患脆性 X 相关震颤共济失调综合征（FXTAS）。需要对 FMR1 前突变携带者衰老相关的运动问题进行特征描述，以确定神经退行性过程并建立新的生物行为指标，帮助识别最有可能发展为 FXTAS 的个体。
我们检查了 18 名年龄在 46-77 岁的前突变携带者和 14 名年龄匹配的健康对照者的姿势稳定性。参与者在力平台上完成静态站立测试和两种动态姿势摆动测试，以量化姿势变异性和复杂性。对每个前突变携带者测量 CGG 重复长度，并进行 MRI 和神经学评估，以确定目前符合 FXTAS 标准的携带者。在 18 名前突变携带者中，有 7 名符合明确/可能 FXTAS（FXTAS+）标准，7 名无 FXTAS 的 MRI 或神经学迹象（FXTAS-），4 名因数据不足而不确定。
与对照组相比，前突变携带者在静态站立时的中压（COP）变异性增加，在动态前后（COP）摆动时的 COP 变异性减小。他们在每个姿势条件下的 COP 复杂性也降低了。与 FXTAS-携带者和健康对照组相比，FXTAS+个体在动态前后摆动时的 COP 变异性降低。在所有携带者中，静态站立时的摆动变异性增加和动态摆动时目标方向的摆动变异性减小与更大的 CGG 重复长度和更严重的神经学评定姿势和步态异常相关。
我们的研究结果表明，衰老的 FMR1 前突变携带者相对于健康对照组表现出静态和动态姿势控制缺陷，这表明与小脑和小脑脑桥回路的退行性过程有关，这些过程可能独立于或先于 FXTAS 的发生。我们发现 FXTAS+和 FXTAS-前突变携带者在他们的有意前后摆动水平上有所不同，这表明动态姿势控制的神经机制可能在 FXTAS 患者中受到不同的影响，其测量可能有助于快速、准确地识别疾病的存在和发作。
