Centre for Child Health Research, Telethon Institute for Child Health Research, University of Western Australia, Perth, Australia.
Dev Med Child Neurol. 2010 Sep;52(9):817-23. doi: 10.1111/j.1469-8749.2010.03636.x. Epub 2010 Mar 19.
We investigated relationships between hand function and genotype and aspects of phenotype in Rett syndrome.
Video assessment in naturalistic settings was supplemented by parent-reported data in a cross-sectional study of 144 females with a mean age of 14 years 10 months (SD 7 y 10 mo; range 2 y-31 y 10 mo), 110 of whom had a mutation of the methyl CpG binding protein 2 (MECP2) gene. Ordinal logistic regression was used to assess relationships between hand function and MECP2 mutation, age, a modified Kerr score, Functional Independence Measure for Children (WeeFIM), ambulation level, and frequency of hand stereotypies.
Approximately two-thirds of participants demonstrated purposeful hand function, ranging from simple grasping skills to picking up and manipulating small objects. In participants with a confirmed MECP2 mutation, those with the p.R168X mutation had the poorest hand function on multivariate analysis with C-terminal deletion as the baseline (odds ratio [OR] 0.19; 95% confidence interval [CI] 0.04-0.95), whereas those with the p.R133C or p.R294X mutation had better hand function. Participants aged 19 years or older had lower hand function than those aged less than 8 years (OR 0.36; 95% CI 0.14-0.92). Factors that were associated with better hand function were lower Kerr scores for a 1-point increase in score (OR 0.77; 95% CI 0.69-0.86), higher WeeFIM scores for a 1-point increase in score (OR 1.08; 95% CI 1.04-1.12), and greater ambulation than those completely dependent on carers for mobility (OR 22.64; 95% CI 7.02-73.08). The results for participants with a confirmed pathogenic mutation were similar to results obtained when participants without a mutation were also included.
Our novel assessment of hand function in Rett syndrome correlated well with known profiles of common MECP2 mutations and overall clinical severity. This promising assessment could measure clinical responses to therapy.
我们研究了手部功能与基因型以及雷特综合征表型各方面之间的关系。
对 144 名平均年龄为 14 岁 10 个月（标准差 7 岁 10 个月；范围 2 岁-31 岁 10 个月）的女性进行了横断面研究，在自然环境下进行视频评估，并结合家长报告的数据，其中 110 名女性存在甲基 CpG 结合蛋白 2（MECP2）基因突变。采用有序逻辑回归分析手部功能与 MECP2 基因突变、年龄、改良 Kerr 评分、儿童功能性独立评定量表（WeeFIM）、步行水平和手部刻板行为频率之间的关系。
大约三分之二的参与者表现出有目的的手部功能，范围从简单的抓握技能到拿起和操作小物体。在有明确 MECP2 基因突变的参与者中，与 C 端缺失相比，p.R168X 突变的参与者在多变量分析中手部功能最差（比值比 [OR] 0.19；95%置信区间 [CI] 0.04-0.95），而 p.R133C 或 p.R294X 突变的参与者手部功能更好。19 岁或以上的参与者手部功能低于 8 岁以下的参与者（OR 0.36；95% CI 0.14-0.92）。与手部功能较好相关的因素包括：Kerr 评分每增加 1 分（OR 0.77；95% CI 0.69-0.86），WeeFIM 评分每增加 1 分（OR 1.08；95% CI 1.04-1.12），以及步行能力优于完全依赖护理者的参与者（OR 22.64；95% CI 7.02-73.08）。当将无突变的参与者也包括在内时，与已知常见 MECP2 突变和整体临床严重程度相关的结果与我们对手部功能的新评估结果相似。这种有前景的评估方法可以衡量治疗的临床反应。
