Background: Aicardi-Goutières syndrome (AGS) is a rare genetic disorder characterized by a spectrum of motor abilities. While the Aicardi-Goutières syndrome severity score favors severely impacted individuals, there is an unmet need to define tools measuring function across the Aicardi-Goutières syndrome spectrum as potential outcome assessments for future clinical trials. Methods: Gross Motor Function Measure-88 (GMFM-88) and AGS Severity Scale were administered in individuals affected by Aicardi-Goutières syndrome (n = 71). We characterized the performance variability by genotype. Derived versions of the GMFM-88, including the GMFM-66, GMFM-66 item set (GMFM-66IS), and GMFM-66 Basal&Ceiling (GMFM-66BC) were calculated. The Aicardi-Goutières syndrome cohort was divided into severe (AGS Severity Scale score <4) or attenuated (≥4). Performance on the AGS Severity Scale highly correlated with total GMFM-88 scores (Spearman Correlation: R = 0.91). To assess variability of the GMFM-88 within genotypic subcohorts, interquartile ranges (IQRs) were compared. Results: GMFM-88 performance in the TREX1 cohort had least variability while the SAMHD1 cohort had the largest IQR (4.23 vs 81.8). Floor effect was prominent, with most evaluations scoring below 20% (n = 46, 64.79%), particularly in TREX1- and RNASEH2-cohorts. Performance by the GMFM-66, GMFM-66IS, and GMFM-66BC highly correlated with the full GMFM-88. The Aicardi-Goutières syndrome population represents a broad range of gross motor skills. Conclusions: This work identified the GMFM-88 as a potential clinical outcome assessment in subsets of the Aicardi-Goutières syndrome population but underscores the need for additional validation of outcome measures reflective of the diverse gross motor function observed in this population, including low motor function. When time is limited by resources or patient endurance, shorter versions of the GMFM-88 may be a reasonable alternative.

中文翻译：

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Aicardi-Goutières 综合征粗大运动功能的探索。

背景：Aicardi-Goutières 综合征 (AGS) 是一种罕见的遗传性疾病，其特征是一系列运动能力。虽然 Aicardi-Goutières 综合征严重程度评分有利于受影响严重的个体，但仍需要定义测量 Aicardi-Goutières 综合征谱系功能的工具，作为未来临床试验的潜在结果评估。方法：对 Aicardi-Goutières 综合征患者 (n = 71) 进行粗大运动功能测量 88 (GMFM-88) 和 AGS 严重程度量表。我们通过基因型来表征性能变异性。计算了 GMFM-88 的派生版本，包括 GMFM-66、GMFM-66 项目集 (GMFM-66IS) 和 GMFM-66 Basal&Ceiling (GMFM-66BC)。Aicardi-Goutières 综合征队列被分为严重（AGS 严重程度量表评分 <4）或减弱（≥4）。AGS 严重程度量表的表现与 GMFM-88 总分高度相关（Spearman 相关性：R = 0.91）。为了评估基因型亚群内 GMFM-88 的变异性，比较了四分位数间距 (IQR)。结果：TREX1 队列中的 GMFM-88 表现变异性最小，而 SAMHD1 队列的 IQR 最大（4.23 vs 81.8）。地板效应很明显，大多数评估得分低于 20%（n = 46, 64.79%），特别是在 TREX1 和 RNASEH2 队列中。GMFM-66、GMFM-66IS 和 GMFM-66BC 的性能与完整的 GMFM-88 高度相关。Aicardi-Goutières 综合征人群代表了广泛的粗大运动技能。结论：这项工作将 GMFM-88 确定为 Aicardi-Goutières 综合征人群子集的潜在临床结果评估，但强调需要对反映该人群中观察到的不同粗大运动功能（包括低运动功能）的结果测量进行额外验证。当时间受到资源或患者耐力的限制时，较短版本的 GMFM-88 可能是一个合理的替代方案。