Characterization of Fine Motor and Visual Motor Skills in Aicardi-Goutières Syndrome

Abstract

Aicardi-Goutières syndrome is a genetic inflammatory disorder resulting in dispersed neurologic dysfunction. Despite a recognition of overall motor impairment, fine and visual motor skills are undercharacterized. We hypothesize that there is a spectrum of fine and visual motor skills in the Aicardi-Goutières syndrome population as captured by a standard outcome measure, the Peabody Developmental Motor Scales (PDMS-2), which will be proportional to overall disease severity.In a cohort of 74 subjects, the Peabody Developmental Motor Scales-2 grasping and visual-motor integration subtests were administered concurrently with the Aicardi-Goutières syndrome Severity Scale (severe [range 0-3], moderate [range 4-8], and attenuated [range 9-11]). The cohort was also compared by genotype and performance as defined by raw scores. The distribution of Peabody Developmental Motor Scales-2 scores within a genotype was assessed by interquartile ranges (IQRs).Peabody Developmental Motor Scales-2 grasping and visual-motor integration performance was the least variable in the TREX1-cohort (IQR: 10.00-12.00) versus the SAMHD1 and IFIH1 cohorts (IQR: 51.00-132.00 and 48.50-134.00, respectively). Neurologic severity highly correlated with both fine and visual motor skills (Spearman correlation: r = 0.87, 0.91, respectively). A floor effect (lowest 10% of possible scores) was observed within the severe cohort (n = 32/35), whereas a ceiling effect (top 10%) was observed in the attenuated cohort (n = 13/17).This study characterized the spectrum of fine and visual motor function in the Aicardi-Goutières syndrome population, which correlated with overall neurologic dysfunction. The Peabody Developmental Motor Scales-2 grasping and visual-motor integration showed promise as potential assessment tools in moderate and attenuated Aicardi-Goutières syndrome cohorts. A better understanding of fine and visual motor function in this population will benefit clinical care and clinical trial design.

Keywords: developmental delay; leukodystrophy; outcome; pediatric.

Figure 1.

Assessment of fine motor function in AGS by PDMS-2. Each individual is represented by a single dot. A. Grasping subtest shows performance heterogeneity within our cohort. TREX1 and RNASEH2 subgroups had the lowest performance as expressed by median scores, while SAMHD1 and IFIH1 subgroups had the highest variability by IQR. Left Y axis plots subtest raw scores, right Y axis represents age equivalents. B. VMI subtest shows performance heterogeneity within our cohort. TREX1 and RNASEH2 subgroups had the lowest performance as expressed by median scores, while SAMHD1 and IFIH1 subgroups had the highest variability by IQR. Left Y axis plots subtest raw scores, right Y axis represents age equivalents.

Figure 2.

Performance at the PDMS-2 by disease severity. Disease severity is defined by AGS scores, with the generation of three severity categories (severe for AGS scores range 0–3, moderate for AGS scores range 4–8, attenuated for AGS scores range 9–11). A. PDMS-2 Grasping subtest performance was significantly different between the three cohorts (Kruskal-Wallis test with Dunn’s test for multiple comparisons, p<0.0001: severe vs moderate p<0.0001, moderate vs attenuated p=0.0071, severe vs attenuated <0.0001). Floor effect performance was observed within the severe group, while ceiling effect was observed within the attenuated group. B. PDMS-2 VMI subtest performance was significantly different between the three cohorts (Kruskal-Wallis test with Dunn’s test for multiple comparisons, p<0.0001: severe vs moderate p<0.0001, moderate vs attenuated p=0.0123, severe vs attenuated <0.0001). Floor effect performance was observed within the severe group, while ceiling effect was observed within the attenuated group.