Green Tamar, Fierro Kyle C, Raman Mira M, Saggar Manish, Sheau Kristen E, Reiss Allan L
Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, California.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Am J Med Genet B Neuropsychiatr Genet. 2016 Apr;171B(3):402-13. doi: 10.1002/ajmg.b.32422. Epub 2016 Feb 7.
Morphometric investigations of brain volumes in Williams syndrome (WS) consistently show significant reductions in gray matter volume compared to controls. Cortical thickness (CT) and surface area (SA) are two constituent parts of cortical gray matter volume that are considered genetically distinguishable features of brain morphology. Yet, little is known about the independent contribution of cortical CT and SA to these volumetric differences in WS. Thus, our objectives were: (i) to evaluate whether the microdeletion in chromosome 7 associated with WS has a distinct effect on CT and SA, and (ii) to evaluate age-related variations in CT and SA within WS. We compared CT and SA values in 44 individuals with WS to 49 age- and sex-matched typically developing controls. Between-group differences in CT and SA were evaluated across two age groups: young (age range 6.6-18.9 years), and adults (age range 20.2-51.5 years). Overall, we found contrasting effects of WS on cortical thickness (increases) and surface area (decreases). With respect to brain topography, the between-group pattern of CT differences showed a scattered pattern while the between-group surface area pattern was widely distributed throughout the brain. In the adult subgroup, we observed a cluster of increases in cortical thickness in WS across the brain that was not observed in the young subgroup. Our findings suggest that extensive early reductions in surface area are the driving force for the overall reduction in brain volume in WS. The age-related cortical thickness findings might reflect delayed or even arrested development of specific brain regions in WS.
对威廉姆斯综合征(WS)患者脑容量的形态学研究始终表明,与对照组相比,其灰质体积显著减少。皮质厚度(CT)和表面积(SA)是皮质灰质体积的两个组成部分,被认为是脑形态学的遗传可区分特征。然而,关于皮质CT和SA对WS中这些体积差异的独立贡献知之甚少。因此,我们的目标是:(i)评估与WS相关的7号染色体微缺失是否对CT和SA有独特影响,以及(ii)评估WS中CT和SA与年龄相关的变化。我们将44名WS患者的CT和SA值与49名年龄和性别匹配的正常发育对照者进行了比较。在两个年龄组中评估了CT和SA的组间差异:年轻组(年龄范围6.6 - 18.9岁)和成年组(年龄范围20.2 - 51.5岁)。总体而言,我们发现WS对皮质厚度(增加)和表面积(减少)有相反的影响。关于脑地形图,CT差异的组间模式呈散在分布,而组间表面积模式则广泛分布于整个大脑。在成年亚组中,我们观察到WS患者大脑皮质厚度有一组增加,而在年轻亚组中未观察到。我们的研究结果表明,早期广泛的表面积减少是WS患者脑容量总体减少的驱动力。与年龄相关的皮质厚度研究结果可能反映了WS患者特定脑区发育延迟甚至停滞。