Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305-5795, USA.
J Neurosci. 2011 May 4;31(18):6654-60. doi: 10.1523/JNEUROSCI.5899-10.2011.
Klinefelter syndrome (KS) is a genetic disorder characterized by a supernumerary X chromosome. As such, KS offers a naturally occurring human model for the study of both X-chromosome gene expression and androgen on brain development. Previous neuroimaging studies have revealed neuroanatomical variations associated with KS, but have differed widely with respect to subject inclusion criteria, including mosaicism, pubertal status, and history of testosterone replacement therapy (TRT), all factors likely to influence neurodevelopment. We conducted a voxel-based morphometry study of regional gray and white matter (GM and WM, respectively) volumes in 31 KS males (mean age, 9.69 ± 1.70 years) and 36 typically developing (TD) male controls (10.99 ± 1.72 years). None of the participants with KS had received TRT, and all were prepubertal and had nonmosaic 47,XXY karyotypes. After controlling for age, males with KS showed trends (0.05 < p < 0.10) for significantly reduced total gray matter volume (TGMV) and total white matter volume (TWMV), relative to TD males. After controlling for TGMV and age, the KS group had significantly increased sensorimotor and parietal-occipital GM and significantly reduced amygdalar, hippocampal, insular, temporal, and inferior frontal GM relative to TD controls. After controlling for TWMV and age, the KS group had significantly increased left parietal WM as well as significantly reduced frontal and temporal WM. These findings are indicative of a characteristic prepubertal neuroanatomical phenotype that may be associated with cognitive-behavioral features of KS. This work offers new insight into the relationships among X-chromosome gene expression, neuroanatomy, and cognitive-behavioral functions impaired in KS, including language and attention.
克莱恩费尔特综合征（KS）是一种遗传性疾病，其特征是存在额外的 X 染色体。因此，KS 为研究 X 染色体基因表达和雄激素对大脑发育的影响提供了一种自然发生的人类模型。先前的神经影像学研究揭示了与 KS 相关的神经解剖学变化，但在纳入标准方面存在广泛差异，包括嵌合体、青春期状态和睾酮替代疗法（TRT）史，所有这些因素都可能影响神经发育。我们对 31 名 KS 男性（平均年龄 9.69 ± 1.70 岁）和 36 名正常发育男性对照者（10.99 ± 1.72 岁）的局部灰质和白质（GM 和 WM）体积进行了基于体素的形态计量学研究。KS 组中没有接受 TRT 的参与者，所有参与者均处于青春期前，核型均为非嵌合 47,XXY。在控制年龄后，KS 男性的总灰质体积（TGMV）和总白质体积（TWMV）相对于 TD 男性呈显著降低趋势（0.05 < p < 0.10）。在控制 TGMV 和年龄后，KS 组的感觉运动和顶枕部 GM 增加，杏仁核、海马、岛叶、颞叶和额下回 GM 减少。在控制 TWMV 和年龄后，KS 组左侧顶叶 WM 增加，额叶和颞叶 WM 减少。这些发现表明，在青春期前可能与 KS 的认知行为特征相关的神经解剖学表型存在特征性。这项工作为研究 X 染色体基因表达、神经解剖学和 KS 受损的认知行为功能之间的关系提供了新的见解，包括语言和注意力。
