Neuroanatomical phenotype of Klinefelter syndrome in childhood: a voxel-based morphometry study.
Neuroanatomical phenotype of Klinefelter syndrome in childhood: a voxel-based morphometry study.
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DOI：
10.1523/jneurosci.5899-10.2011
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发表时间：
2011-05-04
期刊：
影响因子：
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通讯作者：
Reiss AL
中科院分区：
文献类型：
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作者：
Bryant DM;Hoeft F;Lai S;Lackey J;Roeltgen D;Ross J;Reiss AL
Klinefelter综合征（KS）是一种遗传性疾病，其特征是额外的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个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异，但在受试者纳入标准方面存在很大差异，包括镶嵌性、青春期状态和睾酮替代治疗（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岁± SD：1.70）和36名典型发育（TD）男性对照（10.99 ± 1.72）进行了基于体素的区域灰质和白色物质体积的形态测定（VBM）研究。所有KS患者均未接受过TRT治疗，且均为青春期前，核型均为非嵌合体47，XXY。在控制年龄后，KS男性显示出相对于TD男性显著减少的总灰质体积（TGMV）和总白色体积（TWMV）的趋势（0.05<p<0.10）。在控制了TGMV和年龄后，KS组的感觉运动和顶枕GM显著增加，杏仁核、海马、岛叶、颞叶和下额叶GM显著减少。在控制TWMV和年龄后，KS组左顶叶WM显著增加，额叶和颞叶WM显著减少。这些结果表明，一个特征性的青春期前神经解剖表型，可能与KS的认知行为特征。这项工作为X染色体基因表达，神经解剖学和KS中受损的认知行为功能（包括语言和注意力）之间的关系提供了新的见解。
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 reveal neuroanatomical variations associated with KS, but differ 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 (VBM) study of regional grey and white matter volumes in 31 KS males (mean age: 9.69 years ± SD: 1.70) and 36 typically developing (TD) male controls (10.99 ± 1.72). None of the participants with KS had received TRT, and all were prepubertal and had non-mosaic 47, XXY karyotypes. After controlling for age, males with KS showed trends (0.05<p<0.10) for significantly reduced total grey 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.