Brain Imaging, Development and Genetics Lab, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California; Division of Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
Division of Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California; Brain Dynamics Lab, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Feb;9(2):146-155. doi: 10.1016/j.bpsc.2022.08.012. Epub 2022 Sep 7.
Turner syndrome (TS) and Noonan syndrome (NS) are distinct genetic conditions with highly similar physical and neurodevelopmental phenotypes. TS is caused by X chromosome absence, whereas NS results from genetic mutations activating the Ras-mitogen-activated protein kinase signaling pathway. Previous neuroimaging studies in individuals with TS and NS have shown neuroanatomical variations relative to typically developing individuals, a standard comparison group when initially examining a clinical group of interest. However, none of these studies included a second clinical comparison group, limiting their ability to identify syndrome-specific neuroanatomical phenotypes.
In this study, we compared the behavioral and brain phenotypes of 37 girls with TS, 26 girls with NS, and 37 typically developing girls, all ages 5 to 12 years, using univariate and multivariate data-driven analyses.
We found divergent neuroanatomical phenotypes between groups, despite high behavioral similarities. Relative to the typically developing group, TS was associated with smaller whole-brain cortical surface area (p ≤ .0001), whereas NS was associated with smaller whole-brain cortical thickness (p = .013). TS was associated with larger subcortical volumes (left amygdala, p = .002; right hippocampus, p = .002), whereas NS was associated with smaller subcortical volumes (bilateral caudate, p ≤ .003; putamen, p < .001; pallidum, p < .001; right hippocampus, p = .015). Multivariate analyses also showed diverging brain phenotypes in terms of surface area and cortical thickness, with surface area outperforming cortical thickness at group separation.
TS and NS have syndrome-specific brain phenotypes, despite their behavioral similarities. Our observations suggest that neuroanatomical phenotypes better reflect the different genetic etiologies of TS and NS and may be superior biomarkers relative to behavioral phenotypes.
特纳综合征（TS）和努南综合征（NS）是两种截然不同的遗传疾病，具有高度相似的身体和神经发育表型。TS 是由 X 染色体缺失引起的，而 NS 则是由于激活 Ras-丝裂原活化蛋白激酶信号通路的基因突变所致。先前对 TS 和 NS 个体的神经影像学研究表明，与典型发育个体相比，存在神经解剖学差异，而典型发育个体是在最初检查感兴趣的临床群体时的标准对照群体。然而，这些研究中没有一项包括第二个临床对照群体，这限制了他们识别综合征特异性神经解剖表型的能力。
在这项研究中，我们使用单变量和多变量数据驱动分析比较了 37 名 TS 女孩、26 名 NS 女孩和 37 名典型发育女孩的行为和大脑表型，所有女孩年龄在 5 至 12 岁之间。
尽管行为高度相似，但我们发现组间存在不同的神经解剖表型。与典型发育组相比，TS 与全脑皮质表面积减小有关（p ≤.0001），而 NS 与全脑皮质厚度减小有关（p =.013）。TS 与较大的皮质下体积有关（左侧杏仁核，p =.002；右侧海马体，p =.002），而 NS 与较小的皮质下体积有关（双侧尾状核，p ≤.003；壳核，p <.001；苍白球，p <.001；右侧海马体，p =.015）。多变量分析还显示，在表面积和皮质厚度方面存在不同的大脑表型，表面积在组间分离方面优于皮质厚度。
尽管 TS 和 NS 的行为相似，但它们具有综合征特异性的大脑表型。我们的观察结果表明，神经解剖学表型更好地反映了 TS 和 NS 的不同遗传病因，并且可能优于行为表型，成为更好的生物标志物。
