Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Pediatrics, Chiba University Hospital, Chiba-shi, Chiba, Japan.
Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Mathematics, Statistics and Computer Science, St. Francis Xavier University, Antigonish, Nova Scotia, Canada.
Pediatr Neurol. 2019 Nov;100:67-73. doi: 10.1016/j.pediatrneurol.2019.03.015. Epub 2019 Mar 22.
Down syndrome (DS) is the most prevalent chromosomal disorder characterized by intellectual disability, multiple organ anomalies, generalized muscular hypotonia, and characteristic physical features. The presence of DS-associated medical comorbidities has contributed to brain morphologic changes. The aim of this study was to evaluate brain morphologic characteristics during infant and toddler ages in patients with DS using structural brain magnetic resonance imaging.
Structural brain T1-weighted magnetic resonance images from participants with DS with complete chromosome 21 trisomy (n = 20; 1.6 ± 0.6 [mean ± standard deviation] years old) were analyzed using FreeSurfer. The measurements were compared with those of 60 gender- and age-matched neurotypical controls by Cohen's d statistic and unpaired t test with false discovery rate correction for multiple comparisons and analyzed using a univariate general linear model with the following DS-associated medical comorbidities: congenital cardiac disease, infantile spasms, and hypothyroidism.
We identified 27 candidate measurements with large effect sizes (absolute d > 0.8) and statistically significant differences (P < 6.9 × 10). Among them were decreased volumes in bilateral cerebellar gray matter and right cerebellar white matter and brainstem and cortical abnormalities in the right superior temporal, right rostral anterior cingulate, and left rostral middle frontal gyrus, independent of comorbid effects. Only bilateral cerebellar gray matter volumes and brainstem volume showed differences between DS and healthy groups during infancy.
These results suggest that cerebellar gray matter and brainstem may represent the primary regions affected by the presence of an additional copy of chromosome 21.
唐氏综合征（DS）是最常见的染色体疾病，其特征为智力障碍、多种器官异常、全身肌肉张力减退和典型的身体特征。DS 相关的合并症的存在导致了大脑形态变化。本研究旨在使用结构脑磁共振成像评估 DS 患者在婴儿和幼儿期的大脑形态特征。
使用 FreeSurfer 分析 20 名患有完全 21 三体的 DS 患者（1.6 ± 0.6[均数 ± 标准差]岁）的结构脑 T1 加权磁共振图像。采用 Cohen's d 统计量和未配对 t 检验与虚假发现率校正多重比较，将测量值与 60 名性别和年龄匹配的神经典型对照组进行比较，并使用单变量一般线性模型分析与 DS 相关的合并症：先天性心脏病、婴儿痉挛和甲状腺功能减退。
我们确定了 27 个候选测量值，具有较大的效应大小（绝对值 d > 0.8）和统计学差异（P < 6.9×10）。其中包括双侧小脑灰质和右侧小脑白质以及右侧颞上回、右侧额前扣带回和左侧额中回皮质异常的体积减少，与合并症无关。只有双侧小脑灰质体积和脑干体积在婴儿期在 DS 和健康组之间存在差异。
这些结果表明，小脑灰质和脑干可能是由于额外的 21 号染色体拷贝存在而受影响的主要区域。
