102 例中国新生儿 Prader-Willi 综合征表型与基因型的关系。

Relationship between phenotype and genotype of 102 Chinese newborns with Prader-Willi syndrome.

机构信息

Department of Neonates, Children's Hospital, Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China.

Department of B Ultrasonography, Children's Hospital, Fudan University, Shanghai, China.

出版信息

Mol Biol Rep. 2019 Oct;46(5):4717-4724. doi: 10.1007/s11033-019-04916-2. Epub 2019 Jul 3.

DOI:10.1007/s11033-019-04916-2

PMID:31270759

Abstract

High rates of misdiagnosis and delayed intervention in neonatal PWS are leading to poor prognoses. To determine the clinical and image characteristics of newborns with Prader-Willi syndrome (PWS). A total of 102 cases of newborns definitively diagnosed with PWS at the Children's Hospital of Fudan University from 02/2014 to 12/2017 were retrospectively analyzed. We analyzed the modulated voxel-based morphology (VBM) of gray matter in PWS by T2 weighted imaging. Of 102 cases, 75 (73.5%) have paternal deletion of 15q11.2-q13, whereas 27 (26.5%) have maternal uniparental disomy (UPD). Of the 75 deletion cases, 75 (100%) week crying, 71 (94.7%) hypotonia, 70 (93.3%) poor feeding, 46 (61.3%) hypopigmentation, 43 (57.3%) male cryptorchidism, 10 (13.3%) female labia minora, 48 (64%) characteristic facial features. Of 27 UPD cases, 27 (100%) week crying and hypotonia, 25 (92.6%) hypophagia, 20 (74.1%) male cryptorchidism, 1 (3.7%) female labia minora, 19 (70.4%) characteristic facial features, 12 (44.4%) hypopigmentation. The modulated VBM analysis shows that the middle frontal gyrus, orbitofrontal cortex (middle), and inferior frontal gyrus are the most variable brain regions that determine the endo-phenotype difference between the two genotypes. Hypotonia, hypophagia, and maldevelopment of sexual organs are general characteristics of newborns with PWS in Chinese population. In UPD cases, the proportions of premature newborns, elderly parturient women and congenital malformations were higher than for paternal deletion cases. The differences in the gray matter volume of these three regions between the two genotypes may explain the differences in maladaptive behaviors and emotions.

摘要

新生儿 PWS 误诊率和干预延迟率高，导致预后不良。为了确定普拉德-威利综合征（PWS）新生儿的临床和影像学特征。对 2014 年 2 月至 2017 年 12 月复旦大学附属儿科医院确诊的 102 例新生儿 PWS 进行回顾性分析。我们通过 T2 加权成像分析了 PWS 患者的灰质调制体素形态学（VBM）。在 102 例中，75 例（73.5%）存在 15q11.2-q13 父源缺失，而 27 例（26.5%）存在母源单亲二体（UPD）。在 75 例缺失病例中，75 例（100%）有哭声微弱，71 例（94.7%）有低张力，70 例（93.3%）有喂养不良，46 例（61.3%）有色素减退，43 例（57.3%）有男性隐睾，10 例（13.3%）有女性小阴唇，48 例（64%）有特征性面部特征。在 27 例 UPD 病例中，27 例（100%）有哭声微弱和低张力，25 例（92.6%）有喂养不良，20 例（74.1%）有男性隐睾，1 例（3.7%）有女性小阴唇，19 例（70.4%）有特征性面部特征，12 例（44.4%）有色素减退。调制 VBM 分析表明，中额回、眶额皮质（中）和下额回是决定两种基因型内表型差异的最可变脑区。低张力、喂养不良和性器官发育不良是中国人群中 PWS 新生儿的共同特征。在 UPD 病例中，早产儿、高龄产妇和先天性畸形的比例高于父源缺失病例。两种基因型之间这三个区域的灰质体积差异可能解释了适应不良行为和情绪的差异。