威廉姆斯综合征的产前诊断及表型分析

Prenatal diagnosis and literature review of fetal phenotypes of Williams-Beuren syndrome

目的分析威廉姆斯综合征(Williams-Beuren syndrome,WBS)胎儿的基因型及表型相关性,为精准产前诊断及产前遗传咨询WBS胎儿提供帮助。方法对深圳市龙岗区妇幼保健院进行产前诊断的产前诊断的孕妇进行染色体微阵列分析(chromosomal microarray analysis,CMA)检测,同时查询关于WBS产前诊断已发表的文献,结合CMA结果及胎儿超声信息开展分析。结果(1)本研究共在1574例产前诊断羊水标本中诊断出4例7q11.23微缺失病例,CNV片段大小介于1.43~1.66Mb,符合经典的WBS缺失范围;(2)对缺失CNV包含基因分析显示,缺失的基因数从35个到41个,所有缺失均包含ELN基因;(3)1例存在明显的肺动脉异常,1例胎儿超声显示多囊性肾发育不良合并三尖瓣少量反流,2例胎儿没有明显的超声异常,仅是因NIPT高风险进行产前诊断,其中一例超声提示左心强光点;(4)查询文献,对98例产前诊断的胎儿WBS超声情况分析,最常见的超声表型是胎儿宫内发育迟缓(59.8%,58/98),心血管异常(39.8%,39/98),羊水过多(12.24%,12/98),胎儿股骨长度偏短(11.22%,11/98),另外胎儿多囊肾检出率约3.06%(3/98)。结论WBS胎儿在产前存在不典型超声表型的情况,甚至部分胎儿在孕早期没有明显的超声异常,综合NIPT等其他筛查方法有助于早期诊断胎儿WBS疾病。

Objective To analyze the genotypic and phenotypic correlation of fetuses with WilliamsBeuren syndrome(WBS)and to provide guidelines for accurate prenatal diagnosis and genetic counseling of WBS fetuses.Methods Chromosomal microarray analysis(CMA)was performed on pregnant women undergoing prenatal diagnosis,while the published literature on prenatal diagnosis of WBS was searched and the results of CMA and fetal ultrasound information were analyzed.Results 4cases of 7q11.23microdeletion were diagnosed in 1574prenatal diagnostic samples,and the size of CNV fragments ranged from 1.43to 1.66Mb,affecting 35to 41genes,respectively,and all deletions contained ELN genes;1case had anomaly of the pulmonary artery,1case showed polycystic kidney dysplasia combined with a small degree of tricuspid regurgitation,and two fetuses had no significant ultrasound abnormalities and were only diagnosed prenatally only because of high risk for NIPT.Literature review and analysis of the ultrasound status of 98prenatally diagnosed fetuses with WBS revealed that the most common ultrasound phenotypes were intrauterine growth retardation(59.8%,58/98),cardiovascular anomalies(39.8%),polyhydramnios(12.24%,12/98),and short femur length(11.22%,11/98),in addition,the detection rate of fetal polycystic kidney in WBS is approximately 3.06%(3/98).Conclusion The ultrasound phenotype of WBS fetuses in the prenatal period maybe atypical,or even some fetuses do not have obvious ultrasound abnormalities in early pregnancy,and a combination of other factors,such as NIPT,may be helpful in the early diagnosis of fetal WBS disease.