46例22q11.2微缺失综合征胎儿心脏超声特征及临床表型

Fetal echocardiographic features and clinical phenotype of 22q11.2 microdeletion syndrome:analysis of 46 cases

目的分析22q11.2微缺失综合征(22q11.2 microdeletion syndrome,22q11.2DS)胎儿心脏超声特征及临床表型,以提高对22q11.2DS的认识。方法回顾性分析2013年1月至2019年4月于首都医科大学附属北京安贞医院胎儿心脏病母胎医学研究北京市重点实验室遗传数据库中有胎儿心脏超声检查及低覆盖度全基因组测序结果的先天性心脏畸形胎儿822例,从中选择46例测序结果为22q11.2DS胎儿为病例组,分析其表型、胎儿心脏超声特征及遗传学来源结果;再从中选择测序结果为阴性的68例圆锥动脉干畸形(conotruncal defects,CTD)胎儿为对照组,比较2组胎儿的心轴大小。采用独立样本t检验和χ2检验对数据进行统计学分析。结果822例中,46例胎儿22q11.2DS,其中遗传性22q11.2DS为23.3%(7/30)。CTD中22q11.DS检出率高于非CTD,分别为14.8%(45/305)和0.2%(1/517),χ2=74.253,P<0.001。病例组胎儿的心轴较对照组胎儿左偏[(61.7±15.3)°与(55.7±13.4)°,t=-3.843,P=0.001]。结论22q11.2DS表型以CTD常见,胎儿心脏超声提示CTD尤其同时合并心轴左偏时可疑诊22q11.2DS,并应行相应的产前遗传学检查确诊。

Objective To investigate the fetal echocardiographic features and clinical phenotype of 22q11.2 microdeletion syndrome(22q11.2DS)and provide information for the diagnosis of fetal 22q11.2DS.Methods We retrospectively retrieved information of 822 fetuses,who were diagnosed with congenital heart disease by fetal echocardiography,with results of low-coverage whole genome sequencing from the Genetic Database of Beijing Key Laboratory of Fetal Heart Disease and Maternal Fetal Medicine Research from January 2013 to April 2019.Phenotype,fetal echocardiographic features and genetic origin results of 46 fetuses with 22q11.2DS(22q11.2DS group)were summarized.Another 68 fetuses who were negative for 22q11.2DS but had conotruncal defects(CTD)were selected as control.Differences in fetal cardiac axis were compared between the two groups.Independent samples t test and Chi-square test were used for statistical analysis.Results 22q11.2DS was detected in 46 fetuses giving a total detection rate of 5.60%(46/822).The detection rates of 22q11.2DS in fetuses with CTD and non-CTD were 14.8%(45/305)and 0.2%(1/517),respectively(χ2=74.253,P<0.001).Fetal cardiac axis was left-deviated in those with 22q11.2DS compared with those of the control[(61.7±15.3)°vs(55.7±13.4)°,t=-3.843,P=0.001].Conclusions CTD are the common clinical phenotypes of fetal 22q11.2DS.Fetal 22q11.2DS should be considered and the corresponding prenatal genetic diagnosis is highly suggested when the fetus is diagnosed with CTD especially combined with an enlarged cardiac angle.