26例胎儿鼻骨发育异常的产前诊断结果分析

目的探讨胎儿鼻骨缺失和发育不良的产前诊断、遗传咨询、临床处理路径。方法2016年12月1日至2017年12月1日,在中国医学科学院北京协和医院产检的孕妇中,发现鼻骨发育异常26例,根据是否合并其他超声异常,分为孤立性和非孤立性鼻骨发育异常两组。所有病例均行产前染色体核型分析及染色体微阵列分析(chromosomal microarray analysis,CMA),回顾性分析两组病例的临床资料、产前遗传学诊断结果和妊娠结局。结果孤立性鼻骨缺失或发育不良共18例,其中14例染色体核型分析及CMA结果未见异常,另4例CMA结果为临床意义不明的拷贝数变异(variants of unknown significance,VUS),偏良性,均继续妊娠,随访新生儿均正常。非孤立性鼻骨缺失或发育不良共8例,1例为21三体,2例为18三体,2例CMA结果为致病性拷贝数变异(copy number variation,CNV)。3例染色体核型分析和CMA均未见异常,其中1例进一步行全外显子测序(whole exome sequencing,WES)分析,提示胎儿为RPGRIP1L基因的复合杂合突变,诊断为Meckel综合征。8例非孤立性鼻骨缺失或发育不良的病例中,7例孕妇选择终止妊娠,另1例双胎之一超声异常,畸形新生儿出生后即夭折。结论对于产前超声发现鼻骨发育异常的病例,无论其是否合并其他超声异常,均建议行包括CMA在内的产前遗传学诊断,必要时进一步行WES分析。

Analysis of prenatal diagnostic results in fetuses with nasal bone abnormalities of 26 cases

Objective To investigate the prenatal diagnosis,genetic counseling and clinical management pathway of fetal nasal bone absence or hypoplasia.Methods This retrospective study included 26 cases with fetal nasal bone absence or hypoplasia detected by prenatal ultrasonography from December 1st,2016 to December,1st 2017 in Department of Obstetrics&Gynecology,Peking Union Medical College Hospital.Cases combined with or without other ultrasonographic abnormalities were divided into non-isolated and isolated nasal bone absence or hypoplasia group respectively.Karyotyping and chromosomal microarray analysis(CMA)were performed in all cases.The clinical profiles,prenatal genetic diagnostic results and pregnancy outcomes of two groups were analyzed retrospectively.Results Among 18 cases in isolated nasal bone absence or hypoplasia group,4 patients had variants of unknown significance(VUS)results,all were likely benign.The remaining 14 cases had normal genetic results.All these 18 cases continued the pregnancies and all the infants were normal in follow-up.Among 8 cases in nonisolated nasal bone absence or hypoplasia group,one fetus was diagnosed as trisomy 21,two fetuses were diagnosed as trisomy 18.Two fetuses were identified with pathological copy number variant(CNV).No abnormal genetic diagnoses were found after karyotyping and CMA in the remaining 3 cases,further whole exome sequencings performed in 1 case revealed a compound heterogenous mutation in RPGRIP1L gene.Seven cases opted to terminate pregnancies after genetic counseling.In addition,one fetus with multiple structural abnormalities in a twin,the malformed newborn died after delivery.Conclusions Prenatal genetic diagnostic testing,including CMA,should be performed in any case with nasal bone abnormalities,whether it is combined with other ultrasonographic abnormalities or not.Further WES should be applied if necessary.