106例胎儿颈项透明层增厚的超声与遗传学产前诊断结果对照分析

A comparative study of ultrasound and genetic prenatal diagnosis in 106 NT-thickened fetuses

目的:探讨产前超声提示胎儿颈项透明层(nuchal translucency,NT)增厚的临床价值,并对比遗传学产前诊断结果。方法:对106例胎儿NT增厚的超声与遗传学产前诊断结果进行对比分析(所有胎儿均行染色体微阵列分析,其中有4例进行了全外显子测序,1例行SMN1基因检测),并跟踪妊娠结局。结果:共发现44例(41.51%)遗传学异常,2例临床意义不明性拷贝数变异。遗传学异常中共包含39例染色体异常(34例非整倍体异常和5例为致病性拷贝数变异)及5例基因异常(均为致病性或可能致病性变异)。随着NT厚度的增加,遗传学异常的发生率明显升高。44例遗传学异常胎儿中有38例(86.36%)合并其他超声异常,其中鼻骨发育不良占比最高。结论:发现胎儿NT增厚应首先考虑染色体异常尤其是非整倍体异常。NT增厚还与拷贝数变异及某些单基因遗传病有关。对于染色体微阵列阴性的NT增厚胎儿,可结合超声及家族史等综合考虑行全外显子检测。

Objective:To explore the clinical value of prenatal ultrasound in suggesting thickening of the nuchal translucency(NT)in fetuses and to compare it with the results of genetic prenatal diagnosis.Methods:The results of ultrasound and genetic prenatal diagnosis of 106 fetuses with thickening of the NT were compared and analyzed(all fetuses were subjected to chromosomal microarray analysis,with whole-exome sequencing in four cases and SMN1 gene testing in one case),and pregnancy outcomes were followed.Results:A total of 44 cases(41.51%)of genetic abnormalities and 2 cases of copy number variants of unknown clinical significance were identified.These genetic abnormalities included 39 cases of chromosomal abnormalities(34 cases of aneuploidy abnormalities and 5 cases of pathogenic copy number variants)and 5 cases of genetic abnormalities(all pathogenic or suspected pathogenic variants).The incidence of genetic abnormalities increased significantly with increasing thickness of the NT.In addition,38(86.36%)of 44 fetuses with genetic abnormalities were combined with other ultrasound abnormalities,with the highest percentage of nasal bone dysplasia.Conclusion:When thickened NT is detected in fetuses,chromosomal abnormalities,especially aneuploidy,should be considered first.The thickened NT is also associated with copy number variations and certain monogenic inherited diseases.For fetuses with thickened NT and negative chromosome microarray analysis,comprehensive consideration including ultrasound and family history may warrant the whole-exome sequencing.