本文报告了1例无创产前筛查(non-invasive prenatal screening, NIPS)假阴性的18-三体综合征病例.孕妇孕13周 +4超声检查示胎儿颈项透明层3.2 mm,NIPS结果为阴性,孕22周超声检查发现胎儿多发畸形,孕22周 +2再次行NIPS,结果依然为阴性.孕22周 +3终止妊娠.采用基于高通量测序技术的基因组拷贝数变异测序和荧光原位杂交检测引产后胎儿及附属物标本,结果显示胎儿组织(皮肤、肝脏)染色体结果为47,XY,+18;脐带根部、脐带中部染色体为47,XY,+18;胎盘胎儿面中心和近中心,以及胎盘母体面中心和近中心处均未检测到染色体异常;胎盘胎儿面边缘及母体面边缘检测结果分别为 Chr18:47,XY,+18/46,XY 和Chr18:47,XY,+18/46,XY.胎盘嵌合是导致本例NIPS假阴性的原因.提示,NIPS前、后的遗传咨询尤为重要;对于NIPS阴性者,后续的超声随访非常重要;胎儿出现与染色体异常关系密切的超声征象建议行有创产前诊断.
We hereby reported a case of false negative non-invasive prenatal screening(NIPS)for trisomy 18.The fetus with increased nuchal translucency(3.2 mm)detected by ultrasound scan at 13+4 gestational weeks received NIPS and the result was negative in chromosomes 21,18 and 13.A routine ultrasound examination at 22 weeks of gestation revealed multiple anomalies and a second NIPS was offered,which showed a negative result again.The pregnancy was terminated at 22+3 weeks.Multiple fetal and placental biopsies were collected for chromosome analysis using copy number variation sequencing based on high-throughput sequencing and fluorescence in situ hybridization.The fetal karyotype was shown to be 47,XY,+18 in fetal tissues(skin and liver)and umbilical cord,while no chromosomal abnormalities was detected at or near the center of the fetal and maternal surface of the placenta.Results of the chromosomal analysis along the edges of the fetal and maternal surfaces of the placenta were Chr18:47,XY,+18/46,XYand Chr18:47,XY,+18/46,XY,respectively.We inferred that placental mosaicism was the cause of the false negative NIPS result.Therefore,genetic counseling before and after NIPS is necessary.Follow-up ultrasound is important for NIPS-negative patients.Invasive prenatal diagnosis is recommended when abnormal ultrasound markers with possible genetic etiology were recognized.
Chinese Journal of Perinatal Medicine
Trisomy 18 syndrome
False negative reactions
Nuchal translucency measurement