早孕期胎儿肢体畸形2例的超声及遗传学诊断

Ultrasound and genetic diagnosis of 2 cases of fetal limb malformation in early pregnancy

目的本研究报道2例早孕期海豹肢畸形胎儿NT超声表现及产前基因诊断。方法纳入2020年12月、2021年8月于甘肃省妇幼保健院产前诊断中心就诊经NT超声诊断海豹肢畸形2例,总结其超声声像图及畸形特征,并行染色体核型检查及CNV-seq检测进行遗传学诊断。结果此2例病例均来自同一孕妇,病例1经NT超声诊断后行引产处理,引产1死胎,结合产前超声显示、尸检外观,能够证实该畸形儿为双上肢完全型海豹肢、双下肢完全型海豹肢。胎儿染色体核型检查及CNV-seq检测结果显示(X)(p22.33q28)del 155.27 Mb,为X染色体单体,也称特纳综合征(Turnersyndrome),流产组织染色体检查结果与绒穿结果相符,染色体核型分析结果为45,X0[10%]/46,XN[90%]嵌合体。此孕妇半年后再次自然受孕胎儿仍为完全性海豹肢、全身皮肤水肿并颈部水囊瘤。经超声诊断后行引产处理,流产组织WES发现父源性SLC26A2 c.870delG、母源性SLC26A2 c.1020-c.1022delTGT可能致病性基因变异(分级为LP)。结论NT超声运用连续顺序追踪超声法,可在孕中早期明确诊断“海豹肢”畸形,有助于临床早期评判预后。

Objective This study reported the NT ultrasound findings and prenatal gene diagnosis of 2 fetuses with seal limb malformation in early pregnancy.Methods Two cases of seal limb malformation diagnosed by NT ultrasound were included in the prenatal diagnosis center of Gansu Provincial Maternal and Child Health Care Hospital in December 2020 and August 2021,and their ultrasonic images and malformation characteristics were summarized,and genetic diagnosis was performed by chromosome karyotype examination and CNV-seq detection.Results The two cases were from the same pregnant woman.Case 1 underwent labor induction after NT ultrasound diagnosis,and labor induction was a stillbirth.Combined with prenatal ultrasonography and autopsy appearance,it was confirmed that the deformed child was a complete seal limb with two upper limbs and a complete seal limb with two lower limbs.The results of fetal chromosome karyotype examination and CNV-seq test showed that(X)(p22.33q28)del 155.27 Mb was a monomer of X chromosome,also known as Turner syndrome.The results of chromosome examination in aborted tissue were consistent with the results of fleecing.Karyotype analysis showed 45,X0[10%]/46,XN[90%]chimeras.The fetus was naturally conceived again six months later and still had complete seal limbs,skin edema and neck hygroma.After ultrasound diagnosis and labor induction treatment,the abortion tissue WES found paternal SLC26A2 c.870delG and maternal SLC26A2 c.1020-c.1022delTGT pathogenic gene variation(LP grade).Conclusion NT ultrasound using continuous sequential tracking ultrasound can clearly diagnose the“seal limb”deformity in early pregnancy,which is helpful to evaluate the prognosis in early clinical stage.