胎儿超声微小异常的产前遗传学分析

目的探讨胎儿微小异常的产前超声表现及遗传咨询要点。 方法对2014年至2017年在北京协和医院经超声检查发现微小异常、核型分析正常但染色体微阵列分析显示拷贝数变异的胎儿17例，综合产前超声表现、遗传学检查结果、病理检查结果或出生后表现进行回顾分析。 结果超声检查显示不同种类和数目的微小异常，10例为单发异常，其余7例为多发异常。17例主要超声表现：测值小于孕周（7例）、脉络丛囊肿（2例）、心室强回声（1例）、肠管增宽或回声增强（4例）、肾盂增宽（2例）、侧脑室增宽（2例）、单脐动脉（2例）、永存右脐静脉（2例）、永存左上腔静脉（1例）、鼻骨缺失（4例）、手异常（3例）、足异常（1例）、羊水量异常（2例）及脐带异常（1例）。17例胎儿均进行了遗传学检查，核型分析及快速荧光原位杂交检测正常，通过染色体微阵列分析（CMA）检出不同片段大小的拷贝数变异，7例（41.18%）为致病性拷贝数变异，10例（58.82%）为意义不明的拷贝数变异（VOUS）。参考胎儿父母CMA诊断结果对10例VOUS进行了解释和区分，4例为偏致病性（VOUS-LP），3例为偏良性（VOUS-LB），3例意义不明确（VOUS-unknown）。经产前咨询后9例孕妇选择继续妊娠，胎儿出生后1例显示并趾及喂养困难，其余8例均生长发育正常；8例孕妇选择终止妊娠，其中2例引产胎儿行病理检查。 结论产前超声筛查未发现重大结构异常、但发现胎儿微小异常时应积极进行随诊，并行遗传学检查。与传统核型分析比较，CMA更有助于早期检出少见遗传学异常，为产前诊断和预后评估提供重要参考信息。

Prenatal genetic analysis of fetal minor abnormalities on ultrasound

ObjectiveTo investigate the sonographic diagnosis and genetic counseling of fetal minorabnormalities. MethodsCases of fetal minorabnormalities detected by prenatal ultrasound in our hospital were Peking union Medical College Hospital between 2014 and 2017 enrolled in this retrospective study. The results of ultrasonography, genetic testing, and pregnancy outcomes were analyzed. ResultsSeventeen fetuses with minorabnormalities were detected by ultrasound, among which 10 cases showed the isolated finding, 2 cases showed two findings, and 5 cases showed more than three findings. Abnormal ultrasound findings were as follows: fetal biometry small for gestational age in 7 cases, choroid plexus cysts in 2, echogenic intracardiac focus in 1, echogenic bowel in 4, pyelestasis in 2, mild ventriculomegaly in 2, single umbilical artery in 2, persistent right umbilical vein in 2, persistent left superior vena cava in 1, absent nasal bone in 4, hand anomalies in 3, foot anomaly in 1, abnormal amniotic fluid in 2, and umbilical cord abnormalities in 1. All cases underwent the genetic analysis including karyotype, fluorescent in situ hybridization (FISH), and chromosomal microarray analysis (CMA). All of them showed normal results in karyotype and FISH, but CMA identified different copy number variants (CNVs). Seven cases had pathogenic CNVs, and 10 cases had variants of uncertain significance (VOUS), including 4 with VOUS-likely pathogenic, 3 with VOUS-likely benign, and 3 with VOUS-unknown. After counseling 9 cases chose to continue the pregnancy and the remaining 8 cases chose to terminate the pregnancy. ConclusionsCareful examination and follow-up should be recommended in fetal minor abnormalitieson ultrasound. Prenatal genetic analysis could be recommended in such cases. Compared with traditional karyotyping, CMA could provide more information related with the prognosis of the fetuses, and prenatal counseling should be based on CMA results combined with ultrasound findings.