Prenatal genetic analysis of fetal minor abnormalities on ultrasound

Abstract

Objective To investigate the sonographic diagnosis and genetic counseling of fetal minorabnormalities. Methods Cases 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. Results Seventeen 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. Conclusions Careful 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. Key words: Ultrasonography; Genetic analysis; Chromosomal microarray analysis; Copy number variants