The correlations of prenatal renal ultrasound abnormalities with pathogenic CNVs in a large Chinese cohort.

Objective Our retrospective study aimed to assess the prenatal clinical utility of chromosome microarray (CMA) and the correlations of pathogenic copy number variants (CNVs) with different types of renal abnormalities detected by prenatal ultrasound screening and help to guide the optimal management for the relative late invasive diagnostic approach for renal abnormalities. Methods Fetus at 14-36 weeks of gestation were routinely screened for renal and other structural abnormalities at the Maternal and Child Health Hospital of Guangxi Autonomous Region. 877 fetuses with abnormal renal sonographic findings identified over a period of more than five years were subjected for CMA analysis using materials obtained from chorionic villi sampling, amniocentesis or cordocentesis. Results Renal abnormal cases that were subjected for CMA test constituted 2.44% (877/35,884) of all ultrasound abnormal fetus that were tested by CMA in this single center. The anomalies were diagnosed rather late in this series as 64% of isolated renal anomalies performed cordocentesis rather than CVSs. Ten types of overlapping renal anomalies were reported by prenatal ultrasound screening. Fetal pyelectasis was the most common renal ultrasound finding, it accounted for a third (34.32%, 301/877) of all fetuses with renal anomalies but only 3.65% (isolated case: 2.36% (4/169) and non-isolated case: 5.30% (7/132)) of them harbored pathogenic CNV. Hyperechogenic kidneys accounted for 5.47% of fetuses with renal anomalies, 39.58% (isolated case: 44.44% (16/36) and non-isolated case: 25.00% (3/12)) had pathogenic CNV findings, the highest diagnostic yield among all groups. Renal agenesis which accounted for 9.92% of all abnormal renal cases had a CMA diagnostic yield of 12.64% (isolated case: 11.53% (9/78) and non-isolated case: 22.22% (2/9), unilateral case:11.39% (9/79) and bilateral case: 25.0% (2/8)), whereas multicystic dysplastic kidney (n=110), renal cyst (n=34), renal dysplasia (n=27), crossed fused renal ectopia (n=31), hydronephrosis (n=98), renal duplication (n=42) and ectopic kidney (n=99) had an overall diagnostic rate of 11.81%, 11.76%, 7.40%, 6.45%, 6.12% , 4.76% and 3.03% respectively. The live-and-well infant rate was significantly higher in CMA negative fetuses with isolated fetal pyelectasis and ectopic kidney whereas the rate was significantly lower in fetuses with isolated renal agenesis, multicystic dysplastic kidney and sever hydronephrosis. The most common pathogenic CNV was 17q12 deletion (n=22), which accounted for 30.13% (22/73) of all positive CMA findings with a rate of 2.50% (22/877) among fetus with all abnormal renal findings. Fetuses with 17q12 deletion exhibited a wide range of renal phenotypes. Other recurrent CNVs associated with prenatal renal ultrasound abnormalities were 22q11.2, Xp21.1, Xp22.31, 2q13, 16p11.2, 1q21 which collectively accounted for 2.16% (19/877) of the fetuses with prenatal renal anomalies. Conclusion We retrospectively reviewed the CMA findings for a large cohort of fetus with different types of renal ultrasound abnormalities. The CNV detection rate varied significantly (3.03%-39.58%) among groups. The most consistent ultrasound indication for CMA test would be hyperechogenic kidney. Our data provided specific guidance for ordering prenatal genetic testing for fetus with renal ultrasound findings. Specifically it is more appropriate to perform CMA test for isolated fetal pyelectasis postnatally rather than prenatally via cordocentesis at the third trimester. This article is protected by copyright. All rights reserved.