Etiology and outcomes of fetal renal abnormalities in Southern China: a single-tertiary-center study

TL;DR

This study explores the causes and outcomes of fetal kidney abnormalities in Southern China, finding that certain kidney conditions are linked to genetic mutations.

Contribution

The study expands the understanding of fetal renal abnormalities' etiology and confirms the clinical value of whole-exome sequencing in prenatal screening.

Findings

Pathogenic copy-number variations were detected in 8.6% of cases, with abnormalities in 22q11.2 or 17q12 being most common.

Hyperechogenic kidney was associated with the highest rate of pathogenic variation (19.8%), while hydronephrosis had the lowest.

Abstract

Although renal abnormalities are common during fetal growth, the etiology remains largely unclear. This study aimed to determine the outcomes of fetuses with renal anomalies and the corresponding etiologies. We retrospectively analyzed data from 1,019 cases for which chromosomal microarray analysis (CMA) was performed; 58 CMA-negative fetuses were selected for whole-exome sequencing (WES).

Pathogenic copy-number variations were detected in 88 (8.6%) cases, comprising 25 aneuploidies, 10 macrodeletions/macroduplications, and 53 microdeletions/microduplications. Among the latter, abnormalities in the 22q11.2 or 17q12 region were the most common, followed by those in the 16p11.2 region. Of the 58 CMA-negative samples, six showed abnormal WES results. The genes with pathogenic variants were KMT2D, PKD1, BBS1, NPHP3, BBS2, and HNF1B. Hyperechogenic kidney was associated with the highest rate of pathogenic variation (19.8%), followed by renal dysplasia (18.8%). In contrast, hydronephrosis and horseshoe kidney were associated with the lowest incidence of pathogenic variants. The 871 cases with successful follow-up (85.5%) included 120 terminations, 2 stillbirths, and 4 perinatal deaths. Of the remaining 745 live births with renal abnormalities, 63 underwent surgery, and 3 presented with developmental delay. Surgery was most commonly performed in newborns with hydronephrosis (26.8%).

The prenatal ultrasound-screening of fetal renal abnormalities, whether isolated or non-isolated, should be accompanied by rapid etiological analysis. In particular, we noted a high incidence of pathogenic variants in fetal hyperechogenic kidneys, while hydronephrosis was associated with few pathogenic variants and good prognosis after birth.

The etiology of fetal renal abnormalities remains unclear for many patients. In this study, we investigated the underlying causes, clinical phenotypes, and outcomes. We performed whole-exome sequencing on 1,019 specimens from fetuses with ultrasound-verified renal abnormalities. Our single-tertiary-center study expands on the etiology of renal abnormalities and confirms the clinical utility of whole-exome sequencing for prenatal screening.

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