Prenatal diagnosis of polycystic renal diseases: diagnostic yield, novel disease-causing variants, and genotype–phenotype correlations

Abstract

BackgroundPolycystic renal disease (PRD) is a frequent congenital anomaly of the kidneys, but research utilizing chromosomal microarray analysis (CMA) and exome sequencing (ES) in PRD fetuses remains sparse, with the majority of studies focusing on the multisystem or genitourinary system. ObjectiveThis study aims to describe the detection rate of detectable genetic causes of fetal PRD at different levels, and novel disease-causing variants and explores genotype-phenotype correlations. Study DesignThis study included 220 fetal PRD from January 2014 to June 2022. Cases were divided into three groups: isolated multicystic dysplastic kidneys (MCDK), non-isolated MCDK, and suspected polycystic kidney disease group. We reviewed data on maternal demographics, ultrasonographic results, CMA/ES results, and pregnancy outcomes. ResultsIn our cohort, CMA identified 19 (8.6%) fetuses carrying chromosomal abnormalities, and the most common CNV was 17q12 microdeletion (7/220, 3.2%). Furthermore, 94 families chose to perform trio-ES testing, and 21 fetuses (22.3%) were found to harbor P/LP variants. For PRD, there was a significant difference in the live birth rate (91/130 vs. 46/80 vs. 1/10, p < 0.001). Among 138 live birth cases, 106 (78.5%) underwent postnatal ultrasound review, of which 95 (89.6%) had a consistent prenatal-postnatal ultrasound diagnosis. ConclusionsTaken together, either for isolated or non-isolated PRD, our data show high detection efficiency for both testing tools. Novel pathogenic variants have expanded the disease spectrum of PRD-associated genes while enriching the genotype-phenotype correlation. Therefore, we consider it feasible to perform CMA + ES testing in fetal PRD. Moreover, prenatal-postnatal ultrasound concordance was greater, while the live birth rate was higher and prognosis was better when known genetic disorders were excluded, showing that genetic testing results significantly influenced pregnancy decisions.