Genetic Investigation of Pregnancies With an Isolated Fetal Pelvic Kidney

ABSTRACT Objective To explore genetic investigative results in fetuses with isolated pelvic kidney. Methods This was a retrospective study of 212 fetuses with isolated pelvic kidney diagnosed on second trimester anatomy ultrasound. All cases underwent invasive prenatal diagnosis for copy number variant (CNV) detection by chromosomal microarray analysis (CMA). For those with a negative CNV, trio exome sequencing (ES) was an option. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, molecular testing results, and pregnancy outcomes. Results In total, 212 cases underwent CMA testing, which identified one case of pathogenic CNV, specifically a de novo 16p11.2 microdeletion. Among the cases that yielded negative results from CMA, 118 proceeded to trio ES. Five (4.2%; 5/118) disease‐causing variants across five unrelated fetuses, involving four genes: DLL1 , KMT2D , PTEN and PRKG1 , with two cases harboring distinct pathogenic variants in KMT2D . Following rigorous phenotype–genotype correlation assessment, only the two KMT2D variants were deemed clinically attributable, resulting in an attributable diagnostic yield of 1.7% (2/118). The remaining three variants were classified as incidental findings. With the exception of the PRKG1 variant, which was inherited from the mother, the remaining four variants were confirmed as de novo. Conclusion Our results should raise clinical awareness among obstetricians and maternal‐fetal medicine specialists regarding the potential syndromic associations of pelvic kidney.