Diagnostic yield of exome sequencing in fetuses with renal malformations

Congenital malformations of the kidney and urinary tract (CAKUT) are relatively common with a prevalence of 4-60 in 10,000 livebirths and are the leading cause of all end stage pediatric kidney disease. Upon detection of CAKUT the question arises if further genetic testing is required. The purpose of this study was to determine the phenotypic presentation of CAKUT cases and the results of exome analysis (WES). This is a retrospective analysis of 63 out of 1123 fetal cases prenatally diagnosed with CAKUT at a single centre between August 2018 and December 2022. In fetuses with isolated CAKUT the overall rate of detecting a pathogenic variant in WES was five out of 40 (12.5%). Focusing on fetuses with isolated cystic kidney disease, the detection rate was 29% (4/14). In fetuses with extrarenal findings ten out of 23 fetuses (43.5%) were diagnosed with a pathogenic variant. WES provides an increase in diagnosing pathogenic variants in cases of prenatally detected CAKUT. Especially in fetuses with hyperechogenic and or polycystic kidney disease or with extrarenal malformations, WES facilitates a gain in information on the fetal genotype to enhance prenatal counselling and management.