Challenges in genetic counseling for congenital anomalies of the kidneys and urinary tract (CAKUT) spectrum

Abstract

Objectives: Congenital anomalies of the kidneys and urinary tract (CAKUT) are one of the most common sets of congenital defects. Bilateral renal agenesis is a severe presentation of the CAKUT spectrum. Case presentation: We report on two families who presented with recurrent pregnancies affected with bilateral renal agenesis and negative family histories. Likely pathogenic variants in the GREB1L gene were identified in the affected pregnancies and subsequently in their asymptomatic fathers. The first familial variant was identified by a multi-gene CAKUT panel and the second by whole exome sequencing. Renal ultrasound showed the father in family 1 had asymptomatic unilateral pelvic kidney and the father in family 2 had no apparent renal anomalies. Conclusions: Recent identification of genes responsible for CAKUT allows for genetic testing of affected families. Identification of the genetic etiology of CAKUT cases has multiple benefits including accurate risk assessment and reproductive options. Genetic counseling around CAKUT is challenging due to the extreme variability in presentation of the disorders.