Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects and the leading cause of end-stage renal disease in children. There is a wide spectrum of renal abnormalities, from mild hydronephrosis to more severe cases, such as bilateral renal dysplasia. The etiology of the majority of cases of CAKUT remains unknown, but there is increasing evidence that genomic imbalance contributes to the pathogenesis of CAKUT. Advances in human and mouse genetics have contributed to increased understanding of the pathophysiology of CAKUT. Mutations in genes involved in both transcription factors and signal transduction pathways involved in renal development are associated with CAKUT. Large cohort studies suggest that copy number variants, genomic, or de novo mutations may explain up to one-third of all cases of CAKUT. One of the major challenges to the use of genetic information in the clinical setting remains the lack of strict genotype-phenotype correlation. However, identifying genetic causes of CAKUT may lead to improved diagnosis of extrarenal complications. With the advent of decreasing costs for whole genome and exome sequencing, future studies focused on genotype-phenotype correlations, gene modifiers, and animal models of gene mutations will be needed to translate genetic advances into improved clinical care.
Keywords: CAKUT; congenital anomalies of kidney; genetics; renal development.