Novel genetic aspects of congenital anomalies of kidney and urinary tract

Abstract

Purpose of review: Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most frequent organ malformations. They are a relevant cause of chronic renal failure in children. Apart from isolated forms of CAKUT, more than 500 syndromes have been described that are characterized by combined defects of the kidney and other organ systems. Familial aggregation of renal malformations in approximately 10% of patients suggests that genetic events might be involved. Modifying effects due to missense mutations in additional developmental genes seem to enhance the phenotypic variability in affected families. In these families, genetic counseling can be difficult. In contrast, in patients with defined autosomal dominant disease, genetic counseling is of high clinical relevance, also with respect to additional extrarenal symptoms.

Recent findings: Due to the development of numerous genetic knock-out mouse models, the identification of specific renal developmental genes and the application of novel sequencing techniques of the human genome, our understanding of kidney organogenesis has largely improved during very recent years.

Summary: This review will focus on important genetic factors that influence nephrogenesis and highlight important human disorders that are associated with anomalies of kidneys, proximal and distal urinary tract.