Genetics of anomalies of the kidney and urinary tract with congenital heart disease: A review

Congenital anomalies of the kidney and urinary tract (CAKUT) and congenital heart disease (CHD) are the most common congenital defects and constitute a major cause of morbidity in children. Anomalies of both systems may be isolated or associated with congenital anomalies of other organ systems. Various reports support the co-occurrence of CAKUT and CHD, although the prevalence can vary. Cardiovascular anomalies occur in 11.2% to 34% of patients with CAKUT, and CAKUT occur in 5.3% to 35.8% of those with CHD. The co-occurrence of genetic factors in both CAKUT and CHD would raise common etiologies including genetics, genetic-environmental interactions, or shared molecular mechanisms and pathways such as NODAL, NOTCH, BMP, WNT, and VEGF. Studies in animal models and humans have indicated a genetic etiology for CHD and CAKUT with hundreds of genes recognized and thousands of entries, found in a catalog of human genetic disorders. There are over 80 CAKUT genes and over 100 CHD genes available for clinical testing. For example, the HNFIB gene accounts for 5% to 31% of reported cases of CAKUT. In view of the association between CAKUT and CHD, a thorough cardiac examination should be performed in patients with CAKUT, and a similar evaluation for CAKUT in the presence of CHD. This will allow early diagnosis and therapeutic intervention to improve the long- term outcome of patients affected, and test for at-risk family members. We present here evidence for an association of anomalies involving the two organ systems, and discuss possible etiologies of targeted genes, their functions, biological processes and interactions on embryogenesis. Anomalies of the kidney and heart are the most commonly recognized congenital defects and constitute a major cause of morbidity in children. For example, STRING protein-protein interaction network for the hepatocyte nuclear factor 1-beta (HNF1B) gene with first-tier functional interactions involving detection of glucose and exocrine pancreas development with DNA and chromatin binding properties impacting transcription activity shows 10 nodes with 35 edges as illustrated affects development the kidney and urinary tract system. Network nodes represent proteins with splice isoforms or post-translational modifications collapsed into each node for all proteins produced by a single protein-coding gene. Edges represent protein-protein associations that are considered specific and meaningful, that is, proteins jointly contribute to a shared function. The HNF1B gene is the most known common cause of kidney and urinary tract defects accounting for 5%-31% of reported cases. image