The biology of congenital urinary bladder outflow obstruction

Congenital urinary bladder outflow obstruction (BOO) is a major cause of kidney failure in children. Sometimes, it is caused by anatomical obstruction of the urethra. In other cases, functional failure of voiding occurs without anatomical obstruction. Bladder development is driven by genes expressed in smooth muscle, neural and urothelial cell lineages. Variants in the coding regions of such genes cause a subset of BOO. In other cases, such as posterior urethral valves (PUV), noncoding variants may influence susceptibility. By modelling BOO in mutant mice, combined with viral vector mediated gene therapy, steps are being made to ameliorate the pathobiology of these diseases. Translation of such strategies to humans may require prenatal gene therapy.