Genetics of human congenital urinary bladder disease

Lower urinary tract and/or kidney malformations are collectively the most common cause of end-stage renal disease in children, and they are also likely to account for a major subset of young adults requiring renal replacement therapy. Advances have been made regarding the discovery of the genetic causes of human kidney malformations. Indeed, testing for mutations of key nephrogenesis genes is now feasible for patients seen in nephrology clinics. Unfortunately, less is known about defined genetic bases of human lower urinary tract anomalies. The focus of this review is the genetic bases of congenital structural and functional disorders of the urinary bladder. Three are highlighted. First, prune belly syndrome, where mutations of CHRM3, encoding an acetylcholine receptor, HNF1B, encoding a transcription factor, and ACTA2, encoding a cytoskeletal protein, have been reported. Second, the urofacial syndrome, where mutations of LRIG2 and HPSE2, encoding proteins localised in nerves invading the fetal bladder, have been defined. Finally, we review emerging evidence that bladder exstrophy may have genetic bases, including variants in the TP63 promoter. These genetic discoveries provide a new perspective on a group of otherwise poorly understood diseases.