UNRAVELING THE GENETICS OF VESICOURETERAL REFLUX - A COMMON FAMILIAL DISORDER

Primary vesicoureteric reflux (VUR) is one of the more common genetic disorders. Little is yet known about the genetics of this potentially manageable childhood condition, which is characterised by regurgitatio n of urine from the bladder to the kidney, The VUR phenotype is associ ated with shortness of the submucosal segment of the ureter due to con genital lateral ectopia of the ureteric orifice. VUR is found in 30-50 % of infants and young children with a urinary tract infection, A seri ous concern in families with an affected patient is that approximately one half df siblings or offspring will be affected, but up to a half of these affected siblings and offspring may be asymptomatic in childh ood. If left untreated, these patients may present later in life with proteinuria, hypertension or renal failure, VUR is the commonest cause of end-stage renal failure in children, and an important cause in adu lts. As the kidney damage resulting from severe VUR is preventable, ea rly detection is desirable. The techniques for clinical diagnosis are invasive and costly, reinforcing the importance of identification of a gene for VUR to facilitate genetic screening. Although family studies suggest a major dominant gene, the inheritance pattern is still a mat ter of debate. In rare instances, VUR occurs in association with other diseases, such as the coloboma-ureteric-renal syndrome, which is caus ed by a PAX2 gene mutation. In this review, we present evidence that t his common disorder may be caused by mutations in the developmental pa thway of which the PAX2 gene forms a part.