Familial vesicoureteral reflux: Influence of sex on prevalence and expression

Purpose: Familial clustering of vesicoureteral reflux implies that genetic factors have an important role in the pathogenesis of vesicoureteral reflux. We investigated the impact of sex on familial vesicoureteral reflux. Materials and Methods: Between 1998 and 2003 we identified 159 white families with at least 2 children (range 2 to 5) with vesicoureteral reflux confirmed by a voiding cystourethrogram. Families were divided into 3 groups, including group 1 with only boys affected (29 or 18%), group 2 with only girls affected (57 or 36%) and group 3 with boys and girls affected (73 or 46%). Clinical characteristics, reflux grade and associated renal anomalies in these 3 groups were compared using the MannWhitney U and chi-square tests for statistical analysis. Results: Sisters of index female patients were at significantly higher risk for vesicoureteral reflux than brothers (p < 0.01). Boys in group 1 had a significantly higher grade of vesicoureteral reflux than boys in group 3, and girls in groups 3 and 2 (p = 0.018, < 0.001 and < 0.0001, respectively). Severe renal scarring was present in 7% of boys in group 1, 6.6% of boys in group 3, 1.3% of girls in group 3 and 1.9% of girls in group 2. Duplex kidneys were present in 15.3% of boys in group 1 but only in 2.3% of boys in group 3 (p < 0.01), 5.7% of girls in group 3 and 5.8% of girls in group 2. Age at diagnosis was not significantly different among boys in groups I and 3, and girls in group 2 (median 0.9, 0.6 and 1.9 years, respectively). Conclusions: The risk and severity of vesicoureteral reflux in siblings depends on the sex of the affected child. Brothers of index male patients have higher grade of reflux and higher rate of associated duplex systems. This has implications for genetic counseling and for modeling the inheritance of vesicoureteral reflux.