Hereditary Vesicoureteral Reflux: A Study of 66 Families


Purpose: We studied the inheritance pattern, clinical features and outcome in children with vesicoureteral reflux (VUR). Characteristics of known familial VUR cases were also compared with those of sporadic VUR. Material and Methods: 726 patients were treated for VUR between 1990-2004. The families were contacted by letter inquiring if other members of the family were affected. The phenotype of all cases (familial and non-familial) was characterized in terms of presenting symptoms, reflux grade, recurrent urinary tract infections, kidney damage, and the natural course of reflux. Results: The response rate was 79%. A total of 99 individuals (22%) reported relatives with VUR. Since some of the 99 index cases belonged to the same family, the total number of families was ultimately 66. The distribution of relatives with VUR was: 38 siblings, 20 parents (15 mothers), 19 cousins, 15 aunts/uncles and 12 grandparents. The phenotype of VUR did not differ between familial and non-familial cases. However, VUR among relatives was of milder grade than index and sporadic cases. Conclusions: The proportion of hereditary reflux in our material was lower than in other studies (22%). We found a strong overrepresentation of maternal transmission of reflux. Severity of the disease did not differ between familial and non-familial VUR.

Share and Cite:

Bartik, Z. , Nordenskjöld, A. , Sjöström, S. , Sixt, R. and Sillén, U. (2015) Hereditary Vesicoureteral Reflux: A Study of 66 Families. Open Journal of Pediatrics, 5, 304-313. doi: 10.4236/ojped.2015.54046.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Amar, A.D. (1972) Familial Vesicoureteral Reflux. The Journal of Urology, 108, 969-971.
[2] Jerkins, G.R. and Noe, H.N. (1982) Familial Vesicoureteral Reflux: A Prospective Study. The Journal of Urology, 128, 774-778.
[3] Parekh, D.J., Pope, J.C.T., Adams, M.C. and Brock 3rd., J.W. (2002) Outcome of Sibling Vesicoureteral Reflux. The Journal of Urology, 167, 283-284.
[4] Wan, J., Greenfield, S.P., Ng, M., Zerin, M., Ritchey, M.L. and Bloom, D. (1996) Sibling Reflux: A Dual Center Retrospective Study. The Journal of Urology, 156, 677-679.
[5] Kaefer, M., Curran, M., Treves, S.T., Bauer, S., Hendren, W.H., Peters, C.A., Atala, A., Diamond, D. and Retik, A. (2000) Sibling Vesicoureteral Reflux in Multiple Gestation Births. Pediatrics, 105, 800-804.
[6] Noe, H.N., Wyatt, R.J., Peeden Jr., J.N. and Rivas, M.L. (1992) The transmission of Vesicoureteral Reflux from Parent to Child. The Journal of Urology, 148, 1869-1871.
[7] Sjostrom, S., Sillen, U., Jodal, U., Sameby, L., Sixt, R. and Stokland, E. (2010) Predictive Factors for Resolution of Congenital High Grade Vesicoureteral Reflux in Infants: Results of Univariate and Multivariate Analyses. The Journal of Urology, 183, 1177-1184.
[8] Zu, S., Bartik, Z., Zhao, S., Sillen, U. and Nordenskjold, A. (2009) Mutations in the ROBO2 and SLIT2 Genes Are Rare Causes of Familial Vesico-Ureteral Reflux. Pediatric Nephrology, 24, 1501-1508.
[9] Lebowitz, R.L., Olbing, H., Parkkulainen, K.V., Smellie, J.M. and Tamminen-Mobius, T.E. (1985) International System of Radiographic Grading of Vesicoureteric Reflux. International Reflux Study in Children. Pediatric Radiology, 15, 105-109.
[10] Schwartz, G.J., Brion, L.P. and Spitzer, A. (1987) The Use of pLasma Creatinine Concentration for Estimating Glomerular Filtration Rate in Infants, Children, and Adolescents. Pediatric Clinics of North America, 34, 571-590.
[11] Brochner-Mortensen, J., Haahr, J. and Christoffersen, J. (1974) A Simple Method for Accurate Assessment of the Glomerular Filtration Rate in Children. Scandinavian Journal of Clinical and Laboratory Investigation, 33, 140-143.
[12] Winberg, J. (1959) The 24-Hour True Endogenous Creatinine Clearance in Infants and Children without Renal Disease. Acta Paediatrica, 48, 443-452.
[13] Conte, M.L., Bertoli-Avella, A.M., de Graaf, B.M., Punzo, F., Lama, G., La Manna, A., Grassia, C., Rambaldi, P.F., Oostra, B.A. and Perrotta, S. (2008) A Genome Search for Primary Vesicoureteral Reflux Shows Further Evidence for Genetic Heterogeneity. Pediatric Nephrology, 23, 587-595.
[14] Feather, S.A., Malcolm, S., Woolf, A.S., Wright, V., Blaydon, D., Reid, C.J., Flinter, F.A., Proesmans, W., Devriendt, K., Carter, J., Warwicker, P., Goodship, T.H. and Goodship, J.A. (2000) Primary, Nonsyndromic Vesicoureteric Reflux and Its Nephropathy Is Genetically Heterogeneous, with a Locus on Chromosome 1. American Journal of Human Genetics, 66, 1420-1425.
[15] Scott, J.E., Swallow, V., Coulthard, M.G., Lambert, H.J. and Lee, R.E. (1997) Screening of Newborn Babies for Familial Ureteric Reflux. Lancet, 350, 396-400.
[16] Naseri, M., Ghiggeri, G.M., Caridi, G. and Abbaszadegan, M.R. (2010) Five Cases of Severe Vesico-Ureteric Reflux in a Family with an X-Linked Compatible Trait. Pediatric Nephrology, 25, 349-352.
[17] Marchini, G.S., Onal, B., Guo, C.Y., Rowe, C.K., Kunkel, L., Bauer, S.B., Retik, A.B. and Nguyen, H.T. (2012) Genome Gender Diversity in Affected Sib-Pairs with Familial Vesico-Ureteric Reflux Identified by Single Nucleotide Polymorphism Linkage Analysis. BJU International, 109, 1709-1714.
[18] Esbjorner, E., Hansson, S. and Jakobsson, B. (2004) Management of Children with Dilating Vesico-Ureteric Reflux in Sweden. Acta Paediatrica, 93, 37-42.
[19] Sjostrom, S., Sillen, U., Bachelard, M., Hansson, S. and Stokland, E. (2004) Spontaneous Resolution of High Grade Infantile Vesicoureteral Reflux. The Journal of Urology, 172, 694-699.
[20] Menezes, M. and Puri, P. (2009) Familial Vesicoureteral Reflux—Is Screening Beneficial? The Journal of Urology, 182, 1673-1677.
[21] Noe, H.N. (1992) The Long-Term Results of Prospective Sibling Reflux Screening. The Journal of Urology, 148, 1739-1742.
[22] Brandstrom, P., Esbjorner, E., Herthelius, M., Holmdahl, G., Lackgren, G., Neveus, T., Sillen, U., Sixt, R., Sjoberg, I., Stokland, E., Jodal, U. and Hansson, S. (2010) The Swedish Reflux Trial in Children: I. Study Design and Study Population Characteristics. The Journal of Urology, 184, 274-279.
[23] Cascio, S., Yoneda, A., Chertin, B., Colhoun, E. and Puri, P. (2003) Renal Parenchymal Damage in Sibling Vesicoureteric Reflux. Acta Paediatrica, 92, 17-20.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.