Clinical polymorphism and genetic characteristic of Denys-Drash and Frasier syndromes

The Denys-Drash and Frasier syndrome are primary genetic diseases with an early debut of the nephrotic syndrome in children with male pseudohermaphroditism and a mutation in gene WT1 (a gene of Wilms’tumour). A half of patients with the Denys-Drash syndrome has a Wilms tumour. All patients develop chronic renal failure. The therapy of nephrotic syndrome should eliminate steroid and cytostatic therapy. Polymorphism of clinical features and the genetic characteristic of the Denys-Drash and Frasier syndromes is presented, criteria of diagnostics and optimal tactic of treatment are offered.

нефротический синдром, гормонорезистентный мужской псевдогермафродитизм, дисгенезия гонад, 11-я хромосома, WT1, 46,XY, синдром Дениса-Драша, синдром Фрайзера

1. Игнатова М.С., Курбанова Э.Г. Нефротический синдром при гломерулонефрите. В кн.: Иммуносупрессивная терапия нефротического синдрома у детей. М.: Novartis, 2000: 10-11.

2. Armstrong J.F., Pritchard-Jones K., Bickmore W.A., Hastie N.D., Bard J.B. The expression of the Wilms’ tumour gene, WT1, in the developing mammalian embryo. Mech Dev 1992; 40: 85-97.

3. Bain A.D., Scott J.S. Mixed gonadal dysgenesis with XX/XY mosaicism. Lancet 1965; 1: 1035-1038.

4. Bardeesy N., Zabel B., Schmitt K., Pelletier J. WT1 mutations associated with incomplete Denys-Drash syndrome define a domain predicted to behave in a dominant-negative fashion brief report. Genomics 1994; 21: 663-665.

5. Beckwith J.B., Kiviat N.B., Bonadio J.F. Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms’ tumor. Pediatr Pathol 1990; 10: 1-36.

6. Breslow N., Beckwith J., Ciol M., Sharples K. Age distribution of Wilms’ tumour: report from the national Wilms’ tumour study group. Cancer Res 1988; 48: 1653-1657.

7. Coppes M.J., DeKraker J., van Dijken P.J. et al. Bilateral Wilms’ tumour: long term survival and some epidemiological features. J Clin Oncol 1989; 7: 310-315.

8. Denys P., Malvaux P., van den Berghe H., Tanghe W., Proemans W. Association d’un syndrome anatomo-pathologique de pseudo-hermaphrodisme masculin, d’un tumeur de Wilms’ d’un nephropathie parenchymateuse et d’un mosaicisme XX/XY. Arch Fr Pediatr 1967; 24: 729-739.

9. Francke U., Holmes L.B., Atkins L., Riccardi V.M. Aniridia-Wilms’ tumor association: evidence for specific deletion of 11p13. Cytogenet Cell Genet 1979; 24: 185-192.

10. Frasier S.D., Bashore R.A., Mosier H.D. Gonadoblastoma associated with pure gonadal dysgenesis in monozygotic twins. J Pediatr 1964; 64: 740-745.

11. Furchshuber A., Jean G., Gribouval O. et al. Mapping a gene (SRNI) to chromosome 1q25-q31 in idiopathic nephrotic syndrome confirms a distinct entity of autosomal recessive nephrosis. Hum Mol Genet 1995; 4: 2155-2158.

12. Holmberg Ch., Antikainen M., Ronnholm K. et al. Management of congenital nephrotic syndrome of the Finnish type. Pediatr Nephrol 1995; 9: 10-16.

13. Jeanpierre C., Beroud C., Niaudet P., Junien C. Software and database for the analysis of mutations in the human WT1 gene. Nucleic Acids Res 1998; 26: 271-274.

14. Knudson A.G.Jr., Strong L.C. Mutation and cancer: a model for Wilms’ tumor of the kidney. J Natl Cancer Inst 1972; 48: 313-324.

15. Koziell А., Grundy R. Frasier and Denys-Drash syndromes: different disorders or part of a spectrum? Arch Dis Child 1999; 81: 365-369.

16. Kreidberg J.A., Sariola H., Loring J.M. et al. WT-1 is required for early kidney development. Cell 1993; 74: 679-691.

17. Little M., Holmes G., Bickmore W., van Heyningen V., Hastie N., Wainwright B. DNA binding capacity of the WT1 protein is abolished by Denys-Drash syndrome WT1 point mutations. Hum Mol Genet 1995; 4: 351-358.

18. Montgomery B., Kelais P., Blute M. et al. Extended follow up of bilateral Wilms’ tumour: results of the national Wilms’ tumour study. J Urol 1991; 146: 514-518.

19. Mueller R.F. The Denys-Drash syndrome. J Med Genet 1994; 31: 471-477.

20. Overzier С. Ein XX/XY Hermaphrodit mil einem «intratubularem Ei» und einem Gonadoblastom (Gonocytom III). Klin Wschr 1964; 42: 1052-1056.

21. Pritchard-Jones K., Fleming S., Davidson D. et al. The candidate Wilms’ tumour gene is involved in genitourinary development. Nature 1990; 346: 194-197.

22. Schumacher V., Scharer K., Wuhl E. et al. Spectrum of early onset nephrotic syndrome associated with WТ1 missense mutations. Kidney Int 1998; 53: 1594-1600.

23. Zunin C., Soave F. Association of nephrotic syndrome and nephroblastoma in sibblings. Ann Paediat 1964; 29: 283-287.