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Re: In response to Richard H Scott et al.

Dear Editor,

We read with interest the article by Scott et al. in which the authors review the syndromes and chromosomal abnormalities associated with Wilms tumor (WT) [1].

Although the research criteria described by the Authors were meant to ascertain comprehensively the conditions reported in association with WT, we would like to signal an unusual association that was not reported in an otherwise extremely exhaustive paper.

In 1986 Malpuech et al. [2], reported a patient with a chromosomal deletion in the region 11p13, associated with the WAGR syndrome, and a severe phenotype including toes polydactyly. Following this report, in May 2005 two articles published in the American Journal of Medical Genetics, one by us and the other by a French group, added the description of four WAGR patients showing hallucal polydactyly [3] [4]. Three cases, a girl described in our study and the twin girls of the French study, showed allux bilateral polydactyly, while the remaining WAGR boy, reported by Bremond-Gignac and collegues, had monolateral polydactyly. In all four cases cytogenetic analyses revealed the presence of an interstitial deletion involving chromosome 11p13. In addition, two cases, our patient and one of the twin sisters, were diagnosed with WT.

Assuming a frequency of allux polydactily and of WAGR in the population of approximately 1:40.000 and 1:1.250.000, respectively [5] [6], the expected chance occurrence of individuals with both phenotypes would be approximately 1:5x10e10. The observation of polydactyly in at least five WAGR patients with verified 11p interstitial deletion, indicates a non-random association and the possibility should be considered that polydactyly is another feature related to WAGR and then to an increased risk of WT. The occurrence of polydactily in WAGR patients could be due either to a very low penetrant trait associated with haploinsufficiency of one of the genes present in the critical WAGR region, or to a positional effect of the deletion on a gene mapped close to it.

References

[1] Scott RH, Stiller CA, Walker L, Rahman N. Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. J Med Genet 2006.

[2] Malpuech G, Sultan C, Bertheas MF, Loire C, Renaud H, Francannet C, Vanlieferinghen P. Male pseudohermaphroditism, partial androgen receptors defect, 11p13 deletion: indication of gene localization. Am J Med Genet 1986; 24(4):679-684.

[3] Manoukian S, Crolla JA, Mammoliti P, Testi MA, Zanini R, Carpanelli M, Piozzi E, Sozzi G, De Vecchi G, Terenziani M, Spreafico C, Collini P, Radice P, Perotti D. Bilateral prexial polydactyly in a WAGR syndrome patient. Am J Med Genet A 2005; 134(4):426-429.

[4] Bremond-Gignac D, Gerard-Blanluet M, Copin H, Bitoun P, Baumann C, Crolla JA, Benzacken B, Verloes A. Three patients with hallucal polydactyly and WAGR syndrome, including discordant expression of Wilms tumor in MZ twins. Am J Med Genet A 2005; 134(4):422-425.

[5] Orioli IM, Castilla EE. Thumb/hallux duplication and preaxial polydactyly type I. Am J Med Genet 1999; 82(3):219-224.

[6] Breslow NE, Norris R, Norkool PA, Kang T, Beckwith JB, Perlman EJ, Ritchey ML, Green DM, Nichols KE. Characteristics and outcomes of children with the Wilms tumor-Aniridia syndrome: a report from the National Wilms Tumor Study Group. J Clin Oncol 2003; 21(24):4579-4585.