Management of Wilms tumors in Drash and Frasier syndromes.

Background Children with WT1 gene-related disorders such as Denys–Drash syndrome (DDS) and Frasier syndrome (FS) are at increased risk of Wilms tumor and end-stage renal disease. We investigated whether Wilms tumors in these patients displayed a specific phenotype or behavior and whether nephron-sparing surgery was beneficial. Procedure We retrospectively studied all patients with DDS, FS, or other WT1 mutations treated at our institutions between 1980 and 2007. Results We identified 20 patients, of whom 18 had benign or malignant tumors. Wilms tumors occurred in 15 patients, being unilateral in 10 and bilateral in 5 (20 tumors). Median age at Wilms tumor diagnosis was 9 months. No patients had metastases. According to the International Society of Pediatric Oncology Working Classification, there were 19 intermediate-risk tumors and one high-risk tumor; no tumor was anaplastic. In patients with nephropathy who underwent unilateral nephrectomy for Wilms tumor or nephron-sparing surgery for bilateral Wilms tumor, mean time to dialysis was 11 or 9 months, respectively. Other tumors included three gonadoblastomas (in two patients), one retroperitoneal soft-tissue tumor, and one transitional cell papilloma of the bladder. Two patients, both with stage I Wilms tumor, died from end-stage renal disease-related complications. The median follow-up time for the 18 survivors was 136 months (range, 17–224 months). Conclusion Most Wilms tumors in children with WT1-related disorders were early-stage and intermediate-risk tumors, with a young age at diagnosis. In patients without end-stage renal disease, nephron-sparing surgery should be considered for delaying the onset of renal failure. Pediatr Blood Cancer 2009;52:55–59. © 2008 Wiley-Liss, Inc.