The case of observing a patient with WT1 gene mutation in exone 7 with bilateral Wilms metachronous tumor, disturbance of the sex formation in the form of scrotal hypospadias and bilateral abdominal cryptorchidism, without nephropathy, is presented. The child underwent surgical operations: left-sided nephrectomy, resection of the lower pole of the right kidney, bilateral orchiopexy and two-stage hypospadias correction. 7 years after the start of treatment and 3 years after the final operation, the condition of the child was estimated as satisfactory. The presented case by the results of the molecular genetic study has no previously described analogues and requires further observation.
Rationale:
Pediatric patients with WTl-associated syndromes (including Wilms’ tumor-aniridia syndrome and Denys-Drash syndrome), Perlman syndrome, mosaic aneuploidy, and Fanconi anemia with a biallelic breast cancer type 2 susceptibility protein mutation have the highest risk of developing Wilms’ tumor.
Patient concerns and diagnosis:
We describe a patient with bilateral metachronous Wilms’ tumor, ambiguous genitalia characterized by 46, XY disorder of sexual development (DSD) with scrotal hypospadias and bilateral abdominal cryptorchidism, but without nephropathy. At the age of 7 months, the child underwent left nephrectomy with left orchiopexy. At follow-up after 8 months, a second tumor with a diameter of 10 mm was detected in abdominal CT scans at the lower pole of the right kidney.
Intervention:
Intra-operative macroscopic inspection of the right kidney revealed a tight attachment of the right proximal ureter to the tumor. Thus, retroperitoneoscopic resection of the lower pole of the right kidney had to be changed to an open surgical procedure with partial resection of the proximal ureter and high uretero-ureterostomy. We subsequently performed orchiopexy and two-stage correction of hypospadias using a free skin graft.
Outcomes:
At the last follow-up at the age of 8 years, no pathology requiring treatment was noted. A pair-end-reading (2 × 125) DNA analysis with an average coverage of at least 70 to 100 × revealed a previously unknown heterozygous mutation in exon 7 of the Wilms’ tumor suppressor gene 1 (WT1) gene (chr11:32417947G>A), leading to the appearance of a site of premature translation termination in codon 369 (p.Arg369Ter, NM_024426.4). This mutation had not been registered previously in the control samples “1000 genomes,” Exome Sequencing Project 6500, and the Exome Aggregation Consortium. Thus, to the best of our knowledge this represents a newly identified mutation causing incomplete Denys-Drash syndrome.
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