Bilateral Wilms’ tumor in a child with Denys-Drash syndrome: novel frameshift variant disrupts the WT1 nuclear location signaling region

Abstract Objectives Wilm’s Tumor (WT) is the most common pediatric kidney cancer. Whereas most WTs are isolated, approximately 5% are associated with syndromes such as Denys-Drash (DDS), characterized by early onset nephropathy, disorders of sex development and predisposition to WT. Case presentation A 46,XY patient presenting with bilateral WT and genital ambiguity without nephropathy was heterozygous for the novel c.851_854dup variant in WT1 gene sequence. This variant affects the protein generating the frameshift p.(Ser285Argfs*14) that disrupts a nuclear localization signal (NLS) region. Conclusions This molecular finding is compatible with the severe scenario regarding the Wilm’s tumor presented by the patient even though nephropathy was absent.