TRIM28 congenital predisposition to Wilms’ tumor: novel mutations and presentation in a sibling pair

Wilms’ tumor is the most common renal malignancy in children. In addition to staging, molecular risk stratification, such as loss of heterozygosity (LOH) in Chromosomes 1 and 16, is being increasingly used. Although genetic predisposition syndromes have been well-characterized in some Wilms’ tumors, recent sequencing and biology efforts are expanding the classification of this malignancy. Here we present a case of siblings with remarkably similar presentations of bilateral Wilms’ tumor at ∼12 mo of age. Thorough exam after the younger sibling was diagnosed did not reveal any signs to suggest one of the known Wilms’ predisposition syndromes. Both were treated with standard therapies with good response and long-term sustained complete remission of 53 and 97 mo, respectively. Whole-exome sequencing was performed on a tumor sample from each patient and matched blood from one, revealing a shared truncation mutation of TRIM28 in all three samples with heterozygosity in the germline sample. TRIM28 loss has been recently implicated in early-stage Wilms’ tumors with epithelioid morphology. These siblings expand the phenotype for presentation with multifocal disease with retained excellent response to standard therapy.