- Wilms Tumors are a highly common type of pediatric tumor that arise in the kidneys of children, typically between the ages of 2-5 years. Importantly, Wilms tumors are often observed as part of larger clinical syndromes.
- Wilms tumors are predisposed in children as part of larger syndromes that may be associated with familial mutations or congenital malformations of the kidneys. Wilms tumors are important because they are classic examples of the Two-hit Hypothesis for cancer development. These predisposing syndromes are characterized by germline genetic lesions in one of the alleles of either the WT1 or WT2 gene which are tumor suppressors on Chromosome 11. Because one of the alleles of WT1 or WT2 is defective (i.e. already one "hit") at baseline, these children are highly predisposed to acquiring as second genetic "hit" on the other allele, yielding eventual development of a Wilms tumor.
- Asociated Syndromes
- WAGR Syndrome: This syndrome is associated with deletion of a region of Chromosome 11 which constitutes the first "hit" on WT1
- Denys-Drash Syndrome: Denys-Drash syndrome is characterized by a number of genito-urinary abnormalities and is caused by a germline defect in the WT1 gene
- Beckwith-Wiedemann Syndrome: Beckwith-Wiedemann Syndrome is characterized by multi-organ abnormalities and is caused by a germline defect in the WT2 gene.