Wilms tumors, a rare form of kidney cancer that typically affects children, can be caused by high-penetrance genetic or epigenetic factors. However, studies systematically examining both these aspects of the disease are scarce. In a new study, researchers offered germline whole-genome sequencing to all participants diagnosed with Wilms tumors from 2016 to 2021 in Denmark. Across 24 patients, they found that a third had either genetic predisposition or an indicator of susceptibility to Wilms tumors. This third of patients was exclusively female, suggesting that the majority of Wilms tumors in females may have underlying (epi)genetic origins. With this, the study sheds light on the long-observed, yet unexplained, overrepresentation of females among patients with Wilms tumor and underscores the importance of carefully evaluating patients genetically to facilitate early detection of underlying predisposition, which could impact treatment, follow-up, and genetic counseling. (By Dr. Ulrik Kristoffer Stoltze, https://jmg.bmj.com/content/early/2023/04/04/jmg-2022-108982 )