Chapter 14: Hereditary Renal Cancer Syndromes

Inherited forms of renal cancer are estimated to account for 2%–5% of all kidney cancer (1). Currently, 10 inherited cancer susceptibility syndromes are definitively associated with an increased risk of renal cancer (Table 1) and are described in more detail below. Patients with these inherited syndromes develop kidney cancer at an earlier age; furthermore, the lesions can be multifocal, bilateral, and heterogeneous. Several, including Birt-Hogg-Dubé syndrome (BHD), familial clear cell renal cancer due to chromosome3 translocation, hereditary papillary renal cancer, hereditary leiomyomatosis and renal cell cancer (HLRCC), and von Hippel-Lindau disease (vHL) have renal cancer as a primary feature, whereas in another inherited cancer susceptibility syndrome, such as BAP1 mutation–associated disease, Lynch syndrome, phosphatase and tensin homologue (PTEN) hamartoma syndrome, hereditary pheochromocytoma and paraganglioma (due to SDHx mutations), and tuberous sclerosis complex, it is a secondary feature. Recently, mutations in CDKN2B and PBRM1 also have been reported to predispose to clear cell renal cancer in single case series (2,3) and, as such, need further validation.Manyof the genes identified through the studies of familial renal cancerhaveproven toplay a critical role in renal cancer development through somatic mutation, with vHL disease being the exemplar of this paradigm.Thedescriptionof familieswith inherited cancer susceptibility syndromes associatedwith an increased risk of renal cancer has and will lead to the discovery of mutated genes important in the pathogenesis of renal cancer. Below, the features of the inherited cancer susceptibility syndromes associated with an increased risk of renal cancer, with a focus on the renal manifestations and pathologic features, are reviewed.