Hereditary Renal Cell Carcinoma

Abstract

Hereditary renal cell carcinoma (RCC) is estimated to comprise 3% to 5% of all RCC. Since the manifestations that are associated with hereditary RCC syndromes are not well recognized by most clinicians, hereditary RCC may be underreported. Diagnostic criteria including multiple and/or bilateral renal tumors, a young age at diagnosis, a positive family history for RCC, a particular histological type of RCC, and extrarenal manifestations are suggestive of hereditary RCC. Hereditary RCC is a heterogeneous disorder comprised of a variety of hereditary syndromes caused by different gene alterations, including von Hippel-Lindau (VHL) disease, hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis renal cell carcinoma (HLRCC), hereditary head and neck paragangliomas (HPGL) and pheochromocytomas (PCC) (SDH-RCC), Birt-Hogg-Dube syndrome (BHDS), tuberous sclerosis complex (TSC), Cowden syndrome (CS), and BAP1 cancer susceptibility syndrome. All of these syndromes are associated with a germline mutation in a specific causative gene and are inherited in an autosomal dominant manner. In this chapter, clinical manifestations, genetics, and molecular functions of the responsible genes will be presented for each hereditary RCC susceptibility syndrome.