Familial Kidney Cancer: Implications of New Syndromes and Molecular Insights

Eur Urol. 2019 Dec;76(6):754-764. doi: 10.1016/j.eururo.2019.06.015. Epub 2019 Jul 18.


Context: Hereditary cases account for about 5% of all cases of renal cell carcinoma (RCC). With advances in next-generation sequencing, several new hereditary syndromes have been described in the last few years.

Objective: To review and summarise the recent preclinical and clinical literature in hereditary renal cancer.

Evidence acquisition: A systematic review of the literature was performed in November 2018 using PubMed and OMIM databases, with an emphasis on kidney cancer, genetics and genomics, clinical criteria, and management.

Evidence synthesis: Several autosomal dominant hereditary RCC syndromes have been described, including those related to germline pathogenic variants in VHL, MET, FH, TSC1/TSC2, FLCN, SDHA/B/C/D, BAP1, CDC73, and MITF. Clinical spectrum of SDH, BAP1, and MITF is still being defined, although these appear to be associated with a lower incidence of RCC. FH and likely BAP1 RCC are associated with more aggressive disease. Preclinical and clinical studies show that using systemic therapy that exploits specific genetic pathways is a promising strategy.

Conclusions: There are several well-described hereditary RCC syndromes, as well as recently identified ones, for which the full clinical spectrum is yet to be defined. In the new era of precision medicine, identification of these syndromes may play an important role in management and systemic treatment selection.

Patient summary: This review covers updates in the diagnosis and management of familial kidney cancer syndromes. We describe updates in testing and management of the most common syndromes such as von Hippel-Lindau, and hereditary leiomyomatosis and renal cell carcinoma. We also provide insights into recently described familial kidney cancer syndromes.

Keywords: Birt-Hogg-Dubé syndrome; Genetic counselling; Hereditary cancer; Hereditary leiomyomatosis renal cell carcinoma; Hereditary papillary renal cell carcinoma; Kidney cancer; Renal cell carcinoma; Tuberous sclerosis complex; von Hippel-Lindau disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / therapy
  • Humans
  • Leiomyomatosis / diagnosis
  • Leiomyomatosis / genetics
  • Leiomyomatosis / therapy
  • Neoplastic Syndromes, Hereditary / diagnosis
  • Neoplastic Syndromes, Hereditary / genetics
  • Neoplastic Syndromes, Hereditary / therapy
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / genetics
  • Skin Neoplasms / therapy
  • Syndrome
  • Tuberous Sclerosis / diagnosis
  • Tuberous Sclerosis / genetics
  • Tuberous Sclerosis / therapy
  • Uterine Neoplasms / diagnosis
  • Uterine Neoplasms / genetics
  • Uterine Neoplasms / therapy
  • von Hippel-Lindau Disease / diagnosis
  • von Hippel-Lindau Disease / genetics
  • von Hippel-Lindau Disease / therapy

Supplementary concepts

  • Familial renal cell carcinoma
  • Hereditary leiomyomatosis and renal cell cancer