Hereditary kidney cancer syndromes

Adv Chronic Kidney Dis. 2014 Jan;21(1):81-90. doi: 10.1053/j.ackd.2013.10.001.


Inherited susceptibility to kidney cancer is a fascinating and complex topic. Our knowledge about types of genetic syndromes associated with an increased risk of disease is continually expanding. Currently, there are 10 syndromes associated with an increased risk of all types of kidney cancer, which are reviewed herein. Clear cell kidney cancer is associated with von Hippel Lindau disease, chromosome 3 translocations, PTEN hamartomatous syndrome, and mutations in the BAP1 gene as well as several of the genes encoding the proteins comprising the succinate dehydrogenase complex (SDHB/C/D). Type 1 papillary kidney cancers arise in conjunction with germline mutations in MET and type 2 as part of hereditary leiomyomatosis and kidney cell cancer (fumarate hydratase [FH] mutations). Chromophone and oncocytic kidney cancers are predominantly associated with Birt-Hogg-Dubé syndrome. Patients with Tuberous Sclerosis Complex (TSC) commonly have angiomyolipomas and rarely their malignant counterpart epithelioid angiomyolipomas. The targeted therapeutic options for the kidney cancer associated with these diseases are just starting to expand and are an area of active clinical research.

Keywords: Birt-Hogg-Dube disease; Genetic disease; Genetic susceptibility; Kidney cancer; von Hippel Lindau disease.

Publication types

  • Review

MeSH terms

  • Birt-Hogg-Dube Syndrome / genetics
  • Carcinoma, Renal Cell / genetics*
  • Chromosomes, Human, Pair 3 / genetics
  • Genetic Predisposition to Disease
  • Hamartoma Syndrome, Multiple / genetics
  • Humans
  • Kidney Neoplasms / genetics*
  • Leiomyomatosis / genetics
  • Neoplastic Syndromes, Hereditary / genetics*
  • Proto-Oncogene Proteins c-met / genetics
  • Skin Neoplasms / genetics
  • Succinate Dehydrogenase / genetics
  • Translocation, Genetic / genetics
  • Tuberous Sclerosis / genetics
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin Thiolesterase / genetics
  • Uterine Neoplasms / genetics
  • von Hippel-Lindau Disease / genetics


  • BAP1 protein, human
  • Tumor Suppressor Proteins
  • Succinate Dehydrogenase
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Ubiquitin Thiolesterase

Supplementary concepts

  • Hereditary leiomyomatosis and renal cell cancer