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.

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

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.

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.

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.

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.

European urology. 2019 Jul 17 [Epub ahead of print]

Maria I Carlo, A Ari Hakimi, Grant D Stewart, Gennady Bratslavsky, James Brugarolas, Ying-Bei Chen, W Marston Linehan, Eamonn R Maher, Maria J Merino, Kenneth Offit, Victor E Reuter, Brian Shuch, Jonathan A Coleman

Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: ., Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK., Upstate Medical University, Syracuse, New York, NY, USA., UT Southwestern Medical Center, Dallas, TX, USA., National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; Department of Medical Genetics, University of Cambridge and NIHR Cambridge Biomedical Research Centre, and Cancer Research UK Cambridge Cenre, Cambridge, UK., David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.