Table 1.

Overview of major hereditary renal cell cancer syndromes.

Adapted from Menko and Maher [1]

Syndrome	Inheritance	Gene	Estimated RCC risk	Renal tumour histological subtypes	Functional consequences of mutation
Von Hippel–Lindau disease	AD	VHL	70%	Clear cell RCC	Activation of hypoxic response pathways
Birt–Hogg–Dubé syndrome	AD	FLCN	25%	Various, but hybrid chromophobe/oncocytic RCC typical	Activation of the mTOR pathway
Hereditary type 1 papillary RCC	AD	MET	Increased	Papillary type 1 RCC	Activation of MET signalling pathway
Hereditary leiomyomatosis and renal cell cancer	AD	FH	15%	Papillary type 2 RCC	Activation of hypoxic response pathways Epigenetic changes (e.g. DNA methylation)
Succinate dehydrogenase subunit-related RCC	AD	SDHB SDHD a SDHC SDHA	Highest risk (up to 10–15% with SDHB	Various types, but specific features recognised	Activation of hypoxic response pathways Epigenetic changes (e.g. DNA methylation)
Chromosome 3 translocations	Chromosomal	Chromosome 3	Increased (up to 70%)	Clear cell RCC	Loss of translocated chromosome 3p and somatic mutation of VHL leads to activation of hypoxic response pathways
PTEN hamartoma tumour syndrome	AD	PTEN	5–35%	Mostly papillary RCC	Activation of phosphoinositide 3-kinase (PI3K) signalling pathway
Hereditary BAP1 tumour syndrome	AD	BAP1	Increased	Clear cell	BAP1 inactivation associated with altered chromatin architecture, DNA damage response and cell cycle regulation

AD autosomal dominant, RCC renal cel carcinoma

^aInheritance is characterised by maternal imprinting