VHL and von Hippel-Lindau disease: However, exceptions exist: although von Hippel–Lindau disease is a major cause of familial clear cell renal carcinoma (cRCC) and somatic inactivation of the VHL tumour suppressor gene (TSG) occurs in most sporadic cRCC (Gnarra et al, 1994; Foster et al, 1994; Herman et al, 1994; Clifford et al, 1998), somatic VHL inactivation by mutation or methylation of the promoter region is infrequent (<5%) in sporadic phaeochromocytomas.