Individuals with BHD syndrome are predisposed to develop bilateral multifocal tumours of the kidneys which has implications for clinical management, since regular surveillance of the kidneys is required to monitor tumour growth and size, and surgery is inevitably required to excise these tumours. (Birt et al, 1977; Toro et al, 1999; Zbar et al, 2002). Chromophobe renal cancer and a mixed pattern of chromophobe and oncocytic renal tumours are typical for patients with BHD. However, other histological subtypes can occur, including clear-cell and papillary carcinoma, and several mixed patterns (Pavlovich et al, 2002; Pavlovich et al, 2005; Fahmy et al, 2007; Janitzky et al, 2008; Kluijt et al, 2009). Relatively few patients with BHD and metastatic renal cancer have been described in literature (Kluijt et al, 2009; Souza et al, 2005). Prospective studies using cohorts are required to clarify the exact mechanisms of renal carcinogenesis in BHD syndrome (Toro et al, 2008).

Loss of FLCN expression in sporadic renal RCC suggests that FLCN is involved in the normal cellular functions that regulate growth and proliferation in the kidney and that the aberrant functioning of FLCN is mechanism of pathogenesis in both sporadic and BHD related renal carcinogenesis (Gad et al, 2007; Woodward et al, 2008).

Renal cancer is the most life-threatening complication associated with BHD Syndrome and various studies have reported the incidence of renal cancer in individuals with BHD syndrome, with the mean age of RCC incidence described as 50.4 years (Pavlovich et al, 2002) and the earliest reported age at diagnosis of renal cancer in a patient with BHD syndrome being twenty years old (Khoo et al, 2002). Further difficulties in establishing the risk of renal cancer in BHD patients include the possible under diagnosis of BHD Syndrome, variations (interfamilial or otherwise) in cancer risk due to different types of germline FLCN mutations and differences in genetic background.

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References