Bilateral Renal Tumour as Indicator for Birt-Hogg-Dubé Syndrome

Birt-Hogg-Dubé (BHD) syndrome is a cancer disorder caused by a pathogenic FLCN mutation characterized by fibrofolliculomas, lung cysts, pneumothorax, benign renal cyst, and renal cell carcinoma (RCC). In this case we describe a patient with bilateral renal tumour and a positive familial history for pneumothorax and renal cancer. Based on this clinical presentation, the patient was suspected for BHD syndrome, which was confirmed after molecular testing. We discuss the importance of recognizing this autosomal dominant cancer disorder when a patient is presented at the urologist with a positive family history of chromophobe renal cell cancer or a positive familial history for renal cell cancer and pneumothorax. 1. Background Birt-Hogg-Dubé syndrome (BHDS) was originally described in 1977 and is nowadays known as a rare autosomal dominant cancer disorder characterized by fibrofolliculomas, lung cysts, pneumothorax, benign renal cyst, and renal cell carcinoma (RCC). The mutated gene for BHD encodes the protein folliculin (FLCN) which acts as a tumour suppressor and interacts with mTOR and AMPK signalling pathways [1]. Here we report a case of a patient with bilateral renal cancer and a positive familial history for pneumothorax and renal cancer. Based on the bilateral renal tumour and the positive family history for renal cancer and pneumothorax, Birt-Hogg-Dubé syndrome was suspected. 2. Case Report In March 2011, a 44-year-old Caucasian male was evaluated for urolithiasis. He had no physical complaints, macroscopic haematuria, or weight loss. His medical and social history were unremarkable; he never smoked. His father had been treated for colorectal cancer; his mother had three episodes of spontaneous pneumothorax and had been treated for a renal tumour. Physical examination of the abdomen showed no abnormalities. Routine laboratory tests were normal. Computed tomography (CT) of the abdomen showed an interpolar tumour in the left kidney, diameter 14？mm (Figure 1(a), arrow), and a second tumour in the upper pole of the right kidney, diameter 8？mm (Figure 1(b), arrow). After a needle biopsy of the largest tumour, revealing a chromophobe renal cell carcinoma (Figures 2(a) and 2(b)), the tumour in the left kidney was treated with radio frequency ablation (RFA). The CT findings in combination with the positive family history for renal cancer and his mother’s episodes of pneumothorax suggested Birt-Hogg-Dubé (BHD) syndrome. Sequencing of the FLCN gene showed a pathogenic heterozygous frameshift mutation (c.155delc; p.Leu518Phefs*19)—which has not been described