To the Editors:
We read with interest the recent article by Fröhlich et al. 1, wherein the authors reported two new disease-associated DNA sequence alterations in FLCN, the tumour suppressor gene located at chromosome 17p11.2 which, when mutated, leads to the genodermatosis Birt–Hogg–Dubé syndrome (BHDS). However, we feel that there is an important point that deserves greater prominence.
BHDS was named after three Canadian dermatologists who, in 1977, described 15 adults in a kindred of 70 who had multiple small, dome-shaped papular skin lesions, presenting at >25 yrs of age, over the scalp, forehead, face and neck, with scattered lesions on the chest and back 2. Histologically, these lesions were confirmed to be fibrofolliculomas, benign hamartomas of the hair follicle. Subsequently, this syndrome was found to be a marker of internal disease, as cases of recurrent pneumothorax, lung cysts 3 and renal tumours 3, 4 were reported.
BHDS has now been recognised as one of the inherited renal cancer syndromes, which include von Hippel Lindau, hereditary papillary renal carcinoma and hereditary leiomyomatosis renal cell carcinoma 5. Renal tumours have been reported in as many as 34% of individuals with germline FLCN mutations 6. They are frequently multiple and bilateral, and present at a mean age of 50.7 yrs 7. The most common histological subtypes are hybrid oncocytic (50%) and chromophobe (34%) renal cell carcinoma, while clear cell, oncocytoma and papillary renal cell cancer are less frequently found 7. Radiographic screening is recommended, with a typical strategy involving abdominal computed tomography and/or renal ultrasound at the time of diagnosis, followed by interval screening every 3–5 yrs 8. Parenchyma-sparing surgery is recommended given the risk of development of further tumours 7. In line with these recommendations, all participants in the study by Fröhlich et al. 1 were screened for kidney manifestations by abdominal ultrasound and none were identified.
The importance of recognising the possibility of a diagnosis of Birt–Hogg–Dubé syndrome in patients with familial recurrent pneumothorax, with or without characteristic skin findings, lies in undertaking surveillance for renal tumours, a potentially lethal feature of this syndrome.
Statement of interest
None declared.
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