Background
Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant disorder clinically manifested by fibrofolliculomas, renal cell carcinoma, lung cysts, and spontaneous pneumothorax.
In 1977, Birt, Hogg, and Dubé reported small papular skin lesions distributed over the scalp, forehead, face, and neck in 15 of 70 members in a kindred study. Histologic examination of the lesions revealed fibrofolliculomas, trichodiscomas, and acrochordons. The presence of this triad has been termed Birt-Hogg-Dubé syndrome.
However, evidence suggests that these three lesions may actually represent only one lesion, the fibrofolliculoma, cut in various planes of section or during different stages of maturation.
Multiple or bilateral renal carcinomas have been reported in association with this syndrome, most commonly hybrid oncocytic tumors with features of chromophobe renal carcinoma (50%), followed by chromophobe renal cancer, clear cell renal carcinoma, and renal oncocytoma.
Of patients with Birt-Hogg-Dubé syndrome, 12-34% develop renal tumors, typically in the fourth and fifth decades of life.
Pulmonary cysts and spontaneous pneumothoraces have also been increasingly reported manifestations of Birt-Hogg-Dubé syndrome.
Pulmonary cyst are present in 24-95% of Birt-Hogg-Dubé patients.
Additionally, the overall risk of having a pneumothorax in patients with Birt-Hogg-Dubé syndrome is 29%.
Even with these pulmonary complications of Birt-Hogg-Dubé syndrome, most patients have preserved pulmonary function or mild obstructive pulmonary disease.
Other, less commonly associated features include a large connective-tissue nevus, parathyroid adenomas, flecked chorioretinopathy, bullous emphysema, lipomas, angiolipomas, parotid oncocytomas, multiple oral mucosal papules, neural tissue tumors (including neurilemomas), multiple facial angiofibromas, and desmoplastic melanoma.
Colonic polyps and colonic adenocarcinoma had previously been described with Birt-Hogg-Dubé syndrome; however, several large cohort studies failed to demonstrate such findings.
Additionally, medullary thyroid cancer was reported in nine members of the original family described by Birt, Hogg, and Dubé, but it has not been reported in subsequent cases. A case of neuroendocrine cancer of prostate or bladder origin has also been reported.