The Birt-Hogg-Dube (BHD) syndrome describes the combined appearance of cutaneous lesions, kidney tumors, and pulmonary cysts, which in some cases are associated with pneumothorax.
Kidney tumors vary widely from benign oncocytomas (5%) to malignant, clear cell (75%), chromophobic (5%) or papillary (15%) renal cell carcinomas. Mixed kidney tumors also occur occasionally. The tumors usually develop only after the appearance of the skin lesions, which usually occur in the 3rd and 4th year of life and persist later on.
The most common dermatological symptom is fibrofolliculoma, benign tumors of the hair follicle. They resemble small, pale skin nodules on the face, neck, ears and upper body. They usually occur for the first time at the beginning of their 20th year and worsen with advancing age. Other skin lesions include acrochordon and trichodiscoma.
The lung cysts, varying in size from microscopic foci to a few millimeters in diameter, are characterized by cystic enlargement of the alveolar spaces. Their thin walls are lined with cuboid epithelium. Under the pressure of inhalation, the cysts break and cause pneumothorax.
Cause are mutations in the FLCN gene at the genome 17p11.2, which codes for folliculin. The function of folliculin is not yet known. It is thought to be a component of mTOR signaling and is important in the development of kidney tumors and other changes. The inheritance is autosomal dominant.