Genetic AnalysisGenetic Analysis of Birt Hogg-Dube Syndrome and Characterization of Predisposition to Kidney Cancer

This study will investigate the genetic cause of Birt Hogg-Dube (BHD) syndrome and the relationship of this disorder to kidney cancer. BHD is a rare inherited condition characterized by papules, or bumps-benign tumors involving hair follicles-on the head and neck. People with BHD are at increased risk of developing kidney cancer. Scientists have identified the chromosome (strand of genetic material in the cell nucleus) that contains the BHD gene and the region of the gene on the chromosome. This study will try to learn more about:

• The characteristics and type of kidney tumors associated with BHD
• The risk of kidney cancer in people with BHD
• Whether more than one gene causes BHD
• The genetic mutations (changes) responsible for BHD

Individuals with known or suspected Birt Hogg-Dube syndrome, and their family members, may be eligible for this study. Candidates will be screened with a family history and review of medical records, including pathology reports for tumors, and films of computed tomography (CT) and magnetic resonance imaging (MRI) scans.

Participants may undergo various tests and procedures, including the following:

• Physical examination
• Review of personal and family history with a cancer doctor, cancer nurses, kidney surgeon, and genetic counselor
• Chest and other x-rays
• Ultrasound (imaging study using sound waves)
• MRI (imaging study using radiowaves and a magnetic field)
• CT scans of the chest and abdomen (imaging studies using radiation)
• Blood tests for blood chemistries and genetic testing
• Skin evaluation, including a skin biopsy (surgical removal of a small skin tissue sample for microscopic evaluation)
• Cheek swab or mouthwash to collect cells for genetic analysis
• Lung function studies
• Medical photography of skin lesions

These tests will be done on an outpatient basis in either one day or over 3 to 4 days. When the studies are complete, participants will receive counseling about the findings and recommendations. Individuals with kidney lesions may be asked to return periodically, such as every 3 to 36 months, based on their individual condition, to document the rate of progression of the lesions.