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

Background:

• Birt-Hogg-Dube (BHD) is a rare, autosomal dominantly inherited disorder which confers susceptibility to develop multifocal, bilateral renal cancer, spontaneous pneumothorax and fibrofolliculomas.
• BHD is caused by mutations in the FLCN gene located on Chromosome17p11.2
• Defining the genetic and biochemical pathways leading to renal tumorigenesis in BHD may lead to the development of new molecularly targeted drugs.

Objectives:

• To define the types and characteristics (including patterns of growth) of renal cancer associated with BHD
• To determine the risk of renal cancer, lung cysts and fibrofolliculomas in individuals with BHD
• To define the natural history of BHD related renal tumors
• To determine if other genes contribute to BHD
• Identify genotype/phenotype correlations

Eligibility:

-Individuals that meet one or more of the following criteria:

--Suspected or known to have phenotype or genotype suggestive of Birt-Hogg-Dube (BHD), such as:

• Individuals with histologically confirmed fibrofolliculomas
• Individuals with clinical evidence of multiple skin papules consistent with fibrofolliculomas, and/or a family history of spontaneous pneumothorax or kidney cancer
• Individuals with a known germline FLCN mutation

or

--Renal tumor histology consistent with BHD, including, but not limited to those suggestive of chromophobe, hybrid oncocytic neoplasm or oncocytoma

or

--Are a relative (related by blood) of an individual with a confirmed or suspected diagnosis of BHD

Design:

• These rare families will be recruited to genetically confirm diagnosis, determine size and location of renal tumors, size at presentation, growth rate and metastatic potential of renal tumors.
• Genetic testing will be offered to gain appreciation of the effect of mutations the BHD gene and to assess the relative activity of various germline and somatic mutations.
• We will determine if there is a relationship between mutation and disease manifestations and phenotype.

• INCLUSION CRITERIA:

Individuals that meet one or more of the following criteria:

-Suspected or known to have phenotype or genotype suggestive of Birt-Hogg-Dube (BHD), such as:

--Individuals with at least one histologically confirmed fibrofolliculomas;

or

--Individuals with clinical evidence of multiple skin papules (without fibrofolliculoma biopsy confirmation) and a personal or family history of spontaneous pneumothorax/or kidney cancer;

or

--Individuals with spontaneous pneumothorax and skin papules or kidney cancer and a positive family history of spontaneous pneumothorax, skin papules or kidney cancer;

or

--Individuals with a known germline FLCN gene mutation

OR

-Renal tumor histology consistent with BHD, including, but not limited to those suggestive of chromophobe, hybrid oncocytic neoplasm or oncocytoma.

OR

• Are a relative (related by blood) of an individual with a confirmed or suspected diagnosis of BHD.

-Participants must be >= 2 years of age.

• For children less than 18 years of age, parental permission or legal guardian consent will be obtained.

Exclusion criteria

None.