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

Introduction

• Org Study ID: 020159
• NTC ID: NCT00033137
• Lead Sponsor Name: National Cancer Institute (NCI)
• Status: Recruiting

Conditions

• Birt-Hogg-Dube Syndrome

Brief Summary

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

Patients 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. Patients 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.

Eligibility Criteria

-INCLUSION CRITERIA:

Patients suspected or known to have phenotype or genotype suggestive of Birt-Hogg-Dube, such as:

Patients with at least one histologically confirmed fibrofolliculomas, or
Patients with clinical evidence of multiple skin papules (without fibrofolliculoma biopsy confirmation) and a personal or family history of spontaneous pneumothorax / or kidney cancer, or
Patients with spontaneous pneumothorax and skin papules or kidney cancer and a positive family history of spontaneous pneumothorax, skin papules or kidney cancer, or
Patients with a known germline FLCN gene mutation
Renal tumor histology consistent with BHD, including, but not limited to those suggestive of chromophobe, oncocytic neoplasm or oncocytoma.

All patients and guardians, for children younger than 18 years of age, must sign an informed consent document indicating their understanding of the investigational nature and the risks of this study before any protocol related studies are performed. Patients

under the age of 18 but who are age 13 or older will be asked to sign an assent document prior to participation.

Participants must be greater than or equal to 2 years of age.
A relative (related by blood) of a patient with a confirmed or suspected diagnosis of BHD.

EXCLUSION CRITERIA:

NONE