NCT00033137RecruitingNot Applicable

Birt-Hogg-Dub(SqrRoot)(Copyright) Syndrome: Characterization of the FLCN Disease Gene and Predisposition to Renal Cancer, Cutaneous Fibrofolliculoma and Pulmonary Cysts

National Cancer Institute (NCI)1 site in 1 country950 target enrollmentStarted: May 13, 2002Last updated: September 28, 2026

Conditions

Trial Snapshot

Phase: Not Applicable
Status: Recruiting
Sponsor: National Cancer Institute (NCI)
Enrollment: 950
Locations: 1
Primary Endpoint: Identify genotype / phenotype correlations.

Study Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Study Overview

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

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.

...

Detailed Description

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:

Study Design

Study Type: Observational
Observational Model: Cohort
Time Perspective: Prospective

Eligibility Criteria

Ages: 2 Years to — (Child, Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: Yes

Inclusion Criteria

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

Not provided

Arms & Interventions

Family Members

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

Individuals

Individuals with phenotype or genotype suggestive of Birt Hogg Dub(SqrRoot)(Copyright) and/or Renal tumor histology consistent with BHD

Non-Biologic Family Members

Spouses enrolled primarily for linkage analysis (Spouses have been removed from the inclusion criteria for this study. This closed cohort has been created for spouses previously enrolled on study.)