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RecruitingNCT00033137Updated Sep 22, 2026

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

An observational study in Kidney Neoplasms, Kidney Cancer and Pneumothorax, sponsored by National Cancer Institute (NCI). Recruiting at 1 site in United States. Open to participants aged 2 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-22.

Sponsored by National Cancer Institute (NCI) · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
950
Ages
2 Years and older
Sex
All
01

Study 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.

Read the 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:

-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.
02

Conditions studied

  • Kidney Neoplasms
  • Kidney Cancer
  • Pneumothorax
  • FLCN Protein, Human

Keywords

  • Pneumothorax
  • Kidney
  • Fibrofolliculoma
  • BHD
  • Neoplasms
  • Natural History
03

Who can participate

Ages eligible
2 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

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, a biological relative of an individual with a confirmed diagnosis of BHD. Individuals with a known germline FLCN mutation

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

EXCLUSION CRITERIA:

None.

04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
950 participants (estimated)

Groups and cohorts

  • 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.)

05

What researchers measure

Primary outcomes

  1. Identify genotype / phenotype correlations.

    Collection of blood, saliva, tissue \& urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer

    Time frame: on-going

  2. Determine risk of renal cancer, lung cysts and fibrofollicullomas in patients with BHD.

    Collection of blood, saliva, tissue \& urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer

    Time frame: on-going

  3. Determine if other genes contribute to BHD.

    Collection of blood, saliva, tissue \& urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer

    Time frame: on-going

  4. Define types and characteristics (including patterns of growth) of renal cancer associated with BHD.

    Collection of blood, saliva, tissue \& urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer

    Time frame: on-going

  5. Define the natural history of BHD related renal tumors.

    Collection of blood, saliva, tissue \& urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer

    Time frame: on-going

06

Study locations

1 of 1 sites recruiting
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    • For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) · Contact · ccopr@nih.gov · 800-411-1222
    Recruiting
07

References and documents

Individual participant data

Plan to share: Yes — All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Supporting information: Study protocol, Sap, Icf

08

Registry details

Key details

Study ID
NCT00033137
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Apr 8, 2002
Start date
May 13, 2002
Last update
Sep 22, 2026

Study contacts

Deborah A Nielsen, R.N.
Contact
deborah.nielsen@nih.gov
(240) 760-6247
W. Marston Linehan, M.D.
Contact
linehanm@mail.nih.gov
(240) 858-3700
W. Marston Linehan, M.D.
principal investigator · National Cancer Institute (NCI)

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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