Kidney NeoplasmsNCT00033137
Genetic Analysis of Birt Hogg-Dube Syndrome and Characterization of Predisposition to Kidney Cancer
An observational study of Kidney Neoplasms and Kidney Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and olderHealthy volunteers can take part
- Conditions the study is for
- Kidney Neoplasms, Kidney Cancer, Pneumothorax
- How many people
- 950 participants
- Where
- 1 siteUnited States
- Study dates
- 13 May 2002to not given
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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
Who may be able to join
- 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
Show all 15Show fewer
- --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.
Who cannot join
- None.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: Birt-Hogg-Dub(SqrRoot)(Copyright) Syndrome: Characterization of the FLCN Disease Gene and Predisposition to Renal Cancer, Cutaneous Fibrofolliculoma and Pulmonary Cysts
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
Read more
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.
- Conditions
- Kidney Neoplasms, Kidney Cancer, Pneumothorax, FLCN Protein, Human
- Keywords
- Pneumothorax, Kidney, Fibrofolliculoma, BHD, Neoplasms, Natural History
- Medical subject headings
- Kidney Neoplasms, Pneumothorax, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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.) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify genotype / phenotype correlations.
Collection of blood, saliva, tissue \& urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer
Measured: on-going
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
Measured: on-going
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
Measured: on-going
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
Measured: on-going
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
Measured: on-going
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2002 (estimated)
- Study start13 May 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney NeoplasmsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 950 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- W. Marston Linehan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00033137
- Sponsor's protocol ID
- 020159
- Other IDs
- 02-C-0159
- Status last verified
- 2 Nov 2026
- First submitted
- 5 Apr 2002
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Birt-Hogg-Dub(SqrRoot)(Copyright) Syndrome: Characterization of the FLCN Disease Gene and Predisposition to Renal Cancer, Cutaneous Fibrofolliculoma and Pulmonary Cysts
- ClinicalTrials.gov ID
- NCT00033137
- Acronym / sponsor ID
- 020159
- Conditions
- Kidney Neoplasms, Kidney Cancer, Pneumothorax, FLCN Protein, Human
- Keywords
- Pneumothorax, Kidney, Fibrofolliculoma, BHD, Neoplasms, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 950 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 13 May 2002 (actual)
- First posted
- 8 Apr 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
-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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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.) |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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
Key inclusion criteria (15 listed)
- -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
Key exclusion criteria (1 listed)
- None.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identify genotype / phenotype correlations.
Time frame: on-going
Collection of blood, saliva, tissue \& urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer
Determine risk of renal cancer, lung cysts and fibrofollicullomas in patients with BHD.
Time frame: on-going
Collection of blood, saliva, tissue \& urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer
Determine if other genes contribute to BHD.
Time frame: on-going
Collection of blood, saliva, tissue \& urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer
Define types and characteristics (including patterns of growth) of renal cancer associated with BHD.
Time frame: on-going
Collection of blood, saliva, tissue \& urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer
Define the natural history of BHD related renal tumors.
Time frame: on-going
Collection of blood, saliva, tissue \& urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
W. Marston Linehan, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Kidney Neoplasms and Kidney Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Deborah A Nielsen, R.N. ((240) 760-6247, deborah.nielsen@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identify genotype / phenotype correlations. (time frame: on-going). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.