On this page
Birt-Hogg-Dubé syndrome
People with Birt-Hogg-Dubé syndrome typically develop characteristic skin growths, lung cysts that may increase the risk of collapsed lung, and have an elevated risk of kidney tumours. The condition follows an autosomal dominant inheritance pattern and can vary considerably in severity between affected individuals.
Available at Jeen Health
Clinical tests that include this
Overview
Birt-Hogg-Dubé syndrome is a rare genetic condition that primarily affects three body systems: the skin, lungs and kidneys. The condition was first described in 1977 by Canadian physicians Birt, Hogg and Dubé, who identified a family with distinctive skin lesions and an increased occurrence of kidney tumours. Exact prevalence is not well established, though the condition is recognised as rare and may be underdiagnosed because features can be subtle or develop gradually over time.
The syndrome arises from pathogenic variants in FLCN, which encodes a protein called folliculin that helps regulate how cells grow and divide. When folliculin function is disrupted, cells in certain tissues become more prone to abnormal growth, leading to the characteristic features of the condition. Most people with Birt-Hogg-Dubé syndrome will develop some combination of skin lesions, lung cysts and kidney abnormalities, though the specific pattern and severity varies widely between individuals and even within the same family. Early recognition of the condition is valuable because it enables appropriate surveillance for kidney tumours and management strategies to reduce the risk of lung-related complications.
Symptoms & clinical features
The most common early sign of Birt-Hogg-Dubé syndrome is the appearance of small, dome-shaped skin growths called fibrofolliculomas, typically beginning in a person's twenties or thirties. These benign lesions usually develop on the face, neck and upper trunk, particularly around the nose, forehead and ears. Fibrofolliculomas are flesh-coloured or slightly paler than surrounding skin and generally cause no discomfort, though some people find them cosmetically concerning. Alongside fibrofolliculomas, individuals may develop similar growths called trichodiscomas or skin tags in the same distribution.
Lung involvement manifests as multiple cysts scattered throughout both lungs, which are typically detected on chest imaging rather than causing noticeable symptoms. However, these cysts increase the risk of spontaneous pneumothorax, a collapsed lung that occurs when air leaks into the space between the lung and chest wall. Some people with Birt-Hogg-Dubé syndrome will experience at least one pneumothorax during their lifetime, often occurring in young adulthood. A collapsed lung typically causes sudden chest pain and breathlessness requiring urgent medical attention. Kidney manifestations may not produce symptoms initially, but some individuals develop kidney tumours that can eventually cause blood in the urine, flank pain or a palpable mass if tumours grow substantially before detection.
Video: Is cancer in your genes?
Affected organs
The skin is consistently affected in Birt-Hogg-Dubé syndrome, with fibrofolliculomas representing the hallmark feature. These benign hair follicle tumours reflect abnormal folliculin function in skin structures and are present in the vast majority of adults with the condition by their fourth or fifth decade. The lung tissue shows characteristic changes with multiple thin-walled cysts distributed throughout both lungs, predominantly in the lower and medial regions. These cysts represent areas where normal lung architecture has been replaced by air-filled spaces, creating structural weakness that predisposes to pneumothorax.
The kidneys are the organ system requiring closest clinical monitoring due to tumour risk. People with Birt-Hogg-Dubé syndrome have a substantially elevated likelihood of developing renal cell carcinoma compared with the general population. These kidney tumours can be bilateral and multifocal, and several different histological subtypes may occur, including chromophobe renal cell carcinoma and hybrid oncocytic tumours. Kidney tumours associated with the syndrome tend to grow relatively slowly but still require careful surveillance and intervention when indicated.
Risks & severity
The severity of Birt-Hogg-Dubé syndrome varies considerably between individuals. Some people may have only mild skin changes with no significant lung or kidney involvement, whilst others develop more extensive manifestations requiring active medical management. The skin lesions themselves are benign and pose no direct health risk, though their appearance can affect quality of life for some individuals. Lung cysts are generally asymptomatic unless they lead to pneumothorax, which can occur spontaneously, sometimes recurrently, and may require surgical intervention to prevent future episodes.
The most significant health concern relates to kidney tumour development. Evidence suggests that renal tumours in Birt-Hogg-Dubé syndrome typically begin to appear from the third decade onwards, with median age at diagnosis in the forties or fifties. These tumours can be aggressive if left undetected, making regular kidney surveillance crucial. However, with appropriate monitoring and timely intervention when tumours are identified, outcomes are generally favourable. The risk of developing renal cell carcinoma appears to increase with age, emphasising the importance of lifelong follow-up for individuals with a confirmed diagnosis.
Genetic causes
Birt-Hogg-Dubé syndrome results from pathogenic variants in FLCN, located on chromosome 17. This gene encodes folliculin, a protein that participates in several cellular processes including regulation of cell growth, energy metabolism and cellular signalling pathways. Folliculin appears to function as a tumour suppressor, meaning it normally helps prevent cells from growing and dividing too rapidly or in an uncontrolled manner. The protein interacts with other molecules in pathways that sense nutrient availability and control cell proliferation in response to environmental signals.
When a pathogenic variant disrupts FLCN function, cells lose this regulatory control, particularly in tissues that normally express high levels of folliculin such as skin, kidney and lung. This loss of normal growth regulation allows abnormal tissue development, leading to fibrofolliculomas in the skin, cyst formation in the lungs and increased susceptibility to kidney tumour formation. Most disease-causing variants in FLCN are predicted to result in a shortened, non-functional protein, though the precise mechanisms linking folliculin deficiency to the specific manifestations of the syndrome remain an active area of research. Different variants in FLCN can cause the full spectrum of features associated with Birt-Hogg-Dubé syndrome, and there is no strong correlation between specific genetic changes and disease severity.
- FLCN folliculinThe FLCN gene encodes the folliculin protein, which is thought to function as a tumour suppressor, playing roles in cell growth, division, and tissue repair.
Inheritance pattern
Birt-Hogg-Dubé syndrome follows an autosomal dominant inheritance pattern, meaning a pathogenic variant in just one copy of FLCN is sufficient to cause the condition. Each child of an affected parent has a 50 per cent chance of inheriting the altered gene. Both men and women can develop the condition and can pass it to children of either sex with equal probability. Families with Birt-Hogg-Dubé syndrome typically show multiple affected individuals across generations, though the specific features and their severity can differ markedly between family members carrying the same FLCN variant.
In some cases, an individual may be the first person in their family diagnosed with Birt-Hogg-Dubé syndrome, representing a de novo (new) pathogenic variant that arose spontaneously rather than being inherited from a parent. This appears to be relatively uncommon, with most cases showing clear family history when relatives are examined carefully for subtle features. Because features can be mild or overlooked, particularly skin changes that might be dismissed as cosmetically insignificant, comprehensive family history and examination of at-risk relatives is valuable when Birt-Hogg-Dubé syndrome is diagnosed. Genetic counselling can help families understand inheritance risks and facilitate discussions about predictive testing for relatives who may have inherited the familial variant.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of Birt-Hogg-Dubé syndrome typically combines clinical assessment with genetic testing. A clinical diagnosis may be suspected when characteristic fibrofolliculomas are identified, particularly if there is a family history of similar skin lesions, spontaneous pneumothorax or kidney tumours. Dermatological examination can identify the distinctive appearance and distribution of skin lesions, and a skin biopsy may confirm fibrofolliculomas histologically, though biopsy is not always necessary if clinical features are typical.
Definitive diagnosis relies on genetic testing to identify a pathogenic variant in FLCN. Within the NHS Genomic Medicine Service, testing for Birt-Hogg-Dubé syndrome falls under the cancer and unusual tumour genomics pathways, with the R207 code covering renal cancer genomic testing that may include FLCN analysis in appropriate clinical contexts. Referral to clinical genetics services typically occurs through renal oncology, respiratory medicine or dermatology when clinical features raise suspicion. Once a diagnosis is confirmed in an individual, predictive genetic testing can be offered to at-risk family members, usually coordinated through genetic counselling services to ensure informed decision-making. Imaging studies including chest CT to assess for lung cysts and renal imaging to establish baseline kidney appearance are generally performed once a diagnosis is established.
Management & lifestyle
Management of Birt-Hogg-Dubé syndrome focuses on surveillance for kidney tumours and addressing complications when they arise, rather than attempting to prevent the condition's manifestations. Regular kidney imaging, typically with MRI or CT scanning, forms the cornerstone of management, enabling early detection of renal tumours when they are small and most amenable to nephron-sparing surgical approaches. Evidence suggests that surveillance should begin by the age of 20 years in individuals with a confirmed diagnosis, with imaging intervals determined by findings and individual risk assessment, though commonly performed annually or every few years depending on whether tumours are present.
Skin lesions can be addressed for cosmetic reasons if desired, with options including laser therapy, cryotherapy or surgical removal, though lesions may recur and treatment is generally considered elective. For lung cysts, no specific preventive intervention is available, but individuals should be educated about recognising symptoms of pneumothorax and seeking urgent medical attention if sudden chest pain or breathlessness develops. Some specialists recommend avoiding activities that involve significant pressure changes, such as scuba diving or high-altitude aviation, though evidence for this recommendation is limited. If recurrent pneumothorax occurs, surgical procedures such as pleurodesis may be considered to reduce future risk. Smoking cessation is strongly advised, as smoking may compound lung-related risks.
NHS care for Birt-Hogg-Dubé syndrome typically involves coordinated input from clinical genetics, renal oncology, respiratory medicine and dermatology services. A personalised surveillance plan is developed based on individual features and family history, with genetic counselling supporting affected individuals and their relatives in understanding inheritance risks and making informed decisions about predictive testing. As understanding of the condition evolves, management approaches may be refined, making engagement with specialist services valuable for accessing current evidence-based care.
UK care pathway
Within the NHS Genomic Medicine Service, individuals with suspected Birt-Hogg-Dubé syndrome are typically referred to clinical genetics services, often following identification of characteristic features by renal specialists, respiratory physicians or dermatologists. Genetic testing for FLCN forms part of cancer genomics pathways, particularly the R207 panel covering renal cancer genomics when kidney tumours are present or there is strong family history. Once a pathogenic variant is confirmed, affected individuals enter structured surveillance programmes coordinated through specialist centres with expertise in cancer predisposition syndromes.
Genetic counsellors play a central role in supporting families affected by Birt-Hogg-Dubé syndrome, explaining inheritance patterns, discussing implications for relatives and facilitating predictive testing for family members who wish to know their genetic status. Surveillance protocols are individualised based on age, imaging findings and family history of aggressive kidney tumours, with multidisciplinary team input ensuring coordinated care across specialties. Access to psychological support and patient information resources is available through clinical genetics services, helping individuals and families adapt to living with a cancer predisposition syndrome and make informed decisions about their care.
Frequently asked questions
Will my children inherit Birt-Hogg-Dubé syndrome if I have it?
Each of your children has a 50 per cent chance of inheriting the FLCN variant that causes Birt-Hogg-Dubé syndrome. However, even if they inherit the genetic change, the features they develop and their severity can differ from yours. Genetic counselling can help you discuss testing options and implications for your family.
How often will I need kidney scans if I have Birt-Hogg-Dubé syndrome?
Kidney imaging frequency is individualised based on your age, whether any tumours are present and your family history. Many people have scans annually or every few years, with intervals adjusted based on findings. Your specialist team will recommend a surveillance schedule tailored to your situation.
Can the skin lesions in Birt-Hogg-Dubé syndrome be removed?
Fibrofolliculomas can be treated for cosmetic reasons using laser therapy, cryotherapy or surgical removal. However, these are benign growths that pose no health risk, so treatment is optional and based on personal preference. Lesions may recur after treatment, so discussing expectations with a dermatologist is helpful.
What should I do if I experience sudden chest pain?
Sudden chest pain, particularly if accompanied by breathlessness, could indicate a collapsed lung (pneumothorax), which is more common in people with Birt-Hogg-Dubé syndrome. You should seek urgent medical attention through NHS 111, your GP or A&E depending on severity, as pneumothorax requires prompt treatment.
Are kidney tumours in Birt-Hogg-Dubé syndrome always cancerous?
Most kidney tumours that develop in Birt-Hogg-Dubé syndrome are renal cell carcinomas, which are cancerous, though they often grow relatively slowly. Regular surveillance aims to detect tumours early when they are small and can be removed with kidney-preserving surgery. Not everyone with the condition will develop kidney tumours, but surveillance is important because risk is elevated.
References
- Adam MP, Bick S, Mirzaa GM. Birt-Hogg-Dubé Syndrome. 1993. PMID: 20301695
- Patel TM, Beal MA, Schroeder G. Birt-Hogg-Dubé Syndrome. Clinics in chest medicine. 2025. PMID: 41110925
- Gupta N, Sunwoo BY, Kotloff RM. Birt-Hogg-Dubé Syndrome. Clinics in chest medicine. 2016. PMID: 27514594
- Crane JS, Rutt V, Oakley AM. Birt-Hogg-Dube Syndrome. 2023. PMID: 28846260
- Daccord C, Good JM, Morren MA. Birt-Hogg-Dubé syndrome. European respiratory review : an official journal of the European Respiratory Society. 2020. PMID: 32943413
- Riegert-Johnson DL, Boardman LA, Hefferon T. Birt-Hogg-Dubé Syndrome. 2009. PMID: 21249760
- Ghosh S, Farver CF. Birt-Hogg-Dubé Syndrome. Radiology. 2022. PMID: 34846202
- Napolitano G, Di Malta C, Esposito A. A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dubé syndrome. Nature. 2020. PMID: 32612235