Birt-Hogg-Dubé (BHD) syndrome is a rare genetic disorder associated with mutations in the BHD gene, which can manifest symptoms at any age, including dermatological and pulmonary complications, as well as renal tumors. This study presents a case of a BHD patient who experienced spontaneous pneumothorax, aiming to enhance the understanding of this syndrome.

A 42-year-old female patient presented with left-sided chest pain and tightness lasting three days. Chest computed tomography scans revealed left-sided pneumothorax and multiple pulmonary bullae. Physical examination indicated decreased vocal fremitus and tympanic percussion on the left side. A thorough family history revealed a pattern of pulmonary disorders, including emphysema, spontaneous pneumothorax, and lung cancer among relatives. Genetic testing identified a heterozygous frameshift mutation in the FLCN gene at the 17p11.2 locus. Based on the clinical presentation, imaging findings, family history, and genetic results, the patient was suspected to have BHD syndrome.

We present a case of a heterozygous mutation in the FLCN gene in a patient with BHD syndrome, aiming to review the associated clinical characteristics and genetic mechanisms of this condition. This case serves as a reference point to offer insights into the diagnosis of multiple pulmonary cysts and spontaneous pneumothorax of unknown etiology in clinical practice.

• Birt-Hogg-Dubé syndrome
• Spontaneous pneumothorax
• Genetic disorder
• FLCN gene
• Folliculin
• Case report

• Pneumothorax
• Respiratory system
• Urinary and genital tract disorders

• Birt-Hogg-Dubé syndrome
• cohort study
• diffuse interstitial lung disease
• orphan pulmonary diseases
• pulmonary function test

• Interstitial lung disease
• Respiratory medicine

• Humans
• Birt-Hogg-Dube Syndrome/genetics
• Birt-Hogg-Dube Syndrome/diagnosis
• Pneumothorax/genetics
• Pneumothorax/diagnostic imaging
• Male
• Proto-Oncogene Proteins/genetics
• Tumor Suppressor Proteins/genetics
• Adult
• Tomography, X-Ray Computed
• Diagnosis, Differential
• Lung/diagnostic imaging
• Lung/pathology

• urological cancer
• genetic testing
• respiratory tract diseases

• Birt-Hogg-Dube Syndrome/diagnosis
• Birt-Hogg-Dube Syndrome/genetics
• Birt-Hogg-Dube Syndrome/therapy
• Humans
• Tumor Suppressor Proteins/genetics
• Proto-Oncogene Proteins/genetics
• Genetic Testing/standards
• Kidney Neoplasms/diagnosis
• Kidney Neoplasms/genetics
• Kidney Neoplasms/therapy
• Carcinoma, Renal Cell/genetics
• Carcinoma, Renal Cell/diagnosis
• Carcinoma, Renal Cell/therapy

• Imaging/CT MRI etc
• Lung Cancer
• Paediatric Lung Disaese
• Rare lung diseases

• Adolescent
• Adult
• Child
• Female
• Humans
• Male
• Middle Aged
• Young Adult
• Cysts/genetics
• Cysts/pathology
• Cysts/diagnostic imaging
• DEAD-box RNA Helicases/genetics
• Germ-Line Mutation
• Lung Diseases/genetics
• Lung Diseases/pathology
• Lung Diseases/diagnostic imaging
• Lung Diseases/epidemiology
• Lung Neoplasms/genetics
• Lung Neoplasms/pathology
• Lung Neoplasms/diagnostic imaging
• Prevalence
• Pulmonary Blastoma/genetics
• Pulmonary Blastoma/pathology
• Registries
• Ribonuclease III/genetics
• Tomography, X-Ray Computed
• United States/epidemiology
• Aged

• R01 CA143167 NCI NIH HHS
• R37 CA244940 NCI NIH HHS

• Rare lung diseases

• Humans
• Rare Diseases/diagnosis
• Rare Diseases/genetics
• Rare Diseases/complications
• Lung Diseases/etiology
• Lung Diseases, Interstitial/diagnosis
• Cysts/diagnosis
• Cysts/pathology
• United Kingdom
• Diagnosis, Differential

• Birt-Hogg-Dubé syndrome
• case report
• folliculin gene mutation
• pulmonary cystic disease
• renal tumor
• secondary spontaneous pneumothorax

• Birt-Hogg-Dubé syndrome
• DCLD
• Diagnostic algorithm
• FLCN
• Gene
• Sjogren’s syndrome

• Humans
• Birt-Hogg-Dube Syndrome/complications
• Birt-Hogg-Dube Syndrome/diagnosis
• Birt-Hogg-Dube Syndrome/pathology
• Sjogren's Syndrome/complications
• Sjogren's Syndrome/diagnosis
• Sjogren's Syndrome/pathology
• Lung Diseases/diagnosis
• Lung/pathology
• Cysts/pathology

• 81900002 to TG, 82070003 to HL National Natural Science Foundation of China
• 81900002 to TG, 82070003 to HL National Natural Science Foundation of China

• birt-hogg-dubé
• birt-hogg-dubé syndrome
• carcinomas renal cell
• cystic lesions of the lung
• renal tumors

• Birt–Hogg–Dubé syndrome
• FLCN
• Scuba diving
• arterial gas embolism
• barotrauma
• folliculin
• lung cysts
• spontaneous pneumothorax

• Humans
• Birt-Hogg-Dube Syndrome/diagnosis
• Birt-Hogg-Dube Syndrome/genetics
• Birt-Hogg-Dube Syndrome/complications
• Diving/adverse effects
• Tumor Suppressor Proteins/genetics
• Pneumothorax/genetics
• Lung Diseases/etiology
• Lung Injury
• Cysts/genetics
• Cysts/pathology
• Barotrauma/diagnosis
• Barotrauma/complications

• G0601840 Medical Research Council
• G1002610 Medical Research Council
• MR/R009120/1 Medical Research Council
• MR/V028669/1 Medical Research Council

• Birt-Hogg-Dubé (BHD) syndrome
• Computed tomography
• Folliculin gene mutation
• Pneumothorax
• Pulmonary cyst
• Pulmonary function test

• Amyloidosis
• Birt-Hogg-Dubé syndrome (BHD)
• Cystic lung disease
• Light chain deposition disease
• Lymphangioleiomyomatosis (LAM)
• Lymphoid interstitial pneumonia
• Pulmonary Langerhans cell histiocytosis (LCH)

• Humans
• Lymphangioleiomyomatosis/diagnosis
• Lymphangioleiomyomatosis/etiology
• Lymphangioleiomyomatosis/therapy
• Histiocytosis, Langerhans-Cell/complications
• Histiocytosis, Langerhans-Cell/diagnosis
• Histiocytosis, Langerhans-Cell/pathology
• Birt-Hogg-Dube Syndrome/complications
• Birt-Hogg-Dube Syndrome/diagnosis
• Birt-Hogg-Dube Syndrome/pathology
• Tomography, X-Ray Computed/methods
• Lung Diseases/diagnosis
• Lung Diseases/etiology
• Lung/pathology
• Cysts/diagnosis
• Cysts/complications
• Cysts/pathology
• Diagnosis, Differential

• R01 HL157424 NHLBI NIH HHS

• airway epithelium
• emphysema
• rare lung diseases
• tobacco and the lung

• Animals
• Humans
• Mice
• Cigarette Smoking/adverse effects
• Lung/chemistry
• Lung/metabolism
• Proto-Oncogene Proteins/analysis
• Proto-Oncogene Proteins/genetics
• Proto-Oncogene Proteins/metabolism
• Pulmonary Disease, Chronic Obstructive/genetics
• Pulmonary Disease, Chronic Obstructive/metabolism
• Tumor Suppressor Proteins/analysis
• Tumor Suppressor Proteins/genetics
• Tumor Suppressor Proteins/metabolism
• Ubiquitins/metabolism

• I01 CX000105 CSRD VA
• I01 CX001048 CSRD VA
• R01 GM132127 NIGMS NIH HHS
• R01 HL149719 NHLBI NIH HHS
• American Heart Association
• National Heart, Lung, and Blood Institute
• National Institute of General Medical Sciences
• U.S. Department of Veterans Affairs

• Genes, Tumor Suppressor
• Pathology, Molecular
• RNA
• Tumor Suppressor Proteins/genetics
• Virulence
• Humans

• Birt–Hogg–Dube syndrome
• FLCN mutation
• chest computed tomography
• cystic lung disease

• Birt‐Hogg‐Dubé syndrome
• fibrofolliculomas
• pneumothorax
• renal cancer

• Humans
• Birt-Hogg-Dube Syndrome/diagnosis
• Birt-Hogg-Dube Syndrome/genetics
• Birt-Hogg-Dube Syndrome/complications
• Pneumothorax/complications
• Pneumothorax/diagnosis
• Pneumothorax/genetics
• TOR Serine-Threonine Kinases/genetics
• Skin/pathology
• Mutation
• Skin Neoplasms/pathology
• Sirolimus

Spontaneous pneumothorax is a common manifestation of Birt–Hogg–Dubé (BHD) syndrome, an inherited disorder caused by mutation of the folliculin (FLCN) gene. A 44-year-old female with a history of breast cancer was diagnosed with recurrent pneumothorax. Chest CT showed multiple cysts with left lung pneumothorax, and she received surgery for the diagnosis. Because the patient also had a family history of spontaneous pneumothorax, a FLCN genetic examination was conducted. A novel heterozygous, likely pathogenic variant (NM_144997.5:c.779+2T > C) was detected in the proband, her mother, and aunt. This is the first report of a new mutation of FLCN gene in a BHD syndrome patient.

• BHD syndrome, Birt–Hogg–Dubé syndrome
• Birt–Hogg–Dubé syndrome
• Cystic lung disease
• FLCN gene
• FLCN gene, folliculin gene
• Genetic study
• LAM, lymphangioleiomyomatosis
• Pneumothorax

Introduction: The presence of intra-pulmonary air lesions such as cysts, blebs and emphysema bullae, predisposes to pulmonary barotrauma during pressure variations, especially during underwater diving activities. These rare accidents can have dramatic consequences. Chest radiography has long been the baseline examination for the detection of respiratory pathologies in occupational medicine. It has been replaced since 2018 by the thoracic CT scan for military diving fitness in France. The objective of this work was to evaluate the prevalence of the pulmonary abnormalities of the thoracic CT scan, and to relate them to the characteristics of this population and the results of the spirometry.

Methods: 330 records of military diving candidates who underwent an initial assessment between October 2018 and March 2021 were analyzed, in a single-center retrospective analysis. The following data were collected: sex, age, BMI, history of respiratory pathologies and smoking, treatments, allergies, diving practice, results of spirometry, reports of thoracic CT scans, as well as fitness decision.

Results: The study included 307 candidates, mostly male, with a median age of 25 years. 19% of the subjects had abnormal spirometry. We identified 25% of divers with CT scan abnormalities. 76% of the abnormal scans were benign nodules, 26% of which measured 6 mm or more. Abnormalities with an aerial component accounted for 13% of the abnormal scans with six emphysema bullae, three bronchial dilatations and one cystic lesion. No association was found between the presence of nodules and the general characteristics of the population, whereas in six subjects emphysema bullae were found statistically associated with active smoking or abnormal spirometry results.

Conclusion: The systematic performance of thoracic CT scan in a young population free of pulmonary pathology revealed a majority of benign nodules. Abnormalities with an aerial component are much less frequent, but their presence generally leads to a decision of unfitness. These results argue in favor of a systematic screening of aeric pleuro-pulmonary lesions during the initial assessment for professional divers.

• birt-hogg-dubé syndrome
• rare genetic disorder
• renal cell carcinoma (rcc)
• tumor imaging
• tumor suppressor gene

A 9‐week‐old male intact Cavalier King Charles Spaniel was presented for evaluation of acute onset dyspnea caused by left‐sided pneumothorax. Thoracic computed tomography (CT) identified multiple pulmonary bullae and blebs in multiple lung lobes. Rupture of ≥1 pulmonary blebs or bullae, precipitated by low impact trauma, was the suspected cause of pneumothorax. A volume of 7.5 mL/kg of fresh whole blood was collected from a type‐matched donor dog and administered into the left pleural space using a thoracostomy tube. The pneumothorax was successfully resolved and no adverse effects of blood patch pleurodesis were noted. The dog was clinically normal 12 months later.

• lung
• pleural space disease
• pneumothorax
• respiratory

In this comment, we highlight the diagnosis of Birt–Hogg–Dubé (BHD) in a 60-year-old man was made from identification and removal of normochromic papular cutaneous lesions whose histological examination indicated trichodyscomas and which are considered equivalent to fibrofolliculomas, presence of bilateral renal mass suggestive of angiomyolipomas by imaging exams. A benign/likely benign variant of FLCN in the intron 13 was also detected. Still, his previous pathological history presented other relevant data such as the prior removal of vocal cord angioma, total thyroidectomy, and left parotidectomy due to a cystic lesion whose histopathological examination revealed the presence of oncocytoma and lipomatosis, in addition to basal cell cutaneous carcinoma. Simultaneous gastrointestinal hyperplastic polyposis was found in this patient. The case we reported does not have the genotypic and phenotypic expressions most present in BHDS. These facts make it important for readers to know the clinical and genetic presentation facets of this unusual syndrome.

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant inherited disorder caused by germline mutations in folliculin (FLCN). Despite our significantly evolved understanding of BHD over the past decades, no bibliometric analyses have been conducted in this field. This study aimed to analyze and visualize the characteristics of publication outputs, the research hotspots, and scientific frontiers about BHD using bibliometric analysis.

All relevant literature on BHD was culled from the Web of Science Core Collection (WoSCC) database. Valid data were extracted from the articles and visually analyzed using CiteSpace and VOSviewer.

A total of 751 qualifying papers were included. Publication outputs concerning BHD increased over time. The dominant position of the United States and Japan in BHD research field was evident. National Cancer Institute (the USA) and Yokohama City University (Japan) were the two most productive organizations. W. Marston Linehan exerted a considerable publication impact and had made the most remarkable contributions in the field of BHD. Plos One was the journal with the highest publication outputs, and half of the top 10 journals and co-cited journals belonged to Q1 or Q2. Keyword citation bursts revealed that management, tumor suppressor, flcn gene, spectrum, diagnosis, risk, computed tomography were the emerging research hotspots.

Research on BHD is prosperous. International cooperation between countries and organizations is also expected to deepen and strengthen in the future. Our results indicated that FLCN-associated pathways involved in the pathogenesis of BHD, specific options for early diagnosis, and molecular-targeting therapies will remain research hotspots in the future.

Birt–Hogg–Dubé syndrome (BHDS) is a rare, autosomal dominant, inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterised by skin lesions (fibrofolliculomas, trichodiscomas, acrochordons), pulmonary cysts with pneumothoraces and renal tumours. We present the features of Polish patients with BHDS.

The first case of BHDS in Poland was diagnosed in 2016. Since then, 15 cases from 10 families have been identified. Thirteen patients were confirmed via direct FLCN sequencing, and two according to their characteristic clinical and radiological presentations.

BHDS was diagnosed in 15 cases (13 women and 2 men) from 10 families. The mean ages at the time of first pneumothorax and diagnosis were 38.4 ± 13.9 and 47.7 ± 13 years, respectively. Five patients (33%) were ex-smokers (2.1 ± 1.37 packyears), and 10 (67%) had never smoked cigarettes. Twelve patients (83%) had a history of recurrent symptomatic pneumothorax. Three patients had small, asymptomatic pneumothoraces, which were only detected upon computed tomography examination. All patients had multiple bilateral pulmonary cysts, distributed predominantly in the lower and middle, peripheral, and subpleural regions of the lungs. Generally, patients exhibited preserved lung function. Skin lesions were seen in four patients (27%), one patient had renal angiomyolipoma, and one had bilateral renal cancer. Different mutations of the FLCN gene were identified (mainly in exon 6), with two novel heterozygous variants: c.490delA p.(Arg164GlyTer13) and c.40delC p.(His14ThrsfTer41).

All analysed patients with BHDS presented with lung lesions and with less frequent skin and renal lesions than previously reported in other populations. In addition, more frequent mutations located in exon 6 were detected, and two novel FLCN gene mutations were identified.

The online version contains supplementary material available at 10.1186/s13023-021-01931-0.

• Birt–Hogg–Dubé syndrome
• Hereditary leiomyomatosis and renal cell carcinoma syndrome
• Hereditary renal tumor syndrome
• Tuberous sclerosis complex
• Von Hippel–Lindau disease

Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant disease that has been characterized by skin lesions, multiple pulmonary cysts, spontaneous pneumothorax, and renal tumors, but the patients in Asian countries may show fewer symptoms. We aimed to explore and summarize the clinical features of BHD patients in East Asia to facilitate early diagnosis and timely interventions.

We collected and analyzed the clinical data of patients diagnosed with BHD in our hospital by reviewing medical records. We performed a systematic literature search regarding the presenting clinical features in BHD patients from China, Japan, and Korea and then reviewed the publications that were identified.

In our hospital, 10 patients were diagnosed with BHD from April 2015 to September 2019. After reviewing the literature, we recruited 38 articles, including 12, 20, and 6 reports from China, Japan, and Korea, respectively. A total of 166 patients were included in this study, and 100 of them (60.2%) were females. Multiple pulmonary cysts were present in 145 patients (87.3%), and 124 patients (74.7%) had a history of pneumothorax on at least one occasion. Skin biopsy confirmed fibrofolliculomas (FFs) alone in 22 patients (13.3%), trichodiscomas (TDs) alone in 3 patients (1.8%), and both FFs and TDs in 7 patients (4.2%). Renal carcinoma only occurred in 12 (7.2%) patients. The most frequent genetic mutations in East Asian patients were c.1285delC on exon 11 (18.4%), c.1285dupC on exon 11 (18.4%), and c.1347_1353dupCCACCCT on exon 12 (8.2%).

Our findings suggested that pulmonary cysts are the most frequent radiological findings, and pneumothorax is the most common symptom in East Asian patients with BHD, and that skin lesions and kidney involvement are less frequent. To make an early diagnosis and minimize the severity of complications, careful observation, and timely genetic examination of the FLCN gene is essential.

• Birt-Hogg-Dube syndrome (BHD syndrome)
• East Asia
• pneumothorax
• pulmonary cysts

Birt–Hogg–Dubé syndrome (BHD) is a rare inherited autosomal dominant disorder caused by germline mutations in the tumour suppressor gene FLCN, encoding the protein folliculin. Its clinical expression typically includes multiple pulmonary cysts, recurrent spontaneous pneumothoraces, cutaneous fibrofolliculomas and renal tumours of various histological types. BHD has no sex predilection and tends to manifest in the third or fourth decade of life. Multiple bilateral pulmonary cysts are found on chest computed tomography in >80% of patients and more than half experience one or more episodes of pneumothorax. A family history of pneumothorax is an important clue, which suggests the diagnosis of BHD. Unlike other cystic lung diseases such as lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis, BHD does not lead to progressive loss of lung function and chronic respiratory insufficiency. Renal tumours affect about 30% of patients during their lifetime, and can be multiple and recurrent. The diagnosis of BHD is based on a combination of genetic, clinical and/or skin histopathological criteria. Management mainly consists of early pleurodesis in the case of pneumothorax, periodic renal imaging for tumour detection, and diagnostic work-up in search of BHD in relatives of the index patient.

Birt–Hogg–Dubé syndrome is a rare genetic disorder characterised by multiple lung cysts, recurrent pneumothoraces, skin lesions and kidney tumours. As the presenting symptoms may be respiratory, chest physicians should be able to identify this disease.https://bit.ly/2xsOTuk

Diffuse cystic lung diseases include a group of heterogeneous disorders characterised by the presence of cysts within the lung parenchyma, sometimes showing a characteristic computed tomography scan pattern that allows diagnosis. The pathogenetic mechanisms underlying cyst formation in the lung are still not clear and a number of hypotheses have been postulated according to the different aetiologies: ball-valve effect, ischaemic dilatation of small airways and alveoli related to infiltration and obstruction of small vessels and capillaries that supply the terminal bronchioles and connective tissue degradation by matrix metalloproteases. A wide number of lung cyst diseases have been classified into six diagnostic groups according to the aetiology: neoplastic, congenital/genetic, lymphoproliferative, infective, associated with interstitial lung diseases, and other causes. This article focuses on lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and Erdheim–Chester disease, Birt–Hogg–Dubé, follicular bronchiolitis and lymphocytic interstitial pneumonia, light-chain deposition disease and amyloidosis, congenital lung disease associated with aberrant lung development and growth, and cystic lung disease associated with neoplastic lesion. These cystic diseases are epidemiologically considered as ultra-rare conditions as they affect fewer than one individual per 50 000 or fewer than 20 individuals per million. Despite the rarity of this group of disorders, the increasing use of high-resolution computed tomography has improved the diagnostic yield, even in asymptomatic patients allowing prompt and correct therapy and management without the need for a biopsy.

Diffuse cystic lung diseases show a characteristic CT scan pattern that often allows for diagnosis, even in asymptomatic patients, allowing prompt correct therapy and management without the needing of a biopsyhttps://bit.ly/2wIUKet

• Marfan syndrome (MFS)
• bulla
• elastic fibers
• pneumothorax

Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal-dominant inherited disease. Typical clinical features include skin lesions, pulmonary cysts, and renal tumors. However, the syndrome remains to be underdiagnosed as a result of its heterogeneous clinical manifestation. In this report, we present the case of a 75-year-old male patient who was referred to the emergency department with pneumothorax, leading to the diagnosis of BHDS. Based on characteristic morphologic features, radiologists have the opportunity to propose BHDS as a differential diagnosis. Establishing the diagnosis in a timely manner is crucial, as these patients require lifelong screening examinations for renal cancer.

• Appendicealdiverticulosis
• Birt-Hogg-Dubé syndrome
• Chromophoberenal cell carcinoma
• Computed tomography
• Pneumothorax

• Birt–Hogg–Dubé syndrome
• cystic lung disease
• familial cancer syndrome
• paediatric lung disease
• pneumothorax

The purpose of this study was to create a practical CT-based algorithm to differentiate Birt-Hogg-Dubé (BHD) syndrome from other diffuse cystic lung diseases (DCLD).

The study was a retrospective review of the CT images of 33 patients with BHD syndrome, 33 patients with LAM, and 23 patients with NBNL (non-BHD and non-LAM) among DCLD patients. On the basis of the data collected, the CT images were reviewed again to evaluate the characteristics (size, number, distribution, and morphology) of pulmonary cysts.

Lower lung-predominant cysts were more likely to be found in patients with BHD syndrome than in patients with LAM or in the NBNL DCLD group. In the axial distribution, 18 of 33 patients in BHD group had cysts that were predominantly near the mediastinum, and all the patients in the LAM and NBNL DCLD groups had diffuse cysts. The appearance of fusiform cysts was more easily observed in patients in the BHD group. In total, 58% patients in the BHD group had less than 50 lung cysts, while all patients in the non-BHD group had more than 50 lung cysts. The biggest cyst was located in the lower lobe in 28 of 33 patients in the BHD group, while 11 of 33 patients in LAM group and 10 patients in the NBNL DCLD group had the biggest cyst in the lower lobe.

The pulmonary cysts in patients with BHD tended to be fusiform, less numerous and located predominantly in the lower lobe and near the mediastinum. These radiologic pulmonary features could assist physicians in differentiating BHD from other DCLDs.

• Birt-Hogg-Dubé syndrome
• Diffuse cystic lung diseases
• FLCN
• Image
• Radiology

The cystic lung diseases are rare orphan lung disorders that most physicians will see infrequently in their everyday practice. Diagnostic and treatment options have improved over recent decades, with opportunities for slowing rate of progression and improving outcome for patients. This review provides a summary of the clinical approach to these lung disorders, including how to differentiate between different imaging patterns, clinical features, differential diagnosis and characteristics of the commonest presenting disorders.

Cystic lung diseases are uncommon disorders with a wide differential diagnosis. Treatment has improved over the last decade and respiratory physicians should feel encouraged to investigate such cases thoroughly to reach a final diagnosis.https://bit.ly/2W6Is9D

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the FLCN gene coding for folliculin. Its clinical expression includes cutaneous fibrofolliculomas, renal tumors, multiple pulmonary cysts, and recurrent spontaneous pneumothoraces. Data on lung function in BHD are scarce and it is not known whether lung function declines over time. We retrospectively assessed lung function at baseline and during follow-up in 96 patients with BHD.

Ninety-five percent of BHD patients had multiple pulmonary cysts on computed tomography and 59% had experienced at least one pneumothorax. Mean values of forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), FEV₁/FVC ratio, and total lung capacity were normal at baseline. Mean (standard deviation) residual volume (RV) was moderately increased to 116 (36) %pred at baseline, and RV was elevated > 120%pred in 41% of cases. Mean (standard deviation) carbon monoxide transfer factor (DLco) was moderately decreased to 85 (18) %pred at baseline, and DLco was decreased < 80%pred in 33% of cases. When adjusted for age, gender, smoking and history of pleurodesis, lung function parameters did not significantly decline over a follow-up period of 6 years.

Cystic lung disease in BHD does not affect respiratory function at baseline except for slightly increased RV and reduced DLco. No significant deterioration of lung function occurs in BHD over a follow-up period of 6 years.

• Birt-Hogg-Dube syndrome
• FLCN protein, human
• Pleurodesis
• Respiratory function tests

Birt‐Hogg‐Dubé (BHD) syndrome is associated with the development of hereditary renal cell carcinoma (RCC) and is caused by a germline mutation in the folliculin gene. Most cases of BHD syndrome‐associated RCC (BHD‐RCC) are less aggressive than sporadic clear cell RCC and multifocal. Therefore, it is critical to distinguish BHD‐RCC from its sporadic counterparts to identify and monitor affected families and to preserve renal function for as long as possible. The World Health Organization/International Society of Urological Pathology consensus classification defined distinct entities for certain hereditary RCC; however, BHD‐RCC was not included in this classification. Although the clinical features and molecular mechanisms of BHD‐RCC have been investigated intensively over the last two decades, pathologists and urologists occasionally face difficulties in the diagnosis of BHD‐RCC that require genetic testing. Affected patients usually have miscellaneous benign disorders that often precede renal carcinogenesis. In the present review, we summarize the current understanding of the histopathological features of BHD‐RCC based on our epidemiological studies of Japanese families and a literature review. Pathological diagnostic clues and differential diagnosis of BHD‐RCC from other hereditary RCC are also briefly discussed.

• Birt-Hogg-Dubé syndrome
• folliculin
• hereditary cancer
• histopathology
• renal cell carcinoma

Birt-Hogg-Dubé syndrome (BHDS) is a rare, genetic, autosomal dominant disease caused by mutation in a folliculin gene. This syndrome is characterised by three main symptoms: benign lesions originating from hair follicles, variously shaped cysts in the lungs, and various types of benign and malignant kidney neoplasms. In our article we are going to present cases of two sisters with BHDS. In the case of the first sister skin lesions were accompanied by lung abnormalities. The second sister, however, presented with recurrent pneumothoraces associated with variously shaped lung cysts located mainly below the tracheal carina. In both instance diagnosis was confirmed by genetic test.

• Birt-Hogg-Dubé syndrome
• cystic lung diseases
• pneumothorax
• recurrent pneumothoraces

• gene
• Birt-Hogg-Dubé syndrome
• familial spontaneous pneumothorax
• genetics
• pneumothorax

• Birt-Hogg-Dube Syndrome/genetics
• Genetic Predisposition to Disease
• Genetic Testing
• Humans
• Mutation
• Pedigree
• Pneumothorax/genetics
• Proto-Oncogene Proteins/genetics
• Tumor Suppressor Proteins/genetics

• G1002610 Medical Research Council
• R01 HL118455 NHLBI NIH HHS
• MR/R009120/1 Medical Research Council
• R01 DK102146 NIDDK NIH HHS
• G0601840 Medical Research Council
• U01 HL131022 NHLBI NIH HHS
• R01 HL130974 NHLBI NIH HHS
• P01 HL132825 NHLBI NIH HHS
• R01 HL123546 NHLBI NIH HHS

• Air travel
• Incidence
• Lymphangioleiomyomatosis
• Pleurodesis
• Pneumothorax