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

• Clinical Epidemiology
• Pleural Disease

• Connective tissue disease associated lung disease
• Drug induced Lung Disease

• Humans
• Fluoroquinolones/adverse effects
• Male
• Pneumothorax/chemically induced
• Pneumothorax/epidemiology
• Adult
• Female
• Case-Control Studies
• Middle Aged
• France/epidemiology
• Anti-Bacterial Agents/adverse effects
• Risk Factors
• Databases, Factual

• French Medicines Agency (ANSM)

• aneurysm
• cardiomyopathy
• dissection
• heritable thoracic aortic disease
• vascular Ehlers-Danlos syndrome

• Circulating immune cells
• Mendelian randomization (MR)
• spontaneous pneumothorax (SP)

• cannabis-associated pneumothorax
• cardiothoracic surgery
• effects of cannabis use
• general internal medicine
• marijuana and pneumothorax
• pneumothorax
• primary spontaneous pneumothorax
• spontaneous pneumothorax
• tobacco vs cannabis

• Amyotrophy
• Case report
• Deoxyguanosine kinase deficiency
• Mitochondrial DNA depletion syndrome
• Mitochondriopathy
• Recurrent spontaneous pneumothorax

• Male
• Humans
• Child
• Pneumothorax/diagnostic imaging
• Pneumothorax/etiology
• Phosphotransferases (Alcohol Group Acceptor)
• Mitochondrial Diseases
• Liver

• Autologous blood
• polyglycolic acid sheet (PGA sheet)
• primary spontaneous pneumothorax (PSP)
• recurrence
• video-assisted thoracoscopic surgery (VATS)

• Dyspnea
• Dyspnée
• Ehlers-Danlos syndrome
• Fonction respiratoire
• Pneumothorax
• Pulmonary function
• Respiration
• Respiratory
• Syndromes d’Ehlers-Danlos

• Ehlers-Danlos syndrome
• complications
• extracutaneous
• heritable connective tissue disorders (HCTD)
• joint hypermobility

• Familial thoracic aortic aneurysm and dissection
• Loeys-dietz syndrome
• Marfan syndrome
• Thoracic aortic aneurysm

• adolescent health
• physiology
• therapeutics

• Adolescent
• Child
• Family
• Humans
• Length of Stay
• Pneumothorax/diagnosis
• Pneumothorax/therapy
• Recurrence
• Referral and Consultation
• Retrospective Studies

Sporadic lymphangioleiomyomatosis (S-LAM) is a rare neoplasm with heterogeneous clinical features that is conventionally considered to be related to TSC2. This study serves to elucidate the mutation landscape and potential correlation between S-LAM genomic profiles and clinical phenotypes.

Genomic profiles of 22 S-LAM patients were obtained by sequencing genomic DNA and cell-free DNA from various specimens using an NGS (next-generation sequencing)-based tumor-driver gene panel. Detected mutations were summarized. Symptoms, serum vascular endothelial growth factor D (VEGF-D) values, pulmonary function, and six-minute walk distance (6MWD) were compared among groups with different TSC2 status and genotypes to analyze genotype–phenotype correlations.

67 Variants in 43 genes were detected, with a TSC2 mutation detection rate of 68.2%. The TSC2 detection rate was similar in specimens obtained either through transbronchial lung biopsy (TBLB) or surgical lung biopsy (70.0% vs. 69.2%, p > 0.05). A novel mutation in VEZF1 (c.A659G) was detected in four participants and may represent a mild disease state. TSC2 mutation was significantly related to a shorter 6MWD (p < 0.05), and a higher percentage of VEGF-D over 800 pg/mL (p < 0.05); stop-gain mutation was significantly related to a higher prevalence of pneumothorax.

Tumor-driver mutations in genes other than TSC2 may have a role in S-LAM, and TBLB specimens are practical alternatives for genomic analysis. TSC2 mutation detectability and types are related to the disease severity and phenotypes of S-LAM.

The online version contains supplementary material available at 10.1186/s12890-022-02154-0.

The thoracic district is the most frequent visceral location of synovial sarcoma, generally involving lung and pleura as a large solid mass. We present herein a 57-year-old man with recurrent pneumothorax and a localized bulla at the lingula. The lesion was excised by a Video-Assisted-Thoracoscopic-Surgery (VATS) wedge resection and surprisingly consisted of a unilocular cyst with fibrous wall intermingled by a longitudinal proliferation of bland-looking, dense, monomorphic spindle cells diffusely expressing EMA, CD99, CD56 and focally staining with cytokeratins. Fluorescent in situ hybridization demonstrated the presence of SYT rearrangement and a diagnosis of pulmonary cystic monophasic synovial sarcoma was made. Only few similar cases have been reported in literature, mainly occurring in young male adults. A meticulous examination of all resected tissue from pneumothorax is the prerequisite to suspect this extremely challenging condition, while immuno-molecular studies are mandatory to achieve the correct diagnosis.

• adverse drug reaction
• adverse event
• levofloxacin
• piperacillin/tazobactam
• pneumothorax

The beta-coronavirus discovered in Wuhan in 2019 (COVID-19) provokes a series of affections from mild symptoms to life-threatening complications. There is evidence that associates the disease to spontaneous pneumothorax, however, the mechanism is unknown. The patient was a 45-year-old male with previous pneumonia due to COVID-19 who was attended the emergency department, where chest radiography was taken, confirming the diagnosis of right pneumothorax. However, the patient developed a new episode of pleuritic pain three days later, and a new radiograph showed left pneumothorax requiring a new chest tube. The simple tomography shows intraparenchymal bullae in the apical region of both lungs. The patient was kept under observation, and when improving, both endopleural chest drains were removed, and the patient was discharged. Spontaneous bilateral pneumothorax is a rare and potentially life-threatening complication. Identifying pulmonary bullae in patients with COVID-19 could be an early sign for these patients to develop spontaneous pneumothorax.

• Ataxia telangiectasia
• B lymphocytes
• T lymphocytes
• genotype
• lymphopenia
• primary immunodeficiency

• Ataxia Telangiectasia/diagnosis
• Ataxia Telangiectasia/genetics
• Ataxia Telangiectasia Mutated Proteins/genetics
• Humans
• Lymphopenia
• Mutation/genetics
• Retrospective Studies
• T-Lymphocytes

Birt-Hogg-Dubé syndrome (BHDS) is a rare monogenic condition mostly associated with germline mutations at FLCN. It is characterized by either one or more manifestations of primary spontaneous pneumothorax (PSP), skin fibrofolliculomas and renal carcinoma (chromophobe). Here, we comprehensively studied the mutational background of 31 clinically diagnosed BHDS patients and their 74 asymptomatic related members from 15 Indian families.

Targeted amplicon next-generation sequencing (NGS) and Sanger sequencing of FLCN in patients and asymptomatic members revealed a total of 76 variants. Among these variants, six different types of pathogenic FLCN mutations were detected in 26 patients and some asymptomatic family members. Two of the variants were novel mutations: an 11-nucleotide deletion (c.1150_1160delGTCCAGTCAGC) and a splice acceptor mutation (c.1301-1G > A). Two variants were Clinvar reported pathogenic mutations: a stop-gain (c.634C > T) and a 4-nucleotide duplication (c.1329_1332dupAGCC). Two known variants were: hotspot deletion (c.1285delC) and a splice donor mutation (c.1300 + 1G > A). FLCN mutations could not be detected in patients and asymptomatic members from 5 families. All these mutations greatly affected the protein stability and FLCN-FNIP2 interaction as observed by molecular docking method. Family-based association study inferred pathogenic FLCN mutations are significantly associated with BHDS.

Six pathogenic FLCN mutations were detected in patients from 10 families out of 15 families in the cohort. Therefore, genetic screening is necessary to validate the clinical diagnosis. The pathogenic mutations at FLCN affects the protein–protein interaction, which plays key roles in various metabolic pathways. Since, pathogenic mutations could not be detected in exonic regions of FLCN in 5 families, whole genome sequencing is necessary to detect all mutations at FLCN and/or any undescribed gene/s that may also be implicated in BHDS.

The online version contains supplementary material available at 10.1186/s13023-022-02326-5.

• BHDS
• FLCN mutations
• Family-based association
• Indian patients
• Molecular docking
• Primary spontaneous pneumothorax

• Col5a1
• Ehlers-Danlos
• collagen
• pediatrics
• respiratory mechanics

• Animals
• Collagen/genetics
• Collagen Type V/genetics
• Disease Models, Animal
• Ehlers-Danlos Syndrome/genetics
• Ehlers-Danlos Syndrome/pathology
• Female
• Haploinsufficiency
• Humans
• Lung/pathology
• Male
• Mice
• Mutation

• P20 GM125503 NIGMS NIH HHS
• U54 TR001629 NCATS NIH HHS
• Ehlers‐Danlos Society
• University of Arkansas for Medical Sciences
• National Institute of General Medical Sciences
• National Center for Advancing Translational Sciences

• Pneumothorax
• emphysema
• radiology
• recurrence
• thoracic surgical procedures

• Ehlers-Danlos syndromes
• hypermobility spectrum disorders
• pulmonary function
• respiratory

• Case-Control Studies
• Cross-Sectional Studies
• Ehlers-Danlos Syndrome/complications
• Ehlers-Danlos Syndrome/diagnosis
• Humans
• Joint Instability
• Spinal Diseases

• UL1 TR002014 NIH HHS

• ECM
• LDS
• LOX
• MFS
• TAAD

Familial spontaneous pneumothorax (FSP) accounts for 10% of primary spontaneous pneumothoraces. Appropriate investigation of FSP enables early diagnosis of serious monogenic diseases and the practice of precision medicine. Here, we show that a pneumothorax genetics multidisciplinary team (MDT) can efficiently diagnose a range of syndromic causes of FSP. A sizeable group (73.6%) of clinically unclassifiable FSPs remains. Using whole genome sequencing we demonstrate that most of these cases are not known monogenic disorders. Therefore, clinico-radiological assessment by an MDT has high sensitivity for currently known clinically important monogenic causes of FSP, which has relevance for the design of efficient pneumothorax services.

• pleural disease

• adolescent
• chest tube
• evidence‐based
• needle thoracostomy
• spontaneous pneumothorax
• tube thoracostomy

• Bayes theorem
• Birt-Hogg-Dube syndrome
• epidemiology
• gender
• meta-analysis
• pneumothorax
• prevalence

Gene-environment interactions are relevant for several respiratory diseases. This communication raises the hypothesis that the severity of COVID-19, a complex disease where the individual response to the infection may play a significant role, could partly result from a gene-environment interaction between air-pollution and Alpha-1 Antitrypsin (AAT) genes.

To evaluate the impact of the AAT and air pollution interaction on COVID-19, we introduced an AAT*air pollution global risk score summing together, in each country, an air pollution score (ozone, nitrogen dioxide and fine particulate matter) and an AAT score (which sums the ranked frequency of MZ, SZ, MS). We compared this global score with the ranking of European countries in terms of death number per million persons.

The ranking of the AAT*air pollution global risk score matched the ranking of the countries in terms of the observed COVID-19 deaths per 1M inhabitants, namely in the case of the first European countries: Belgium, UK, Spain, Italy, Sweden, France. We observed parallelism between the number of COVID deaths and the AAT*air pollution global risk in Europe. AAT anti-protease, immune-modulating and coagulation-modulating activities may explain this finding, although very speculatively.

Even if further studies taking into account genetic background, population density, temporal dynamics of individual epidemics, access to healthcare, social disparities and immunological response to SARS-CoV2 are needed, our preliminary observation urges to open a discussion on gene-environment interactions in COVID-19.

• AAT
• COVID-19
• air pollution
• environment

• Pneumothorax
• Spontaneous

•

Pediatric spontaneous pneumothorax is relatively a rare condition.

Pediatric primary spontaneous pneumothorax (PSP) is defined as the presence of air in the pleural cavity without underlying lung disease or thoracic trauma. Metachronous recurrence of PSP whether ipsilateral or contralateral is rare. Apical bullae and sub-pleural blebs are found in the majority of PSP patients. As in adults, surgery is indicated in cases with prolonged air leak. Video-assisted thoracoscopic surgery (VATS) is increasingly performed in children and has been reported to be both safe and effective.

An 11-years-old girl had bilateral attacks of PSP, the second attack happened one after the first one and this later was associated with her menarche. Chest CT scan detected bilateral apical blebs.

Contralateral recurrence in pediatric PSP is a low probability. The decision for surgery in the pediatric age group is a matter of controversy as there are no strict pediatric guidelines for management of PSP. Currently, VATS is superior to open surgery. Pediatric Catamenial pneumothorax is not well described in the literature.

Contralateral recurrence of PSP in children is rarer. No guidelines exist for the management of these cases. The association of pediatric PSP with menarche is not well described in the current literature.

• Management
• Metachronous recurrence
• Pediatric spontaneous pneumothorax
• VATS blebectomy

• DNA/RNA technologies
• genetics/genome-wide association studies
• immunology and immunodeficiency
• interstitial lung disease
• pulmonary vascular disorders

• bronchiectasis and primary ciliary dyskinesia
• cystic fibrosis (CF)
• genetics/Genome-Wide Association Studies (GWAS)
• immunology and immunodeficiency
• surfactant biology and pathophysiology

• Behavior Therapy
• Counseling
• Humans
• Pneumothorax

The Birt–Hogg–Dubé syndrome is an orphan genetic disease characterized by the development of renal neoplasms, fibrofolliculomas, pulmonary cysts and spontaneous pneumothoraces. Here, we report on the case of a 21-year-old man presenting with a primary event of a persistent spontaneous pneumothorax. Computed tomography images and a positive family history for pneumothoraces led to the suspicion of Birt–Hogg–Dubé syndrome. Genetic testing then confirmed the suspected clinical diagnosis, however with a mutation that has not yet been reported.

• Birt–Hogg–Dubé syndrome
• genetic lung disease
• pneumothorax
• pulmonary cysts