scholarly journals Birt–Hogg–Dubé syndrome in Chinese patients: a literature review of 120 families

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiaowen Hu ◽  
Guofeng Zhang ◽  
Xianmeng Chen ◽  
Kai-Feng Xu
Keyword(s):  
Spontaneous Pneumothorax ◽  
Delayed Diagnosis ◽  
Clinical Manifestations ◽  
Lower Lobe ◽  
Skin Lesions ◽  
Jiangsu Province ◽  
Chinese Patients ◽  
Renal Tumors ◽  
Pulmonary Cysts ◽  
Exon 11

Abstract Objective To clarify the epidemiological and clinical features of Birt–Hogg–Dubé syndrome (BHDS) in Chinese patients. Methods We identified reports on Chinese patients with BHDS by searching the China Academic Journals Database, Wanfang Chinese Database, and PubMed databases, either in Chinese or English languages published from January 1, 2008 to December 31, 2020. Studies without sufficient clinical data were excluded and cases under 18 years old were excluded. Results Twenty papers were included and comprised 120 families with 221 cases. Most families with BHDS were reported from institutions in Beijing (66.7%) and Jiangsu Province (15.8%); 80.8% of cases were reported within the past five years. The average duration from clinical presentation to diagnosis was 9.6 years. The average age was 47.0 ± 13.9 years (range, 18–84 years) and the ratio of male to female was 1:1.6. The most common manifestations of BHDS were multiple pulmonary cysts (92.4%), spontaneous pneumothorax (71.0%), skin lesions (18.1%) and renal tumors (3.6%). Pulmonary cysts were predominantly distributed in the lower lobe on chest CT imaging. Family history of spontaneous pneumothorax was identified in 84.7% of the families and average number of pneumothoraxes was 1.8 (range, 1–6). The FLCN gene mutation c.1285dupC/delC in exon 11 was the most frequent mutation observed (17.4% of patients). The recurrence rate of pneumothorax after conservative treatment (including tube thoracostomy) was 29/41 (71%) while the pneumothorax recurred after surgical treatment (pulmonary bullectomy or pleurodesis) in only 4/37 (11%). Conclusions Although BHDS has been increasingly reported in the recent years, only minority of families were reported from institutions outside of Beijing and Jiangsu Province. The dominant clinical manifestations were pulmonary cysts associated with recurrent pneumothorax, while skin lesions and renal tumors were less commonly reported. Delayed diagnosis along with suboptimal management appear to represent critical challenges for Chinese patients with BHDS.

Birt-Hogg-Dubé Syndrome in Chinese Patients: A Literature Review of 120 Families

2021 ◽  
Author(s):  
Guofeng Zhang ◽  
Xianmeng Chen ◽  
Kaifeng Xu ◽  
Xiaowen Hu
Keyword(s):  
Spontaneous Pneumothorax ◽  
Delayed Diagnosis ◽  
Clinical Manifestations ◽  
Lower Lobe ◽  
Skin Lesions ◽  
Jiangsu Province ◽  
Chinese Patients ◽  
Renal Tumors ◽  
Pulmonary Cysts ◽  
Exon 11

Abstract ObjectiveTo clarify the epidemiological and clinical features of Birt-Hogg-Dubé syndrome (BHDS) in Chinese patients. MethodsWe identified reports on Chinese patients with BHDS by searching the China Academic Journals Database, Wanfang Chinese Database, and PubMed databases, either in Chinese or English languages published from January 1, 2006 to December 31, 2020. Studies without sufficient clinical data were excluded and cases under 18 years old were excluded. ResultsTwenty papers were included and comprised 120 families with 221 cases. Most families with BHDS were reported from institutions in Beijing (66.7%) and Jiangsu Province (15.8%); 80.8% of cases were reported within the past five years. The average duration from clinical presentation to diagnosis was 9.6 years. The average age was 47.0±13.9 years (range, 18-84 years) and the ratio of male to female was 1:1.6. The most common manifestations of BHDS were multiple pulmonary cysts (92.4%), spontaneous pneumothorax (71.0%), skin lesions (18.1%) and renal tumors (3.6%). Pulmonary cysts were predominantly distributed in the lower lobe on chest CT imaging. Family history of spontaneous pneumothorax was identified in 84.7% of the families and average number of pneumothoraxes was 1.8 (range, 1-6). The FLCN gene mutation c.1285dupC/delC in exon 11 was the most frequent mutation observed (17.4% of patients). The recurrence rate of pneumothorax after conservative treatment (including tube thoracostomy) was 29/41 (71%) while the pneumothorax recurred after surgical treatment (pulmonary bullectomy or pleurodesis) in only 4/37 (11%).ConclusionsAlthough BHDS has been increasingly reported in the recent years, only minority of families were reported from institutions outside of Beijing and Jiangsu Province. The dominant clinical manifestations were pulmonary cysts associated with recurrent pneumothorax, while skin lesions and renal tumors were less commonly reported. Delayed diagnosis along with suboptimal management appear to represent critical challenges for Chinese patients with BHDS.

scholarly journals Genotypic characteristics of Chinese patients with BHD syndrome and functional analysis of FLCN variants

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Keqiang Liu ◽  
Wenshuai Xu ◽  
Xinlun Tian ◽  
Meng Xiao ◽  
Xinyue Zhao ◽  
...  
Keyword(s):  
Clinical Features ◽  
Spontaneous Pneumothorax ◽  
Mutation Screening ◽  
Skin Lesions ◽  
Mrna Splicing ◽  
Mutation Spectrum ◽  
Chinese Patients ◽  
Renal Tumors ◽  
Lung Cysts ◽  
Splicing Pattern

Abstract Background Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant disease featured by lung cysts, spontaneous pneumothorax, fibrofolliculomas and renal tumors. The causative gene for BHDS is the folliculin (FLCN) gene and more than 200 mutations have been reported in FLCN, mostly truncating mutations. The aim of this study is to better characterize the clinical features and mutation spectrum of Chinese BHDS patients and to systematically evaluate the effects of non-truncating mutations on mRNA splicing pattern. Methods We enrolled 47 patients from 39 unrelated families with symptoms highly suggestive of BHDS after informed consent and detailed clinical data were collected. Exon sequencing followed by multiplex ligation-dependent probe amplification testing were applied for mutation screening. The effects of non-truncating mutations, including 15 missense mutations and 6 in-frame deletions, on mRNA splicing were investigated by minigene assays. Results A total of 24 FLCN germline variants were found in 39 patients from 31 distinct families. Out of these patients, 100% (36/36) presented with lung cysts and 58.3% (21/36) had experienced spontaneous pneumothorax. Seventeen mutation carriers had skin lesions (47.2%, 17/36) and 9 (30%, 9/30) had kidney lesions including 8 with renal cysts and 1 with renal hamartoma. Among all detected variants 14 (58.3%, 14/24) were novel, including 11 variants classified to be pathogenic and 3 variants of uncertain significance. None of 21 non-truncating mutations changed the mRNA splicing pattern of minigenes. Conclusions We found different clinical features of Chinese BHDS patients compared with Caucasians, with more lung cysts and pneumothorax but fewer skin lesions and malignant renal cancer. Chinese patients with BHDS also have a different mutation spectrum from other races. Non-truncating mutations in FLCN did not disrupt mRNA splicing pattern, in turn supporting the hypothesis that these mutations impair folliculin function by disrupting the stability of the FLCN gene product.

scholarly journals A Young Man with Bilateral Spontaneous Pneumothorax

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Liese Lieve Willemien Verhaert
Keyword(s):  
Spontaneous Pneumothorax ◽  
Positive Family History ◽  
Clinical Manifestations ◽  
Sudden Onset ◽  
Renal Tumors ◽  
High Resolution Computed Tomography ◽  
Thoracic Pain ◽  
Pulmonary Cysts ◽  
Lower Lung ◽  
Wide Variability

Case.A 33-year-old male nonsmoker presented with sudden onset of dyspnoea and thoracic pain. Chest radiograph showed a left-sided pneumothorax. Few days later he developed a right-sided pneumothorax. He had a positive family history of pneumothorax. High-resolution computed tomography of the chest showed multiple pulmonary cysts predominantly located in the lower lung regions. We suspected Birt-Hogg-Dubé syndrome (BHD).Conclusion.Birt-Hogg-Dubé syndrome is a rare autosomal dominant inherited genodermatosis and characterised by clinical manifestations including hamartomas of the skin, renal tumors, and pulmonary cysts with spontaneous pneumothorax. BHD is probably underdiagnosed because of the wide variability in its clinical expression. It is important to recognize these patients because of the possibility of developing renal cancer.

scholarly journals Birt-Hogg-Dubé syndrome presenting with spontaneous pneumothorax and extensive pulmonary cysts in the absence of skin lesions or renal pathology

2019 ◽  
Vol 12 (9) ◽  
pp. e231039
Author(s):  
Kartik Kumar ◽  
Clare Ross
Keyword(s):  
Spontaneous Pneumothorax ◽  
Autosomal Dominant ◽  
Skin Lesions ◽  
Lung Cysts ◽  
Cystic Lung ◽  
Increased Risk ◽  
Renal Tumours ◽  
Pulmonary Cysts ◽  
Dominant Condition ◽  
Bhd Syndrome

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition which classically manifests with skin lesions such as fibrofolliculomas, pulmonary cysts that predispose to spontaneous pneumothorax and an increased risk of developing renal cell carcinoma. We describe the case of a patient who presented with a spontaneous pneumothorax on a background of multiple lung cysts, in the absence of cutaneous fibrofolliculomas and renal tumours. A germline mutation in the folliculin FLCN gene was subsequently identified, confirming BHD syndrome. Our case highlights the importance of considering a broad differential diagnosis for the cause of a spontaneous pneumothorax in the presence of unexplained cystic lung disease and emphasises the value of maintaining a high index of clinical suspicion for inherited causes of pneumothoraces.

Multiple Chromophobe and Clear Cell Renal Cancer in A Patient Affected by Birt-Hogg-Dubè Syndrome: A Case Report

2016 ◽  
Vol 84 (2) ◽  
pp. 116-120
Author(s):  
Roberto Castellucci ◽  
Michele Marchioni ◽  
Sergio Valenti ◽  
Giuseppe Sortino ◽  
Giulio Borgonovo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cancer ◽  
Renal Cell ◽  
Spontaneous Pneumothorax ◽  
Clear Cell ◽  
Renal Tumors ◽  
Kidney Tumors ◽  
Pulmonary Cysts

Objectives Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. The syndrome is linked to mutations in the FLCN gene, which is preferentially expressed in the skin, kidney, and lung. The aim of our paper is to describe a case of multiple bilateral renal cancer in a patient affected by BHDS. Case Presentation Patient subjected to enucleoresection seven kidney tumors discovered right after ultrasound performed for other reasons. Definitive histologic examination were as follows: multifocal type chromophobe renal cell carcinoma and clear cell. After 1 month, the patient was readmitted for spontaneous pneumothorax. After about a year, the patient was again subjected to resection of multiple renal tumors left. Histological examination proved that it was multifocal renal cell carcinoma, clear cell varieties. The genome analysis highlighted positive for mutation c. 1379_1380 of FLCN gene, BHDS gene. Currently, the patient is under close follow-up. After 1 year, the chest computed tomography (CT) confirmed the presence of minute air bubbles scattered on both sides. Instead, the abdominal CT was positive for a small round lesion 6 mm exophytic. Conclusions The BHDS is a rare syndrome whose management is extremely complex both in terms of oncological and functional. Kidney tumors associated with BHDS usually have a favorable clinical course. Present evidence suggests a close follow-up of the carriers of the genetic mutation patients whether or not they have expressed the lesions of disease given the high rate of recurrence of renal lesions.

scholarly journals A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Minghui Cai ◽  
Xinxin Zhang ◽  
Lizhen Fan ◽  
Shuwen Cheng ◽  
Abdukahar Kiram ◽  
...  
Keyword(s):  
Spontaneous Pneumothorax ◽  
Relevant Literature ◽  
Skin Lesions ◽  
Targeted Next Generation Sequencing ◽  
Advantages And Disadvantages ◽  
Intragenic Deletion ◽  
Pulmonary Cysts ◽  
Targeted Ngs ◽  
Atypical Manifestations ◽  
Intragenic Deletions

Birt–Hogg–Dubé syndrome (BHDS, MIM #135150), caused by germline mutations of FLCN gene, is a rare autosomal dominant inherited disorder characterized by skin fibrofolliculomas, renal cancer, pulmonary cysts and spontaneous pneumothorax. The syndrome is considered to be under-diagnosed due to variable and atypical manifestations. Herein we present a BHDS family. Targeted next generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) revealed a novel FLCN intragenic deletion spanning exons 10-14 in four members including the proband with pulmonary cysts and spontaneous pneumothorax, one member with suspicious skin lesions and a few pulmonary cysts, as well as two asymptomatic family members. In addition, a linkage analysis further demonstrated one member with pulmonary bullae to be a BHDS-ruled-out case, whose bullae presented more likely as an aspect of paraseptal emphysema. Furthermore, the targeted NGS and MLPA data including our previous and present findings were reviewed and analyzed to compare the advantages and disadvantages of the two methods, and a brief review of the relevant literature is included. Considering the capability of the targeted NGS method to detect large intragenic deletions as well as determining deletion junctions, and the occasional false positives of MLPA, we highly recommend targeted NGS to be used for clinical molecular diagnosis in suspected BHDS patients.

scholarly journals Congenital syphilis in Argentina: experience in a pediatric hospital

2020 ◽  
Author(s):  
Luciana Noemí Garcia ◽  
Alejandra Destito Solján ◽  
Nicolas Falk ◽  
Nicolás Leonel Gonzalez ◽  
Griselda Ballering ◽  
...  
Keyword(s):  
Medical Records ◽  
Congenital Syphilis ◽  
Delayed Diagnosis ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Penicillin G ◽  
High Morbidity ◽  
Laboratory Findings ◽  
Therapeutic Decisions

AbstractAlthough congenital syphilis (CS) is preventable, it is still an important health problem worldwide. Recently, an increase in the number of primary and congenital syphilis cases has been observed. Fetal infection can be particularly aggressive, but newborns can be asymptomatic at birth and run the risk of developing systemic compromise with a poor prognosis.We conducted a study (1987-2019) analyzing the medical records of CS diagnosis cases assisted at the Buenos Aires Children’ Hospital. Sixty-one patients were included. Information about demographics, clinical and laboratory findings, T. pallidum serology and treatment was collected. Median age at diagnosis was 2 months (IQ 1-6 months). The distribution of cases showed a bimodal curve, with a peak in 1993 and in 2017. The main clinical findings were: bone alterations in 36/61 (59%); hepatosplenomegaly in 33/61 (54.1%); anemia in 32/51 (62.8%); skin lesions 26/61 (42.6%) and renal compromise in 15/45 (33.3%). Cerebrospinal fluid was studied in 50/61 (81.9%); 5 (10%) were abnormal (reactive VDRL and/or cell alteration count). Only 23 (60.5%) patients had nontreponemal titers fourfold higher than their mothers did. Intravenous penicillin G for an average of 10-14 days was prescribed in 60/61 subjects and one patient received ceftriaxone. Remarkably, only 28 (46%) mothers were tested for syphilis during pregnancy.During follow-up, a decrease in RPR titers was observed reaching seroconversion in 31/34 (91%) subjects at a median of 19.2 months after treatment. Treponemal titers (TPHA) remained reactive.Our results highlighted that an increase in the number of cases of CS is occurring in our population with high morbidity related to delayed diagnosis. A good therapeutic response was observed.CS requires a greater effort from obstetricians to adequately screen for the disease during pregnancy and pediatricians should be alert in order to detect cases earlier, to provide an adequate diagnosis and treatment of CS.Author SummaryCS is caused by mother-to child transmission. Although screening of pregnant women and treatments are available, new cases are increasing worldwide. We reviewed the medical records of CS-patients assisted in our hospital over the past 30 years. Our results showed that there was an increase in the number of CS cases. At birth, most children were asymptomatic and later developed CS clinical manifestations. Penicillin treatment, and in one case ceftriaxone, was prescribed with a good clinical response. Nevertheless, one infant died, four had persistent kidney disorders and one showed bone sequelae damage. Spinal lumbar puncture did not modify therapeutic decisions. In the follow-up, a decrease in nontreponemal antibodies was observed as a marker of treatment response. We concluded that the detection and treatment of CS remains a great challenge for clinical practice in our region.It is crucial that pediatricians and obstetricians give greater attention and make a greater effort to detect this neglected disease in an attempt to reverse its upwards trend.

scholarly journals Characterization of CT scan in Birt-Hogg-Dubé syndrome compared with non-BHD diffuse cysts lung diseases in Chinese Patients

2019 ◽  
Author(s):  
WenShuai Xu ◽  
Zhiyan Xu ◽  
Yaping Liu ◽  
Yongzhong Zhan ◽  
Xin Sui ◽  
...  
Keyword(s):  
Lung Diseases ◽  
Lower Lobe ◽  
Ct Images ◽  
Chinese Patients ◽  
Axial Distribution ◽  
Lung Cysts ◽  
Cystic Lung ◽  
Pulmonary Cysts ◽  
Lower Lung ◽  
Bhd Syndrome

Abstract Background and objective: 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). Methods: The study was a retrospective review of the CT images of 18 patients with BHD syndrome, 18 patients with LAM, and 16 patients with NBNL (non-BHD and non-LAM) DCLD patients. On the basis of the data collected, the CT images were reviewed again to evaluate the characteristics (size, number, distribution, morphology) of pulmonary cysts. Results: Lower lung–predominant cysts were prone to be found in patients with BHD syndrome than in patients with LAM, but there is no difference between BHD and NBNL DCLD group. In the axial distribution, 9 of 18 patients in BHD-group had cysts predominance near the mediastinum, relatively, all the patients in the non-BHD group have diffuse cysts. The appearance of fusiform cysts was easier observed in patients of BHD group. Most patients in BHD-group had less than 50 lung cysts, while all patients in non-BHD group had more than 50 lung cysts. The maximum cyst located in the lower lobe in 16 of 18 patients in BHD-group, while 6 of 18 patients in LAM group and 8 patients in NBNL DCLD group had the maximum cyst in the lower lobe. Conclusion: The pulmonary cysts in patients with BHD tend to be fusiform, less numerous, and have a predominance in the lower lobe and near the mediastinum. These radiologic pulmonary features could assist physicians differentiating BHD from other DCLDs.

scholarly journals Characterization of CT scans of patients with Birt-Hogg-Dubé syndrome compared with those of Chinese patients with non-BHD diffuse cyst lung diseases

2020 ◽  
Author(s):  
WenShuai Xu ◽  
Zhiyan Xu ◽  
Yaping Liu ◽  
Yongzhong Zhan ◽  
Xin Sui ◽  
...  
Keyword(s):  
Lung Diseases ◽  
Lower Lobe ◽  
Ct Images ◽  
Chinese Patients ◽  
Axial Distribution ◽  
Lung Cysts ◽  
Cystic Lung ◽  
Pulmonary Cysts ◽  
Lower Lung ◽  
Bhd Syndrome

Abstract Background and objective: 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).Methods: 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.Results: 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.Conclusion: 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.

scholarly journals Prevalence of Birt-Hogg-Dubé Syndrome Determined Through Epidemiological Data on Spontaneous Pneumothorax and Bayes Theorem

2021 ◽  
Vol 8 ◽  
Author(s):  
Marie-Eve Muller ◽  
Cécile Daccord ◽  
Patrick Taffé ◽  
Romain Lazor
Keyword(s):  
General Population ◽  
Incidence Rate ◽  
Spontaneous Pneumothorax ◽  
Meta Analysis ◽  
Epidemiological Data ◽  
Bayes Theorem ◽  
Renal Tumors ◽  
Published Data ◽  
Pulmonary Cysts ◽  
Before And After

Background: Birt-Hogg-Dubé syndrome (BHD) is a rare inherited disorder characterized by cutaneous fibrofolliculomas, multiple pulmonary cysts, recurrent spontaneous pneumothorax (SP), and renal tumors. More than 40 years after its description, the prevalence of BHD in the general population remains unknown. This study aimed at determining the prevalence of BHD by applying the Bayes theorem of conditional probability to epidemiological data on SP.Methods: We performed a meta-analysis of published data on: (1) the probability of having BHD among patients with apparent primary SP (4 studies), (2) the incidence rate of primary SP in the general population (9 studies), and (3) the probability of experiencing a SP in BHD (16 studies). Results were corrected for SP relapses, stratified by gender and year of study publication (before and after 2000), and computed with the Bayes equation.Results: The probability of having BHD among patients with apparent primary SP was 0.09 (95% confidence interval: 0.07, 0.11) or 9%. It was 0.20 (0.14, 0.27) in women and 0.05 (0.04, 0.07) in men. The incidence rate of primary SP in the general population was 8.69 (6.58, 11.46) per 100,000 person-years (p-y). It was 3.44 (2.36, 4.99) per 100,000 p-y in women and 13.96 (10.72, 18.18) per 100,000 p-y in men, and was about 2 times higher in studies published after 2000 than in those published before 2000. The probability of experiencing at least one SP among patients with BHD was 0.43 (0.31, 0.54) or 43%, without gender difference. By combining these data in the Bayes equation, we found a prevalence of BHD in the general population of 1.86 (1.16, 3.00) per million, with values of 1.86 (1.02, 3.39) per million in men, and 1.88 (0.97, 3.63) per million in women.Conclusion: The prevalence of BHD in the general population is about 2 cases per million, without difference between genders.

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