BACKGROUND Birt-Hogg-Dubé(BHD)syndrome is a rare autosomal dominant disease caused by germline mutations in the folliculin(FLCN)protein gene,which usually manifests as cutaneous fibrofolliculoma,pulmonary cysts,r...BACKGROUND Birt-Hogg-Dubé(BHD)syndrome is a rare autosomal dominant disease caused by germline mutations in the folliculin(FLCN)protein gene,which usually manifests as cutaneous fibrofolliculoma,pulmonary cysts,renal cell carcinoma,and spontaneous pneumothorax.CASE SUMMARY A 26-year-old woman with no history of smoking was admitted to the Respiratory Department of our hospital due to intermittent wheezing that lasted for 8 mo.She had experienced recurrent spontaneous pneumothorax more than four times during the past 8 mo.After admission,the patient again suffered from left pneumothorax without a clear reason.Lung computed tomography(CT)showed multiple low-density cystic changes in both lungs.Physical examination on admission revealed multiple white dome-shaped papules in the neck,the nape,and behind the ear.In addition,the patient had a family history of spontaneous pneumothorax.Her mother had suffered from pneumothorax four times(at age 36,37,42,and 50 years).Her second maternal aunt had suffered from a right pneumothorax at the age of 40.The multidisciplinary diagnosis of BHD,which included the Respiratory Department,Radiology Department,Pathology Department,and Dermatological Department,was BHD and was later confirmed by family genetic testing.The same variation(FLCN gene)was found in the patient’s mother and aunt.CONCLUSION This case highlights the importance of multidisciplinary diagnosis and a treatment platform for the diagnosis of BHD.展开更多
Background: Birt- Hogg- Dubé syndrome (BHD) is a rare autosomal dominant genodermatosis characterized by skin tumours, including multiple fibrofolliculomas, trichodiscomas and acrochordons. BHD patients also may ...Background: Birt- Hogg- Dubé syndrome (BHD) is a rare autosomal dominant genodermatosis characterized by skin tumours, including multiple fibrofolliculomas, trichodiscomas and acrochordons. BHD patients also may suffer from associated renal and colonic carcinomas. The defective gene in BHD has been recently identified and is suspected of being a tumour suppressor gene. Several mutations of the BHD gene have been reported only in Caucasian patients. Objectives: This study reports the first Asian family that has been demonstrated to carry a BHD mutation. Patients/methods: The proband was a 26- year- old Japanese man with multiple asymptomatic, soft skin- coloured papules on his face, neck and trunk, which were clinically thought to be acrochordon. His father was also affected. Histopathologically, the papules revealed a fibrofolliculoma that had a circumscribed proliferation of fibroblasts and collagen fibres surrounding an abnormal hair follicle. Results: Mutational analysis of the BHD gene of the proband and the father detected 1733insC, a cytosine insertion mutation in an eight- cytosine tract (nucleotides 1733- 1740) in exon 11. Analysis of fibrofolliculoma in the proband showed heterozygous 1733insC mutation, suggesting the absence of loss of heterozygosity. Interestingly, previous mutational analysis in Caucasian patients revealed that both1733insC and 1733delC mutations were hot spots. Conclusions: This study is the first to find the same hot- spot 1733insC mutation in Asian kindred. The mutations in this polycytosine tract may have a wide, global distribution despite their arising from a different ethnic background.展开更多
Birt-Hogg-Dubésyndrome (BHDS) is an uncommon autosomal dominant genodermatosis characterized by a triad of skin tumors-fibrofolliculomas, trichodiscomas, and acrochordons-together with an increased risk of renal ...Birt-Hogg-Dubésyndrome (BHDS) is an uncommon autosomal dominant genodermatosis characterized by a triad of skin tumors-fibrofolliculomas, trichodiscomas, and acrochordons-together with an increased risk of renal tumors and spontaneous pneumothoraces. This report describes multiple facial angiofi-bromas as the predominant initial manifestation of BHDS. The patient had a total of 41 facial papules removed via shave excision, initially for diagnostic and then for therapeutic purposes; histologic evaluation revealed diagnostic features of angiofi-broma in 39 lesions and fibrofolliculoma in only 2. BHDS should be considered, along with tuberous sclerosis and multiple endocrine neoplasia type 1, in the differential diagnosis of multiple facial angiofibromas, particularly when onset is in adulthood.展开更多
Birt-Hogg-Dubésyndrome is an autosomal dominant condition characterized by a triad of fibrofolliculomas, trichodiscomas, and acrochordons. Since the first description in 1977, many conditions have been described ...Birt-Hogg-Dubésyndrome is an autosomal dominant condition characterized by a triad of fibrofolliculomas, trichodiscomas, and acrochordons. Since the first description in 1977, many conditions have been described in association with its clinical triad. Recent epidemiological studies have shown a significant association between the occurrence of lesions in the fibrofolliculoma/ trichodiscoma category with renal neoplasms and pneumothoracies. The BHD protein folliculin had recently been identified. The histological findings of the clinical lesions are distinctive. We report a patient with a history of melanoma who presented for routine surveillance. Facial lesions in the fibrofolliculoma/trichodiscoma category were identified. Diagnostic work-up revealed concomitant multinodular goiter, pulmonary cyst, and renal mass. The patient later developed pneumothorax. Clinical manifestations, histological findings, associations, management, and a review of the Birt-Hogg-DubéSyndrome are discussed.展开更多
Rationale and Objectives: Cystic lung disease may be accurately diagnosed by imaging interpretation of specialist radiologists, without other information. We hypothesized that with minimal training non-specialists cou...Rationale and Objectives: Cystic lung disease may be accurately diagnosed by imaging interpretation of specialist radiologists, without other information. We hypothesized that with minimal training non-specialists could perform similarly to specialist physicians in the diagnosis of cystic lung disease. Methods: 72 cystic lung disease cases and 25 cystic lung disease mimics were obtained from three sources: 1) a prospective acquired diffuse lung disease registry, 2) a retrospective search of medical records and 3) teaching files. Cases were anonymized, randomized and interpreted by 7 diffuse lung disease specialists and 15 non-specialist radiologists and pulmonologists. Clinical information other than age and sex was not provided. Prior to interpretation, non-specialists viewed a short PDF training document explaining cystic lung disease interpretation. Results: Correct first choice diagnosis of 85%-88% may be achieved by high-performing specialist readers and 71%-80% by non-specialists and lower-performing specialists, with mean accuracies in the diagnosis of LAM (91%, p Conclusion: With specific but limited training, non-specialist physicians can diagnose cystic lung diseases from CT appearance alone with similar accuracy to specialists, correctly identifying approximately 75% of cases.展开更多
A 69-year-old man with multiple skin lesions on his face, neck and upper torso, which first appeared in the 3rd decade of his life, was admitted to our hospital. He had cystic changes in his lungs noted on chest compu...A 69-year-old man with multiple skin lesions on his face, neck and upper torso, which first appeared in the 3rd decade of his life, was admitted to our hospital. He had cystic changes in his lungs noted on chest computed to- mography （CT） scanning, as well as a left kidney mass. This patient exhibited a rare complex of renal, cutaneous and pulmonary manifestations, eponymously named Birt-Hogg-Dube syndrome, with characteristic skin features （fibrofolliculomas, trichodiscomas and acrochordons）. This syndrome is due to an autosomal dominant germ-line mutation of thefolliculin （FLCN） gene located at chromosome 17p11.2. Diagnosis and differentiation from other disease complexes including the skin, kidneys and lungs are important in prognostication and management of po- tentially life-threatening complications such as renal cell carcinoma and pneumothoraces.展开更多
Birt–Hogg–Dubé(BHD) syndrome, a hereditary renal cancer syndrome caused by mutations in the folliculin(FLCN) gene, is characterized by the presence of ibrofolliculomas, pulmonary cysts, spontaneous pneumothorax...Birt–Hogg–Dubé(BHD) syndrome, a hereditary renal cancer syndrome caused by mutations in the folliculin(FLCN) gene, is characterized by the presence of ibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal cell carcinoma(RCC). Few BHD syndrome cases have been reported in Asian countries, and cutaneous presentations are relatively rare in Asian patients. Asian BHD patients may be misdiagnosed due to their atypical manifestations. Here, we report two Chinese BHD patients with novel FLCN mutations(c.946-947 del AG in exon 9 and c.770-772 del CCT in exon 7). Both of them had RCC and spontaneous pneumothorax without ibrofolliculomas. In patients with RCC and pulmonary cysts but without cutaneous lesions, screening for mutations in the FLCN gene should be performed, especially for those with a family history of RCC or pulmonary cysts(pneumothorax).展开更多
文摘BACKGROUND Birt-Hogg-Dubé(BHD)syndrome is a rare autosomal dominant disease caused by germline mutations in the folliculin(FLCN)protein gene,which usually manifests as cutaneous fibrofolliculoma,pulmonary cysts,renal cell carcinoma,and spontaneous pneumothorax.CASE SUMMARY A 26-year-old woman with no history of smoking was admitted to the Respiratory Department of our hospital due to intermittent wheezing that lasted for 8 mo.She had experienced recurrent spontaneous pneumothorax more than four times during the past 8 mo.After admission,the patient again suffered from left pneumothorax without a clear reason.Lung computed tomography(CT)showed multiple low-density cystic changes in both lungs.Physical examination on admission revealed multiple white dome-shaped papules in the neck,the nape,and behind the ear.In addition,the patient had a family history of spontaneous pneumothorax.Her mother had suffered from pneumothorax four times(at age 36,37,42,and 50 years).Her second maternal aunt had suffered from a right pneumothorax at the age of 40.The multidisciplinary diagnosis of BHD,which included the Respiratory Department,Radiology Department,Pathology Department,and Dermatological Department,was BHD and was later confirmed by family genetic testing.The same variation(FLCN gene)was found in the patient’s mother and aunt.CONCLUSION This case highlights the importance of multidisciplinary diagnosis and a treatment platform for the diagnosis of BHD.
文摘Background: Birt- Hogg- Dubé syndrome (BHD) is a rare autosomal dominant genodermatosis characterized by skin tumours, including multiple fibrofolliculomas, trichodiscomas and acrochordons. BHD patients also may suffer from associated renal and colonic carcinomas. The defective gene in BHD has been recently identified and is suspected of being a tumour suppressor gene. Several mutations of the BHD gene have been reported only in Caucasian patients. Objectives: This study reports the first Asian family that has been demonstrated to carry a BHD mutation. Patients/methods: The proband was a 26- year- old Japanese man with multiple asymptomatic, soft skin- coloured papules on his face, neck and trunk, which were clinically thought to be acrochordon. His father was also affected. Histopathologically, the papules revealed a fibrofolliculoma that had a circumscribed proliferation of fibroblasts and collagen fibres surrounding an abnormal hair follicle. Results: Mutational analysis of the BHD gene of the proband and the father detected 1733insC, a cytosine insertion mutation in an eight- cytosine tract (nucleotides 1733- 1740) in exon 11. Analysis of fibrofolliculoma in the proband showed heterozygous 1733insC mutation, suggesting the absence of loss of heterozygosity. Interestingly, previous mutational analysis in Caucasian patients revealed that both1733insC and 1733delC mutations were hot spots. Conclusions: This study is the first to find the same hot- spot 1733insC mutation in Asian kindred. The mutations in this polycytosine tract may have a wide, global distribution despite their arising from a different ethnic background.
文摘Birt-Hogg-Dubésyndrome (BHDS) is an uncommon autosomal dominant genodermatosis characterized by a triad of skin tumors-fibrofolliculomas, trichodiscomas, and acrochordons-together with an increased risk of renal tumors and spontaneous pneumothoraces. This report describes multiple facial angiofi-bromas as the predominant initial manifestation of BHDS. The patient had a total of 41 facial papules removed via shave excision, initially for diagnostic and then for therapeutic purposes; histologic evaluation revealed diagnostic features of angiofi-broma in 39 lesions and fibrofolliculoma in only 2. BHDS should be considered, along with tuberous sclerosis and multiple endocrine neoplasia type 1, in the differential diagnosis of multiple facial angiofibromas, particularly when onset is in adulthood.
文摘Birt-Hogg-Dubésyndrome is an autosomal dominant condition characterized by a triad of fibrofolliculomas, trichodiscomas, and acrochordons. Since the first description in 1977, many conditions have been described in association with its clinical triad. Recent epidemiological studies have shown a significant association between the occurrence of lesions in the fibrofolliculoma/ trichodiscoma category with renal neoplasms and pneumothoracies. The BHD protein folliculin had recently been identified. The histological findings of the clinical lesions are distinctive. We report a patient with a history of melanoma who presented for routine surveillance. Facial lesions in the fibrofolliculoma/trichodiscoma category were identified. Diagnostic work-up revealed concomitant multinodular goiter, pulmonary cyst, and renal mass. The patient later developed pneumothorax. Clinical manifestations, histological findings, associations, management, and a review of the Birt-Hogg-DubéSyndrome are discussed.
文摘Rationale and Objectives: Cystic lung disease may be accurately diagnosed by imaging interpretation of specialist radiologists, without other information. We hypothesized that with minimal training non-specialists could perform similarly to specialist physicians in the diagnosis of cystic lung disease. Methods: 72 cystic lung disease cases and 25 cystic lung disease mimics were obtained from three sources: 1) a prospective acquired diffuse lung disease registry, 2) a retrospective search of medical records and 3) teaching files. Cases were anonymized, randomized and interpreted by 7 diffuse lung disease specialists and 15 non-specialist radiologists and pulmonologists. Clinical information other than age and sex was not provided. Prior to interpretation, non-specialists viewed a short PDF training document explaining cystic lung disease interpretation. Results: Correct first choice diagnosis of 85%-88% may be achieved by high-performing specialist readers and 71%-80% by non-specialists and lower-performing specialists, with mean accuracies in the diagnosis of LAM (91%, p Conclusion: With specific but limited training, non-specialist physicians can diagnose cystic lung diseases from CT appearance alone with similar accuracy to specialists, correctly identifying approximately 75% of cases.
文摘A 69-year-old man with multiple skin lesions on his face, neck and upper torso, which first appeared in the 3rd decade of his life, was admitted to our hospital. He had cystic changes in his lungs noted on chest computed to- mography （CT） scanning, as well as a left kidney mass. This patient exhibited a rare complex of renal, cutaneous and pulmonary manifestations, eponymously named Birt-Hogg-Dube syndrome, with characteristic skin features （fibrofolliculomas, trichodiscomas and acrochordons）. This syndrome is due to an autosomal dominant germ-line mutation of thefolliculin （FLCN） gene located at chromosome 17p11.2. Diagnosis and differentiation from other disease complexes including the skin, kidneys and lungs are important in prognostication and management of po- tentially life-threatening complications such as renal cell carcinoma and pneumothoraces.
基金supported by the National Natural Science Foundation of China(Grant Number:81172418)the Beijing Municipal Natural Science Foundation(Grant Number:7142160)
文摘Birt–Hogg–Dubé(BHD) syndrome, a hereditary renal cancer syndrome caused by mutations in the folliculin(FLCN) gene, is characterized by the presence of ibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal cell carcinoma(RCC). Few BHD syndrome cases have been reported in Asian countries, and cutaneous presentations are relatively rare in Asian patients. Asian BHD patients may be misdiagnosed due to their atypical manifestations. Here, we report two Chinese BHD patients with novel FLCN mutations(c.946-947 del AG in exon 9 and c.770-772 del CCT in exon 7). Both of them had RCC and spontaneous pneumothorax without ibrofolliculomas. In patients with RCC and pulmonary cysts but without cutaneous lesions, screening for mutations in the FLCN gene should be performed, especially for those with a family history of RCC or pulmonary cysts(pneumothorax).
