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Background: Birt-Hogg-Dubé (BHD) syndrome is a genetic condition caused by pathogenic variants in the FLCN gene resulting in benign skin lesions, spontaneous pneumothorax, and increased risk for a variety of renal tumors. Skin manifestations of BHD include trichodiscoma (TD) and fibrofolliculoma (FF), which may represent the same pathologic entity. These lesions can identify BHD patients, who upon positive genetic testing can be considered for life-long surveillance for renal neoplasms. Objective: To characterize patients diagnosed with TD and FF including rates and outcomes of genetics referral. Methods: Retrospective chart reviews of patients with confirmed or possible diagnosis of TD or FF at the University of Michigan from September 2002 through October 2020 to assess pathologic findings, personal and family history of BHD manifestations, referral for genetic evaluation, and genetic testing results. Results: 64 patients had a pathologic diagnosis of TD or FF, 16 of whom (25%) were referred to cancer genetics. Fourteen patients completed genetic evaluation, 9 of whom were diagnosed with BHD (64%), with 6 unique pathogenic variants in FLCN. Conclusion: Providers should consider referral for genetic evaluation for patients with biopsy-proven TD or FF, as early diagnosis of BHD provides the opportunity for early detection and treatment of other BHD-associated conditions. Capsule Summary: • Birt-Hogg-Dube syndrome includes renal cancer, pneumothorax, and trichodiscomas and fibrofolliculomas and is caused by pathogenic variants in FLCN. • Patients with trichodiscoma or fibrofolliculoma should be considered for referral to cancer genetics to allow identification of pathogenic FLCN variants and thus family cascade testing and surveillance for renal tumors. [ABSTRACT FROM AUTHOR]

Birt-Hogg-Dubé syndrome is a rare autosomal dominant hereditary disorder caused by a genetic mutation in the folliculin (FLCN) gene, characterized by benign fibrofolliculomas, increased risk of kidney tumors, lung cysts, and spontaneous pneumothorax. Genetic counseling for a mutation in the FLCN gene is recommended if specific criteria are met. Family members are eligible for genetic testing starting at age 20. For these patients, prevention of pneumothorax is crucial by avoiding deep-sea diving and smoking. Imaging of the kidneys is recommended due to the increased risk of renal cell carcinoma. An MRI scan should be performed at initial presentation, followed by annual monitoring through ultrasound. If kidney surgery is recommended, kidney-sparing surgery is preferred over radical nephrectomy due to the high risk of (contralateral) recurrence. [ABSTRACT FROM AUTHOR]

The Birt-Hogg-Dubé Syndrome (BHDs) can cause benign skin lesions like fibrofolliculomas as well as additional systemic symptoms like pulmonary cysts, kidney tumors, and recurrent pneumothoraces. We report the successful treatment of fibrofolliculomas in a patient with BHDs using a combination of fractionated ablative CO2 laser and a Flash Lamp Pulsed Dye Laser (FPDL). This combined method improves the CO2 healing process's functional and cosmetic results; while the first wavelength (ablative) has a greater capacity for excision and tissue regeneration, the second wavelength (non-ablative) provides more control over the tissue healing process. The lesions were successfully ablated up to the papillary dermis without leading to an enhancement in the overall textural appearance. Therefore, deeper laser ablations may be able to stop dermal residual lesion relapses. In conclusion, fractionated CO2 laser and FPDL can be used safely and effectively to reduce the appearance of facial hamartomas related to BHDs.

So far, confusion exists regarding the question of whether hereditary perifollicular fibromas and fibrofolliculomas can be distinguished from each other. Here, histopathological arguments are presented to clarify this terminological problem. In 1977, Birt et al. described a large kindred affected with hereditary multiple "fibrofolliculomas," which they thought were "a hitherto unrecognized pilar hamartoma," but they never claimed the fibrofolliculomas were part of a syndrome. A careful microscopic comparison shows, however, that the tumors are clinically and histopathologically identical to perifollicular fibromas, as first described by Burnier and Rejšek in 1925. Their familial occurrence was discovered in 1971 by Civatte and Le Tréguilly. Before 1977, the term "perifollicular fibroma" was used for these skin tumors. By contrast, Hornstein and Knickenberg described in 1975 perifollicular fibromas as a cutaneous marker of a syndrome characterized by a predisposition to colon cancer and pneumothorax. Later, two French groups erroneously proposed the term "Birt–Hogg–Dubé syndrome" to describe the co‐occurrence of fibrofolliculomas, trichodiscomas, and acrochordons, which was contrary to what Birt et al. had in mind. Hence, today, we should discriminate between the hereditary nonsyndromic perifollicular fibromas, as documented by Civatte and Le Tréguilly and later by Birt et al., and the syndromic perifollicular fibromas, as delineated by Hornstein and Knickenberg. [ABSTRACT FROM AUTHOR]

Birt-Hogg-Dubé syndrome is a rare autosomal dominant disorder characterized by fibrofolliculomas, renal tumors, and lung cysts of varying sizes that exhibit a lentiform appearance. The cysts are typically small (less than 1 cm), thin-walled, and irregularly shaped, with a higher prevalence in the basal and mediastinal regions of the lungs. Approximately 30% of patients experience one or multiple pneumothoraces before reaching 40 years of age. Unlike in other cystic lung diseases, lung cysts in this condition do not show progression. Malignant renal tumors manifest in 12-35% of individuals before the age of 50, with surgical intervention being the preferred treatment option. As mortality frequently results from these renal tumors, expert consensus often advocated for screening starting at 21 years of age. Herein, we present a 68-year old male patient who presented with shortness of breath and cough. He had a history of pneumothorax 30 years ago. Computed tomography of the thorax revealed lentiform (lens-shaped) cysts of various sizes in the basal regions of the lungs. Since multiple fibrofolliculomas on the face and neck, Birt-Hogg-Dube sydrome was considered, and genetic screening was performed. A mutation in the Folliculin (FLCN) gene was identified. Abdominal Magnetic Resonance Imaging (MRI) was performed to assess for kidney tumors, but no pathology was identified. Although this patient does not have a renal tumor, we want to emphasize the need for MRI screening for renal tumors in patients with Birt-Hogg-Dube syndrome. Additionally, due to autosomal dominant inheritance, genetic screening is recommended for relatives. [ABSTRACT FROM AUTHOR]

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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.

Copyright of Dermatology Review / Przeglad Dermatologiczny is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: Fibrous cephalic plaques (FCPs) in individuals with tuberous sclerosis complex (TSC) may be excised for cosmetic reasons or biopsied to confirm lesion identification and TSC diagnosis. The aim of this study was to determine the range of histopathological features of FCPs. Methods and results: A retrospective analysis was conducted on 119 adults with TSC. Twenty‐one lesions from 16 individuals were evaluated by a dermatopathologist. Additionally, we assessed whether lesion colour or histology varied by anatomical location. Seventy‐six lesions were observed in 36 of 119 individuals. Erythematous lesions were more commonly found on the forehead, face or neck than on the scalp (odds ratio = 12.6, P = 0.0001). Thickened and disorganised collagen fibre bundles were present in 95% (20/21) of lesions. Perifollicular fibrosis was observed in 95% (20/21) of lesions, enhanced vascularity was observed in 52% (11/21) of lesions, and features of fibrofolliculoma were observed in 43% (9/21) of lesions. Other abnormalities included features similar to trichofolliculoma, follicular‐derived, infundibular‐type cysts, and abnormally arranged primitive hair follicles. Conclusions: FCPs in TSC show thickened bundles of collagen, and hamartomatous changes involving hair follicles. Recognition of these histopathological features may raise the possibility of unsuspected TSC or confirm FCP identification. [ABSTRACT FROM AUTHOR]

Birt-Hogg-Dube Syndrome (BHDS) is a rare autosomal dominant disorder characterized by fibrofolliculomas, renal tumors, pulmonary cysts and spontaneous pneumothoraces. BHDS is described by Birt et al. in 1977. The other common skin findings are trichodiscoma, perifollicular fibroma and acrochordon. Skin lesions are often located on the nose,forehead,cheek,neck and to a lesser extent on the trunk. The risk of developing renal tumors and pneumothorax increases for patients with BHDS during their lifetime and should be followed in this respect. The diagnosis is made by evaluating clinical findings, histopathological findings, and imaging methods. Ablative laser (erbium- YAG or carbon dioxide), electrocauterization and/or excision is recommended for the treatment of skin lesions. We present a case of BHDS. [ABSTRACT FROM AUTHOR]

Background/Aims Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disorder that is characterized by skin fibrofolliculomas, pulmonary cysts, and renal tumors. The objective of this study was to describe the features of Korean patients with BHD syndrome. Methods Clinical data were retrospectively reviewed in 12 patients (10 confirmed by direct sequencing of the folliculin (FLCN) gene and two confirmed by clinical diagnosis) diagnosed from 2004 to 2016 at Asan Medical Center, Seoul, South Korea. Criteria proposed by the European BHD consortium were used for diagnosis. Results The median follow-up was 52 months. The mean age was 41.3 years and 66.7% were female. Eight patients (66.7%) had a history of pneumothorax, which was recurrent in 75%. Skin lesions were detected in 25.0% and renal cancer in 25.0%. Among mutations of the FLCN gene, the duplication of cytosine in the C8 tract of exon 11 (c.1285dupC) was the most common (40%); however, a novel heterozygous sequence variant of c.31T>C (p.C11R) in exon 4 was detected in one patient. All patients had multiple and bilateral pulmonary cysts, distributed in predominantly lower, peripheral and subpleural regions of the lungs. Most patients showed preserved lung function that remained unchanged during follow-up, and two (16.7%) developed cancers (renal cancer in one and breast cancer in one). Conclusions Our data suggest that Korean patients with BHD syndrome may have a higher risk of pneumothorax, less frequent skin lesions, and a novel FLCN mutation compared to previous reports. Multiple bilateral and basal-predominant cysts were the most common radiologic features.

Copyright of Dermatology Review / Przeglad Dermatologiczny is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Multiple familial diseases in a single patient often present with overlapping symptomatology that confers difficulty in delineating a clinical diagnosis. Pedigree analysis has been a long-standing practice in the field of medical genetics to discover familial diseases. In recent years, whole exome sequencing (WES) has proven to be a useful tool for aiding physicians in diagnosing and understanding disease etiology. This report shows that pedigree analysis and WES are co-dependent processes in establishing diagnoses in a family with 4 different genetic disorders: Birt-Hogg-Dubé Syndrome, RRM2B-related mitochondrial disease, CDC73-related primary hyperparathyroidism, and familial prostate cancer. [ABSTRACT FROM AUTHOR]

Birt-Hogg-Dube syndrome is characterized by cutaneous findings, including fibrofolliculomas, angiofibromas, fibroepithelial polyps, and trichodiscomas. It is an inherited autosomal dominant disorder. This syndrome also includes extra-cutaneous findings, such as pulmonary cysts, spontaneous pneumothorax, and renal cancer. Because of the systemic involvement, early diagnosis and treatment are important. Here, we report the case of a 53-year-old man diagnosed as having Birt-Hogg-Dube syndrome.

Background Birt-Hogg-Dubé syndrome (BHDS) (OMIM #135150) is an autosomal dominant disease, characterized by fibrofolliculomas (FFs) of the skin, pulmonary cysts with/without pneumothorax, and renal tumors. The prevalence of skin manifestations reported for Japanese BHDS patients is lower (<30%) compared with that of Western countries (75 ∼ 90%), which appear to be underestimated. Objective To precisely examine the prevalence of skin lesions with dermoscopy and histopathology with reference to genetic analyses. Methods We studied 31 patients (47.0 ± 13.2 years old, range 15–71) consisting of 26 unrelated families consecutively from May 2013 to June 2015 specifically for skin-colored papules on their faces and cervicothoracic regions. Patients initially suspected of BHDS from multiple pulmonary cysts that resulted in pneumothorax (30/31; 96.8%) received dermoscopic examinations and skin biopsies if applicable. The diagnosis of BHDS was established by folliculin ( FLCN ) genetic testing, and the results were compared to the histopathological findings of FFs or trichodiscomas (TDs). Results FLCN germline mutation was demonstrated in 25/26 (96.2%) unrelated families tested and 28/29 patients (96.6%) tested. Skin lesions were recognized in 26/31 patients (83.9%); skin biopsies were performed in 23 patients of whom FFs and/or TDs were histologically demonstrated in 17 (73.9%). Although our study population included patients whose skin manifestations were evaluated prior to or after FLCN genetic testing, skin lesions were clearly prevalent and recognizable irrespective of whether genetic testing was or wasn’t done. When examined with dermoscopy, distinct FFs appeared as well-demarcated areas of pallor with central follicular openings in 13 of 15 FF-bearing patients (86.7%); however, those manifestations were not recognized for TD. Conclusions Skin lesions appear to be more prevalent than previously reported (<30% vs.73.9%) in Japanese BHDS patients. Dermoscopy is a useful diagnostic aid for finding FFs. [ABSTRACT FROM AUTHOR]

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant inherited disease caused by a germline mutation in the folliculin gene mapped in the region of chromosome 17p11.2. BHD predisposes the patient to cutaneous fibrofolliculomas (FFs), pulmonary cysts (PCs), and renal cell carcinoma (RC). Here, we present two cases of BHD in Japanese patients. One patient was a 37-year-old female, and the other a 35-year-old male. Each of the patients was affected by all three symptoms of BHD. Both patients had unremarkable FFs, asymptomatic PCs, and asymptomatic RC. The presence of RC was revealed by abdominal ultrasonic examination. We also summarized the data from 62 Asian cases of BHD from the available literature and found that their FFs were unremarkable. In addition, the proportion of BHD patients with FF is smaller for Asian patients than it is for Caucasian patients. We also found that it is rare for BHD patients in Asia to show all three symptoms of BHD. Careful inspection of the skin as well as skin biopsies are important for the early detection of BHD cases in Asia.

Fibrofolliculomas are benign connective tissue tumours of the hair follicle that typically present as multiple lesions over the head and neck. A solitary fibrofolliculoma is a rare entity and has not been previously described in the canthal region. The authors report an unusual case of a 43-year-old female who was found to have a solitary fibrofolliculoma located in close proximity to the medial canthus following an excision biopsy. Whilst rare, fibrofolliculomas should be considered in the differential diagnosis of an eyelid lesion., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sonsale et al.)

Background: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant inherited syndrome caused by mutations in the folliculin coding gene (FLCN). The clinical manifestations of the syndrome involve the skin, lungs, and kidneys. Because of the rarity of the syndrome, guidelines for diagnosis and management of the patients with BHDS are lacking. Objective: To present a case story and a review of the literature on BHDS in order to give an update on genetics, clinical manifestations, diagnosis, treatment, prognosis and follow-up strategies. Design: Literature review and case story. Results: A PubMed and Embase search identified 330 papers. BHDS is characterized by small benign tumors in the skin, spontaneous pneumothoraces caused by cysts in the lungs and a seven-fold increased risk of renal cancer. A case story of a young female patient presenting with pneumothorax and a family history of recurrent pneumothoraces in many relatives illustrates how the history and the diagnostic work up resulted in a diagnosis of BHDS. Conclusion: BHDS is a rare inherited disorder. In patients with spontaneous pneumothorax or cystic lung disease without any obvious explanation, BHDS should be considered. Concomitant skin manifestations, a family history of familiar pneumothorax, renal cancers and skin manifestations supports the suspicion of BHDS. Early diagnosis is important in order to subject patients to systematic screening for renal cancers. A radiological surveillance strategy for renal cancer is proposed.

Patients with the Birt-Hogg-Dubé cancer susceptibility syndrome are at high risk of developing renal cell carcinoma, pulmonary cysts and pneumothorax, and skin lesions called fibrofolliculomas. Here we report the case of a Birt-Hogg-Dubé patient with a primary clear cell carcinoma of the thyroid (a very rare type of thyroid cancer), and FLCN loss of heterozygosity within the tumour, providing molecular evidence for this association. Our findings expand the tumour spectrum associated with this syndrome. It is paramount to identify individuals with Birt-Hogg-Dubé so that they, and subsequently their affected relatives, can benefit from tailored cancer screening and prevention.

Copyright of Bezmialem Science is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Birt-Hogg-Dubé Syndrome (BHDS) is characterized by hair follicle hamartomas, renal tumors, and pulmonary cysts. In this case series, CT findings of two index patients with BHDS, and their family members, are presented. Differential diagnosis with other cystic lung diseases is discussed. The importance of follow-up and screening for the early detection of possible malignancies, as well as multidisciplinary approach, is emphasized. The course of BHDS requires not only annual patient follow-up but also care due to the risk of pneumothorax. [ABSTRACT FROM AUTHOR]

Since the hallmark dermatologic features of Birt-Hogg-Dubé (BHD) syndrome were first described by three Canadian physicians in 1977, the clinical manifestations of BHD have been expanded to include hamartomas of the hair follicle, lung cysts, increased risk for spontaneous pneumothorax and kidney neoplasia. Twenty-five years later the causative gene FLCN was identified, and the mutation spectrum has now been defined to include mainly protein truncating mutations, but also rare missense mutations and large gene deletions/duplication. Second 'hit' FLCN mutations in BHD kidney tumors and loss of tumorigenic potential of the FLCN-null UOK257 tumor cell line when FLCN is re-expressed underscore a tumor suppressor role for FLCN. The identification of novel FLCN interacting proteins FNIP1 and FNIP2/L and their interaction with 5′-AMP activated protein kinase (AMPK) has provided a link between FLCN and the AMPK-mTOR axis and suggested molecular targets for therapeutic intervention to treat BHD kidney cancer and fibrofolliculomas. The generation of FLCN-null cell lines and in vivo animal models in which FLCN (or FNIP1) has been inactivated have provided critical reagents to facilitate mechanistic studies of FLCN function. Research efforts utilizing these critical FLCN-deficient cell lines and mice have begun to uncover important signaling pathways in which FLCN and its protein partners may play a role, including TGF-β signaling, TFE3 transcriptional regulation, PGC1-α driven mitochondrial biogenesis, apoptotic response to cell stress, and vesicular transport. As the mechanisms by which FLCN inactivation leads to BHD manifestations are clarified, we can begin to develop therapeutic agents that target the pathways dysregulated in FLCN-deficient fibrofolliculomas and kidney tumors, providing improved prognosis and quality of life for BHD patients. [ABSTRACT FROM AUTHOR]

Birt-Hogg-Dubé syndrome (MIM #135150) is characterized by the development of benign skin tumours called fibrofolliculomas, pulmonary cysts that may lead to pneumothorax and a high risk of developing kidney cancer. BHD is caused by mutations affecting the highly conserved protein folliculin (FLCN), which probably has a role in intracellular transport. Most of the research effort directed towards BHD has focused on understanding how loss of FLCN causes kidney cancer. The cutaneous manifestations have received comparatively little attention. Although understandable, it is unfortunate, as the fibrofolliculomas are highly accessible and thus potentially are an excellent system for trying to understand the basic pathobiology of BHD. Also, patients can be very much burdened by the cosmetic consequences of having hundreds of facial skin tumours. Our lack of insight into what drives fibrofolliculoma growth translates into a very limited therapeutic arsenal. Thus, paying attention to fibrofolliculomas has both basic science and practical benefits. In this review, we will discuss the state of the art regarding our understanding of fibrofolliculoma pathogenesis and indicate future directions for research. [ABSTRACT FROM AUTHOR]