Pulmonary Cysts of Birt-Hogg-Dubé Syndrome

Furuya, Mitsuko; Tanaka, Reiko; Koga, Shunsuke; Yatabe, Yasushi; Gotoda, Hiroko; Takagi, Seiji; Hsu, Yung-Hsiang; Fujii, Takeshi; Okada, Akira; Moritani, Suzuko; Mizuno, Hideki; Nagashima, Yoji; Nagahama, Kiyotaka; Hiroshima, Kenzo; Yoshino, Ichiro; Nomura, Fumio; Aoki, Ichiro; Nakatani, Yukio

doi:10.1097/pas.0b013e3182475240

Cited by 93 publications

(33 citation statements)

References 29 publications

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“…This is consistent with findings of increased HIF-1a and VEGF in the lungs of BHD patients [9]. Considering that FLCN has been reported to either stimulate or suppress mammalian target of rapamycin (mTOR) signaling [10], and that mTOR is a potent modulator of HIF-1a, we consider that mutated FLCN may affect HIF-1a activation and thus contribute to vascular pathogenesis in BHD syndrome. Additionally, matrix metallopeptidase 9 (MMP-9) activity in the vessel wall may play an important role.…”

Section: Discussionsupporting

confidence: 88%

Birt–Hogg–Dubé syndrome and intracranial vascular pathologies

et al. 2015

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Birt-Hogg-Dubé syndrome, first described in 1977, is a rare autosomal dominant condition that commonly presents with skin lesions, including fibrofolliculomas and trichodiscomas; pulmonary cysts; spontaneous pneumothoraces; and renal cancer. We present the only known cases of intracranial vascular pathologies in patients with Birt-Hogg-Dubé syndrome. We present three cases (three female; age range 18-50) of intracranial vascular lesions in Birt-Hogg-Dubé patients, including two aneurysms and one arteriovenous malformation, and review one previously reported case of carotid aplasia. Due to the rarity of Birt-Hogg-Dubé syndrome and significant variations in its clinical presentation, it is difficult to assess whether or not Birt-Hogg-Dubé patients are predisposed to intracranial vascular pathologies. We hypothesize that increased transcription of hypoxia-inducible factor 1-alpha, resulting from a mutated form of the protein folliculin transcribed by the Birt-Hogg-Dubé gene, may be associated with vascular pathogenesis in Birt-Hogg-Dubé patients and thus provide a possible molecular basis for a link between these two conditions.

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Section: Discussionsupporting

confidence: 88%

Birt–Hogg–Dubé syndrome and intracranial vascular pathologies

et al. 2015

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“…[16,19,63,64] Approximately 30% of the patients will develop renal tumors which corresponds to a seven-fold increased risk. [10,16,34–36,65] The risk increases with age, and BHDS patients older than 70 years of age have a relative risk of renal cell carcinomas (RCC) of 16%.…”

Section: Resultsmentioning

confidence: 99%

Birt–Hogg–Dubé syndrome: a case report and a review of the literature

Jensen

Villumsen

Skytte

et al. 2017

European Clinical Respiratory Journal

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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.

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“…FLCN's functions are mostly unknown, although recent data suggest that it might be involved in cellular energy sensing through the mammalian target of rapamycin (mTOR) signalling pathway [13]. A considerable body of data suggests that in BHD, the mTOR pathway is activated [14]–[18]. Thus, we theorized that BHD syndrome belongs to a larger family of disorders characterized by mTOR deregulation, such as tuberous sclerosis complex (TSC) [14], [19].…”

Section: Introductionmentioning

confidence: 99%

Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial

et al. 2014

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BackgroundBirt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder characterised by the occurrence of benign, mostly facial, skin tumours called fibrofolliculomas, multiple lung cysts, spontaneous pneumothorax and an increased renal cancer risk. Current treatments for fibrofolliculomas have high rates of recurrence and carry a risk of complications. It would be desirable to have a treatment that could prevent fibrofolliculomas from growing. Animal models of BHD have previously shown deregulation of mammalian target of rapamycin (mTOR). Topical use of the mTOR inhibitor rapamycin is an effective treatment for the skin tumours (angiofibromas) in tuberous sclerosis complex, which is also characterised by mTOR deregulation. In this study we aimed to determine if topical rapamycin is also an effective treatment for fibrofolliculomas in BHD.MethodsWe performed a double blinded, randomised, facial left-right controlled trial of topical rapamycin 0.1% versus placebo in 19 BHD patients. Trial duration was 6 months. The primary outcome was cosmetic improvement as measured by doctors and patients. Changes in fibrofolliculoma number and size were also measured, as was occurrence of side effects.ResultsNo change in cosmetic status of fibrofolliculomas was reported in the majority of cases for the rapamycin treated (79% by doctors, 53% by patients) as well as the placebo treated facial sides (both 74%). No significant differences between rapamycin and placebo treated facial halves were observed (p = 1.000 for doctors opinion, p = 0.344 for patients opinion). No significant difference in fibrofolliculoma number or change in size of the fibrofolliculomas was seen after 6 months. Side effects occurred more often after rapamycin treatment (68% of patients) than after placebo (58% of patients; p = 0.625). A burning sensation, erythema, itching and dryness were most frequently reported.ConclusionsThis study provides no evidence that treatment of fibrofolliculomas with topical rapamycin in BHD results in cosmetic improvement.Trial RegistrationClinicalTrials.gov +NCT00928798

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Pulmonary Cysts of Birt-Hogg-Dubé Syndrome

Cited by 93 publications

References 29 publications

Birt–Hogg–Dubé syndrome and intracranial vascular pathologies

Birt–Hogg–Dubé syndrome and intracranial vascular pathologies

Birt–Hogg–Dubé syndrome: a case report and a review of the literature

Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial

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