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Maurice A.m. Van Steensel - One of the best experts on this subject based on the ideXlab platform.
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dube ́ Syndrome: A Double-Blind Placebo- Controlled Randomized Split-Face Trial
2016Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract:Background: Birt-Hogg-Dube ́ 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. Methods: We 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. Results: No change in cosmetic status of Fibrofolliculomas was reported in the majority of cases for the rapamycin treate
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial
PloS one, 2014Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Herm Martens, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract:Background Birt-Hogg-Dube 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.
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial
2014Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Herm Martens, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract: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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Birt–Hogg–Dubé syndrome and the skin
Familial cancer, 2013Co-Authors: Marigje Vernooij, Tijs Claessens, Monique Luijten, Maurice A.m. Van Steensel, Barry J. CoullAbstract:Birt-Hogg-Dube 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.
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Original ArticleNovel Mutations in the BHD Gene and Absence of Loss of Heterozygosity in Fibrofolliculomas of Birt-Hogg-Dubé Patients
The Journal of investigative dermatology, 2006Co-Authors: Maurice A.m. Van Steensel, Valerie L. R. M. Verstraeten, Jorge Frank, Nicole W.j. Kelleners-smeets, Pamela Poblete-gutiérrez, D. Marcus-soekarman, Reno S. Bladergroen, Peter M. Steijlen, Michel Van GeelAbstract:Birt-Hogg-Dube (BHD) syndrome is an autosomal-dominantly inherited cancer syndrome characterized by Fibrofolliculomas, lung cysts leading to pneumothorax, and chromophobic/oncocytic renal cell carcinoma. The disease is caused by heterozygous mutations in the BHD gene encoding folliculin and all mutations reported putatively lead to protein truncation. Although the function of folliculin is unknown, it is thought to be a tumor suppressor, with loss of heterozygosity (LOH) initiating tumor formation. Here, we report on four novel BHD gene mutations, including two splice-site mutations, in patients presenting with skin lesions only. We further show that LOH cannot be detected in Fibrofolliculomas from three patients, suggesting that for the manifestation of cutaneous tumors in BHD syndrome haplo-insufficiency of folliculin is sufficient to initiate uncontrolled growth. Renal microscopic oncocytosis in BHD is considered as a precursor to malignant kidney tumors and may likewise be the result of haplo-insufficiency, with somatic second-hit mutations or LOH giving rise to malignancy later in life.
Marigje Vernooij - One of the best experts on this subject based on the ideXlab platform.
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dube ́ Syndrome: A Double-Blind Placebo- Controlled Randomized Split-Face Trial
2016Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract:Background: Birt-Hogg-Dube ́ 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. Methods: We 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. Results: No change in cosmetic status of Fibrofolliculomas was reported in the majority of cases for the rapamycin treate
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial
PloS one, 2014Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Herm Martens, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract:Background Birt-Hogg-Dube 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.
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial
2014Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Herm Martens, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract: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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Birt–Hogg–Dubé syndrome and the skin
Familial Cancer, 2013Co-Authors: Marigje Vernooij, Tijs Claessens, Monique Luijten, Maurice A. M. Steensel, Barry J. CoullAbstract: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.
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Birt–Hogg–Dubé syndrome and the skin
Familial cancer, 2013Co-Authors: Marigje Vernooij, Tijs Claessens, Monique Luijten, Maurice A.m. Van Steensel, Barry J. CoullAbstract:Birt-Hogg-Dube 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.
Theo M. Starink - One of the best experts on this subject based on the ideXlab platform.
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dube ́ Syndrome: A Double-Blind Placebo- Controlled Randomized Split-Face Trial
2016Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract:Background: Birt-Hogg-Dube ́ 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. Methods: We 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. Results: No change in cosmetic status of Fibrofolliculomas was reported in the majority of cases for the rapamycin treate
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial
PloS one, 2014Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Herm Martens, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract:Background Birt-Hogg-Dube 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.
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial
2014Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Herm Martens, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract: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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Familial multiple discoid fibromas: a look-alike of Birt-Hogg-Dubé syndrome not linked to the FLCN locus.
Journal of The American Academy of Dermatology, 2011Co-Authors: Theo M. Starink, Arjan C. Houweling, Martijn B.a. Van Doorn, Edward M. Leter, Elisabeth H. Jaspars, R. Jeroen A. Van Moorselaar, Piet E. Postmus, Paul C. Johannesma, Jan Hein T.m. Van Waesberghe, Martijn H. PloegerAbstract:Background Previously, we proposed that familial multiple trichodiscomas (OMIM 190340) is distinct from Birt-Hogg-Dube syndrome (BHD) (OMIM #135150). BHD is characterized by multiple Fibrofolliculomas/trichodiscomas, lung cysts, pneumothorax, and renal cell cancer. Germline FLCN mutations can be detected in most but not all BHD families. Objective We sought to evaluate familial multiple trichodiscomas at a clinical and genetic level. We now renamed this condition "familial multiple discoid fibromas" (FMDF) to emphasize the distinction from BHD. Methods In 8 additional families with an autosomal dominant pattern of multiple discoid fibromas we assessed the clinical findings and the histopathological features of skin lesions. FLCN germline mutation analysis was completed in 7 families. In two of these families segregation analysis was performed using polymorphic DNA markers in and around the FLCN locus. Results The clinical findings in FMDF are different from those in BHD with early onset of skin lesions, prominent involvement of the pinnae, and discoid fibromas without the follicular epithelial component characteristic of the Fibrofolliculoma/trichodiscoma spectrum of BHD. In addition, there were no evident pulmonary or renal complications. In none of the families were pathogenic FLCN germline mutations identified. Using segregation analysis we could exclude involvement of the FLCN locus in the two kindreds tested. Limitations The prevalence of FMDF is presently unknown. The underlying gene defect has not yet been identified. Conclusions FMDF is clinically distinct from BHD and is not linked to the FLCN locus.
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Spontaneous pneumothorax as the first manifestation of a hereditary condition with an increased renal cancer risk
Nederlands tijdschrift voor geneeskunde, 2009Co-Authors: Paul C. Johannesma, Theo M. Starink, R. Jeroen A. Van Moorselaar, Piet E. Postmus, Jan-willem J Lammers, Fred H. MenkoAbstract:Spontaneous pneumothorax can be due to Birt-Hogg-Dube syndrome (BHD syndrome), an autosomal dominant predisposition for Fibrofolliculomas, multiple lung cysts, pneumothorax and renal cancer. The syndrome is the result of germline mutations in the FLCN (folliculin) gene. Its clinical presentation is highly variable. Consequently, this syndrome is probably under-diagnosed. An illustrative kindred is presented in which the index patient, a man aged 26, had recurrent episodes of pneumothorax without apparent skin lesions or renal abnormalities. He had bilateral mostly basally-located lung cysts. There was a family history of Fibrofolliculomas, lung cysts, pneumothorax and clear cell renal cancer. Recognition of BHD is important since carriers of the mutation can be offered surveillance for early detection and treatment of renal cancer.
Lieke M. C. Gijezen - One of the best experts on this subject based on the ideXlab platform.
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dube ́ Syndrome: A Double-Blind Placebo- Controlled Randomized Split-Face Trial
2016Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract:Background: Birt-Hogg-Dube ́ 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. Methods: We 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. Results: No change in cosmetic status of Fibrofolliculomas was reported in the majority of cases for the rapamycin treate
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial
PloS one, 2014Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Herm Martens, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract:Background Birt-Hogg-Dube 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.
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial
2014Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Herm Martens, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract: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
Fred H. Menko - One of the best experts on this subject based on the ideXlab platform.
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dube ́ Syndrome: A Double-Blind Placebo- Controlled Randomized Split-Face Trial
2016Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract:Background: Birt-Hogg-Dube ́ 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. Methods: We 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. Results: No change in cosmetic status of Fibrofolliculomas was reported in the majority of cases for the rapamycin treate
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial
PloS one, 2014Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Herm Martens, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract:Background Birt-Hogg-Dube 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.
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Topical Rapamycin as a Treatment for Fibrofolliculomas in Birt-Hogg-Dubé Syndrome: A Double-Blind Placebo-Controlled Randomized Split-Face Trial
2014Co-Authors: Lieke M. C. Gijezen, Theo M. Starink, Marigje Vernooij, Herm Martens, Charlene E. U. Oduber, Charles J. M. Henquet, Martin H. Prins, Fred H. Menko, Patty J. Nelemans, Maurice A.m. Van SteenselAbstract: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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Spontaneous pneumothorax as the first manifestation of a hereditary condition with an increased renal cancer risk
Nederlands tijdschrift voor geneeskunde, 2009Co-Authors: Paul C. Johannesma, Theo M. Starink, R. Jeroen A. Van Moorselaar, Piet E. Postmus, Jan-willem J Lammers, Fred H. MenkoAbstract:Spontaneous pneumothorax can be due to Birt-Hogg-Dube syndrome (BHD syndrome), an autosomal dominant predisposition for Fibrofolliculomas, multiple lung cysts, pneumothorax and renal cancer. The syndrome is the result of germline mutations in the FLCN (folliculin) gene. Its clinical presentation is highly variable. Consequently, this syndrome is probably under-diagnosed. An illustrative kindred is presented in which the index patient, a man aged 26, had recurrent episodes of pneumothorax without apparent skin lesions or renal abnormalities. He had bilateral mostly basally-located lung cysts. There was a family history of Fibrofolliculomas, lung cysts, pneumothorax and clear cell renal cancer. Recognition of BHD is important since carriers of the mutation can be offered surveillance for early detection and treatment of renal cancer.