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Michael T. Collins - One of the best experts on this subject based on the ideXlab platform.
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optic disc edema in patients with fibrous dysplasia mccune Albright Syndrome craniomorphometric analysis and peripapillary retinal nerve fiber layer data
Data in Brief, 2021Co-Authors: Layne N Raborn, Michael T. Collins, Kristen S Pan, Edmond J Fitzgibbon, Alison M. BoyceAbstract:Abstract This article reports quantitative measurements of intracranial volume, optic canal area, and peripapillary retinal nerve fiber layer (RNFL) for a cohort of 124 patients with craniofacial fibrous dysplasia/McCune-Albright Syndrome (FD/MAS), previously used to determine risks for developing optic disc edema [1] . Of these, 7 subjects were diagnosed with optic disc edema. OSIRIX imaging analysis software was used to collect intracranial volume and optic canal diameter for 107 patients, via 3D multiplanar reconstruction (MPR) of ≤5 mm axial CT slices. Spectral-domain Optical Coherence Tomography (OCT) was performed with the Cirrus-HD OCT (Carl Zeiss Meditec, Inc., Dublin, CA). The Optic Disc Cube 200 × 200 protocol was used for acquisition and analysis of the RNFL for 69 patients. The data can be used to assess typical ranges for intracranial volume, optic canal area, and RNFL in the craniofacial FD/MAS population and to assess ranges concerning for optic disc edema. [1] Raborn LN, Pan KS, FitzGibbon EJ, Collins MT, Boyce AM. Optic disc edema in fibrous dysplasia/McCune-Albright Syndrome: Prevalence, etiologies, and clinical implications. Bone. 2021 Feb;143:115661. doi: 10.1016/j.bone.2020.115661. Epub 2020 Sep 24. PMID: 32979536 .
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genotype phenotype correlation in fibrous dysplasia mccune Albright Syndrome
The Journal of Clinical Endocrinology and Metabolism, 2021Co-Authors: Maria Zhadina, Michael T. Collins, Kelly L Roszko, Raya E S Geels, Luis F De Castro, Alison M. BoyceAbstract:CONTEXT Fibrous dysplasia/McCune-Albright Syndrome (FD/MAS) is a rare bone and endocrine disorder resulting in fractures, pain, and disability. There are no targeted or effective therapies to alter the disease course. Disease arises from somatic gain-of-function variants at the R201 codon in GNAS, replacing arginine by either cysteine or histidine. The relative pathogenicity of these variants is not fully understood. OBJECTIVE This work aimed 1) to determine whether the most common GNAS variants (R201C and R201H) are associated with a specific clinical phenotype, and 2) to determine the prevalence of the most common GNAS variants in a large patient cohort. METHODS This retrospective cross-sectional analysis measured the correlation between genotype and phenotype characterized by clinical, biochemical, and radiographic data. RESULTS Sixty-one individuals were genotyped using DNA extracted from tissue or circulating cell-free DNA. Twenty-two patients (36.1%) had the R201C variant, and 39 (63.9%) had the R201H variant. FD skeletal disease burden, hypophosphatemia prevalence, fracture incidence, and ambulation status were similar between the 2 groups. There was no difference in the prevalence of endocrinopathies, ultrasonographic gonadal or thyroid abnormalities, or pancreatic involvement. There was a nonsignificant association of cancer with the R201H variant. CONCLUSION There is no clear genotype-phenotype correlation in patients with the most common FD/MAS pathogenic variants. The predominance of the R201H variant observed in our cohort and reported in the literature indicates it is likely responsible for a larger burden of disease in the overall population of patients with FD/MAS, which may have important implications for the future development of targeted therapies.
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genotype phenotype correlation in fibrous dysplasia mccune Albright Syndrome
The Journal of Clinical Endocrinology and Metabolism, 2021Co-Authors: Maria Zhadina, Michael T. Collins, Kelly L Roszko, Raya E S Geels, Luis F De Castro, Alison M. BoyceAbstract:CONTEXT Fibrous dysplasia/McCune-Albright Syndrome (FD/MAS) is a rare bone and endocrine disorder resulting in fractures, pain, and disability. There are no targeted or effective therapies to alter the disease course. Disease arises from somatic gain-of-function variants at the R201 codon in GNAS, replacing arginine by either cysteine or histidine. The relative pathogenicity of these variants is not fully understood. OBJECTIVE 1) To determine whether the most common GNAS variants (R201C and R201H) are associated with a specific clinical phenotype, and 2) to determine the prevalence of the most common GNAS variants in a large patient cohort. DESIGN Retrospective cross-sectional analysis. MAIN OUTCOME MEASURES Correlation between genotype and phenotype characterized by clinical, biochemical, and radiographic data. RESULTS Sixty-one subjects were genotyped using DNA extracted from tissue or circulating cell-free DNA. Twenty-two subjects (36.1%) had the R201C variant, and 39 (63.9%) had the R201H variant. FD skeletal disease burden, hypophosphatemia prevalence, fracture incidence, and ambulation status were similar between the two groups. There was no difference in the prevalence of endocrinopathies, ultrasonographic gonadal or thyroid abnormalities, or pancreatic involvement. There was a non-significant association of cancer with the R201H variant. CONCLUSION There is no clear genotype-phenotype correlation in patients with the most common FD/MAS pathogenic variants. The predominance of the R201H variant observed in our cohort and reported in the literature indicates it is likely responsible for a larger burden of disease in the overall population of patients with FD/MAS, which may have important implications for future development of targeted therapies.
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the clinical spectrum of mccune Albright Syndrome and its management
Hormone Research in Paediatrics, 2019Co-Authors: Tiahna Spencer, Kristen S Pan, Michael T. Collins, Alison M. BoyceAbstract:McCune-Albright Syndrome (MAS) is a rare, mosaic disorder presenting along a broad clinical spectrum. Disease arises from somatic-activating GNAS mutations, leading to constitutive Gαs activation and ligand-independent signaling of the Gαs-coupled protein receptor. The phenotype is largely determined by location and extent of tissues in which the GNAS mutation is expressed, as well as the pathophysiologic effects of Gαs activation within these tissues. Patients pre-sent clinically with a variable combination of fibrous dysplasia of bone (FD), cafe-au-lait skin macules, and hyperfunctioning endocrinopathies. In bone, Gαs leads to impaired differentiation of skeletal stem cells and formation of discrete, expansile FD lesions, resulting in fractures, pain, and functional impairment. A systematic approach to diagnosis and management is critically important to optimize outcomes for patients with FD/MAS. There are no medical therapies capable of altering the disease course in FD; however, screening and treatment for endocrinopathies can mitigate some skeletal morbidities. This review summarizes current understanding of MAS pathophysiology, describes the spectrum of clinical features, and includes a detailed discussion of the recommended approach to diagnosis and management.
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Gynecologic and reproductive outcomes in fibrous dysplasia/McCune-Albright Syndrome
BMC, 2019Co-Authors: Alison M. Boyce, Rachel K Casey, Diana Ovejero Crespo, Cynthia M Murdock, Andrea Estrada, Lori C Guthrie, Beth A Brillante, L K Nieman, Veronica Gomez-lobo, Michael T. CollinsAbstract:Abstract Background Autonomous ovarian activation with recurrent estrogen-producing cysts is a hallmark feature of the rare bone and endocrine disorder fibrous dysplasia/McCune-Albright Syndrome. Precocious puberty in girls with McCune-Albright Syndrome has been well-described, however long-term effects on gynecologic and reproductive function are unknown. Concerningly, case reports have described poor skeletal outcomes associated with pregnancy in women with fibrous dysplasia. Methods Thirty-nine women with fibrous dysplasia/McCune-Albright Syndrome were evaluated as part of a natural history study. Clinical, radiographic, and biochemical data were reviewed. Women were contacted to obtain detailed menstrual and reproductive histories. Results Abnormal uterine bleeding affected 77% of women (30/39), and was associated with severe anemia requiring blood transfusion in 3 cases. Nine women underwent hysterectomy for management of bleeding, including 67% (6/9) at the unusually young age of less than age 35 years. Infertility affected 43% of women (9/21), including 2 women who developed primary ovarian insufficiency after undergoing surgical treatment of ovarian cysts. Of 25 spontaneous pregnancies in 14 women, 35% (8) were unplanned. Among the 14 pregnancies, pregnancy was associated with no change in bone pain in 7 subjects (53%), increased bone pain in 4 subjects (31%), and decreased bone pain in 2 subjects (15%). No additional skeletal complications were reported during pregnancies. Conclusions Women with fibrous dysplasia/McCune-Albright Syndrome report a high prevalence of gynecologic morbidity and reduced fertility. There is no clear association between pregnancy and poor skeletal outcomes in this population
Alison M. Boyce - One of the best experts on this subject based on the ideXlab platform.
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optic disc edema in patients with fibrous dysplasia mccune Albright Syndrome craniomorphometric analysis and peripapillary retinal nerve fiber layer data
Data in Brief, 2021Co-Authors: Layne N Raborn, Michael T. Collins, Kristen S Pan, Edmond J Fitzgibbon, Alison M. BoyceAbstract:Abstract This article reports quantitative measurements of intracranial volume, optic canal area, and peripapillary retinal nerve fiber layer (RNFL) for a cohort of 124 patients with craniofacial fibrous dysplasia/McCune-Albright Syndrome (FD/MAS), previously used to determine risks for developing optic disc edema [1] . Of these, 7 subjects were diagnosed with optic disc edema. OSIRIX imaging analysis software was used to collect intracranial volume and optic canal diameter for 107 patients, via 3D multiplanar reconstruction (MPR) of ≤5 mm axial CT slices. Spectral-domain Optical Coherence Tomography (OCT) was performed with the Cirrus-HD OCT (Carl Zeiss Meditec, Inc., Dublin, CA). The Optic Disc Cube 200 × 200 protocol was used for acquisition and analysis of the RNFL for 69 patients. The data can be used to assess typical ranges for intracranial volume, optic canal area, and RNFL in the craniofacial FD/MAS population and to assess ranges concerning for optic disc edema. [1] Raborn LN, Pan KS, FitzGibbon EJ, Collins MT, Boyce AM. Optic disc edema in fibrous dysplasia/McCune-Albright Syndrome: Prevalence, etiologies, and clinical implications. Bone. 2021 Feb;143:115661. doi: 10.1016/j.bone.2020.115661. Epub 2020 Sep 24. PMID: 32979536 .
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genotype phenotype correlation in fibrous dysplasia mccune Albright Syndrome
The Journal of Clinical Endocrinology and Metabolism, 2021Co-Authors: Maria Zhadina, Michael T. Collins, Kelly L Roszko, Raya E S Geels, Luis F De Castro, Alison M. BoyceAbstract:CONTEXT Fibrous dysplasia/McCune-Albright Syndrome (FD/MAS) is a rare bone and endocrine disorder resulting in fractures, pain, and disability. There are no targeted or effective therapies to alter the disease course. Disease arises from somatic gain-of-function variants at the R201 codon in GNAS, replacing arginine by either cysteine or histidine. The relative pathogenicity of these variants is not fully understood. OBJECTIVE This work aimed 1) to determine whether the most common GNAS variants (R201C and R201H) are associated with a specific clinical phenotype, and 2) to determine the prevalence of the most common GNAS variants in a large patient cohort. METHODS This retrospective cross-sectional analysis measured the correlation between genotype and phenotype characterized by clinical, biochemical, and radiographic data. RESULTS Sixty-one individuals were genotyped using DNA extracted from tissue or circulating cell-free DNA. Twenty-two patients (36.1%) had the R201C variant, and 39 (63.9%) had the R201H variant. FD skeletal disease burden, hypophosphatemia prevalence, fracture incidence, and ambulation status were similar between the 2 groups. There was no difference in the prevalence of endocrinopathies, ultrasonographic gonadal or thyroid abnormalities, or pancreatic involvement. There was a nonsignificant association of cancer with the R201H variant. CONCLUSION There is no clear genotype-phenotype correlation in patients with the most common FD/MAS pathogenic variants. The predominance of the R201H variant observed in our cohort and reported in the literature indicates it is likely responsible for a larger burden of disease in the overall population of patients with FD/MAS, which may have important implications for the future development of targeted therapies.
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genotype phenotype correlation in fibrous dysplasia mccune Albright Syndrome
The Journal of Clinical Endocrinology and Metabolism, 2021Co-Authors: Maria Zhadina, Michael T. Collins, Kelly L Roszko, Raya E S Geels, Luis F De Castro, Alison M. BoyceAbstract:CONTEXT Fibrous dysplasia/McCune-Albright Syndrome (FD/MAS) is a rare bone and endocrine disorder resulting in fractures, pain, and disability. There are no targeted or effective therapies to alter the disease course. Disease arises from somatic gain-of-function variants at the R201 codon in GNAS, replacing arginine by either cysteine or histidine. The relative pathogenicity of these variants is not fully understood. OBJECTIVE 1) To determine whether the most common GNAS variants (R201C and R201H) are associated with a specific clinical phenotype, and 2) to determine the prevalence of the most common GNAS variants in a large patient cohort. DESIGN Retrospective cross-sectional analysis. MAIN OUTCOME MEASURES Correlation between genotype and phenotype characterized by clinical, biochemical, and radiographic data. RESULTS Sixty-one subjects were genotyped using DNA extracted from tissue or circulating cell-free DNA. Twenty-two subjects (36.1%) had the R201C variant, and 39 (63.9%) had the R201H variant. FD skeletal disease burden, hypophosphatemia prevalence, fracture incidence, and ambulation status were similar between the two groups. There was no difference in the prevalence of endocrinopathies, ultrasonographic gonadal or thyroid abnormalities, or pancreatic involvement. There was a non-significant association of cancer with the R201H variant. CONCLUSION There is no clear genotype-phenotype correlation in patients with the most common FD/MAS pathogenic variants. The predominance of the R201H variant observed in our cohort and reported in the literature indicates it is likely responsible for a larger burden of disease in the overall population of patients with FD/MAS, which may have important implications for future development of targeted therapies.
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the clinical spectrum of mccune Albright Syndrome and its management
Hormone Research in Paediatrics, 2019Co-Authors: Tiahna Spencer, Kristen S Pan, Michael T. Collins, Alison M. BoyceAbstract:McCune-Albright Syndrome (MAS) is a rare, mosaic disorder presenting along a broad clinical spectrum. Disease arises from somatic-activating GNAS mutations, leading to constitutive Gαs activation and ligand-independent signaling of the Gαs-coupled protein receptor. The phenotype is largely determined by location and extent of tissues in which the GNAS mutation is expressed, as well as the pathophysiologic effects of Gαs activation within these tissues. Patients pre-sent clinically with a variable combination of fibrous dysplasia of bone (FD), cafe-au-lait skin macules, and hyperfunctioning endocrinopathies. In bone, Gαs leads to impaired differentiation of skeletal stem cells and formation of discrete, expansile FD lesions, resulting in fractures, pain, and functional impairment. A systematic approach to diagnosis and management is critically important to optimize outcomes for patients with FD/MAS. There are no medical therapies capable of altering the disease course in FD; however, screening and treatment for endocrinopathies can mitigate some skeletal morbidities. This review summarizes current understanding of MAS pathophysiology, describes the spectrum of clinical features, and includes a detailed discussion of the recommended approach to diagnosis and management.
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gynecologic and reproductive outcomes in fibrous dysplasia mccune Albright Syndrome
Orphanet Journal of Rare Diseases, 2019Co-Authors: Alison M. Boyce, Rachel K Casey, Diana Ovejero Crespo, Cynthia M Murdock, Andrea Estrada, Lori C Guthrie, Beth A Brillante, Veronica Gomezlobo, L K NiemanAbstract:Background Autonomous ovarian activation with recurrent estrogen-producing cysts is a hallmark feature of the rare bone and endocrine disorder fibrous dysplasia/McCune-Albright Syndrome. Precocious puberty in girls with McCune-Albright Syndrome has been well-described, however long-term effects on gynecologic and reproductive function are unknown. Concerningly, case reports have described poor skeletal outcomes associated with pregnancy in women with fibrous dysplasia.
Margaret Zacharin - One of the best experts on this subject based on the ideXlab platform.
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SHORT REPORT Gastrointestinal polyps in McCune Albright Syndrome
2016Co-Authors: Margaret Zacharin, Anurag Bajpai, C W Chow, Michelle W Wong, Anthony Catto-smith, Constantine Stratakis, Rodney ScottAbstract:Background McCune Albright Syndrome (MAS), a disorder caused by somatic activating mutations in the GNAS gene, usually presents with cutaneous, skeletal, and endocrine manifestations. While focal lesions involving multiple tissues have been identified in MAS, almost nothing is known about gastrointestinal lesions in this disease. Methods Two MAS patients with perioral freckling, resembling PeutzeJeghers Syndrome (PJS), and two MAS patients without similar pigmentation underwent gastrointestinal endoscopy to establish if they had coexisting hamartomatous polyposis. Three of 4 subjects had documented GNAS mutations in peripheral blood. Genetic testing for STK11 and PRKAR1A genes was performed to exclude presence of coexistent PJS and Carney complex. Genetic testing of biopsy material was also performed. Results Hamartomatous gastrointestinal polyps with histological features similar to those in PJS were observed in all 4 subjects, only in the stomach and/or upper duodenum. Activating GNAS mutations were found in the polyps or adjacent mucosa in 3 of 4 subjects. One patient each had mutation only in the blood or tissue, while 2 patients had both. No subject harboured any detectable PRKARIA or STK11 mutation as determined by direct DNA sequencing and copy number variation analysis. Conclusions These findings confirm that gastrointestinal polyps are a common manifestation of MAS, indicate an overlap between MAS and PJS, and point towards a putative interaction between the GNAS and STK11 genes in the pathogenesis of these two disorders. The findings suggest a need for routine gastrointestinal endoscopy in patients with MAS, to establish the true incidence of polyps in these patients
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gastrointestinal polyps in mccune Albright Syndrome
Journal of Medical Genetics, 2011Co-Authors: Margaret Zacharin, Anurag Bajpai, Constantine A Stratakis, C W Chow, Anthony G Cattosmith, Michelle W Wong, Rodney J ScottAbstract:Background McCune Albright Syndrome (MAS), a disorder caused by somatic activating mutations in the GNAS gene, usually presents with cutaneous, skeletal, and endocrine manifestations. While focal lesions involving multiple tissues have been identified in MAS, almost nothing is known about gastrointestinal lesions in this disease. Methods Two MAS patients with perioral freckling, resembling Peutz-Jeghers Syndrome (PJS), and two MAS patients without similar pigmentation underwent gastrointestinal endoscopy to establish if they had coexisting hamartomatous polyposis. Three of 4 subjects had documented GNAS mutations in peripheral blood. Genetic testing for STK11 and PRKAR1A genes was performed to exclude presence of coexistent PJS and Carney complex. Genetic testing of biopsy material was also performed. Results Hamartomatous gastrointestinal polyps with histological features similar to those in PJS were observed in all 4 subjects, only in the stomach and/or upper duodenum. Activating GNAS mutations were found in the polyps or adjacent mucosa in 3 of 4 subjects. One patient each had mutation only in the blood or tissue, while 2 patients had both. No subject harboured any detectable PRKARIA or STK11 mutation as determined by direct DNA sequencing and copy number variation analysis. Conclusions These findings confirm that gastrointestinal polyps are a common manifestation of MAS, indicate an overlap between MAS and PJS, and point towards a putative interaction between the GNAS and STK11 genes in the pathogenesis of these two disorders. The findings suggest a need for routine gastrointestinal endoscopy in patients with MAS, to establish the true incidence of polyps in these patients.
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platelet dysfunction and increased bleeding tendency in mccune Albright Syndrome
The Journal of Pediatrics, 2008Co-Authors: Anurag Bajpai, Anthea Greenway, Margaret ZacharinAbstract:We observed increased bleeding tendency and platelet function abnormalities in 3 boys with McCune-Albright Syndrome (MAS). We speculate that platelet dysfunction contributed to excessive blood loss in our patients. This report of platelet dysfunction in MAS highlights the need for assessment of platelet functions in the condition.
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Intramedullary rodding and bisphosphonate treatment of polyostotic fibrous dysplasia associated with the McCune-Albright Syndrome.
Journal of pediatric orthopedics, 2002Co-Authors: Mark O’sullivan, Margaret ZacharinAbstract:The authors report the results of the management of five consecutive children with McCune-Albright Syndrome. These children were treated with a combination of drug treatment (bisphosphonates) and surgical treatment with elongating intramedullary rods (Sheffield) for management of femoral and tibial lesions. This treatment was successful in all patients, as judged by improvement in their quality of life and in clinical parameters, such as decreased bone pain and fracture rate, and improved walking ability. Two of the five children had been wheelchair-bound before treatment. All children are now community ambulators. In 5 of 10 hips, there was a significant decrease in the neck-shaft angle over time compared with the immediate postoperative angle.
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intravenous pamidronate treatment of polyostotic fibrous dysplasia associated with the mccune Albright Syndrome
The Journal of Pediatrics, 2000Co-Authors: Margaret Zacharin, Mark OsullivanAbstract:Abstract Objectives: An open trial of pamidronate treatment was undertaken in 5 children and 4 young adults with polyostotic fibrous dysplasia associated with McCune Albright Syndrome to assess clinical response, bone turnover, and cardiovascular status over a 2-year period. Study design: Pamidronate was administered by intravenous infusion 1 mg/kg/d for 3 days every 6 months for 2 years. Bone turnover was measured at 0, 6, 12, 18, and 24 months with bone mineral density, and cardiac output was assessed by echocardiography at 0, 12, and 24 months. Results: All subjects reported marked reduction in bone pain and sustained increased mobility. The fracture rate decreased in most. Orthopedic insertion of intramedullary rods was successful with maintenance of rod position. Mean osteocalcin levels fell from 35.5 ± 5.6 μg/L to 28.4 ± 4.1 μg/L ( P 2 ( P 2 in adults ( P Conclusions: Pamidronate treatment is an effective therapeutic modality for children with polyostotic fibrous dysplasia, with a good short-term safety profile. Failure to demonstrate major biochemical or bone densitometry improvements is due to the nature of the fibrous dysplasia and intercurrent microfracture. (J Pediatr 2000;137:403-9)
Anne Barlier - One of the best experts on this subject based on the ideXlab platform.
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using digital droplet polymerase chain reaction to detect the mosaic gnas mutations in whole blood dna or circulating cell free dna in fibrous dysplasia and mccune Albright Syndrome
The Journal of Pediatrics, 2019Co-Authors: Pauline Romanet, Francoise Paris, Pascal Philibert, Frederic Fina, Thomas Cuny, Catherine Roche, Lhoucine Ouafik, Rachel Reynaud, Anne BarlierAbstract:The GNAS postzygotic mosaic activating mutations involved in fibrous dysplasia and McCune-Albright Syndrome (MAS) are not detectable in leukocytes by Sanger sequencing. Digital droplet polymerase chain reaction detects GNAS mutations in 7 of 12 patients (58.3%) suspected to have fibrous dysplasia/MAS from whole blood DNA, and in 4 of 5 patients (80%) from circulating cell-free DNA.
Erica A. Eugster - One of the best experts on this subject based on the ideXlab platform.
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fulvestrant treatment of precocious puberty in girls with mccune Albright Syndrome
International Journal of Pediatric Endocrinology, 2012Co-Authors: Emily K Sims, Charles Sultan, Sally Garnett, Franco Guzman, Francoise Paris, Erica A. EugsterAbstract:McCune-Albright Syndrome (MAS) is usually characterized by the triad of precocious puberty (PP), fibrous dysplasia, and cafe au lait spots. Previous treatments investigated for PP have included aromatase inhibitors and the estrogen receptor modulator, tamoxifen. Although some agents have been partially effective, the optimal pharmacologic treatment of PP in girls with MAS has not been identified. The objective of this study was to evaluate the safety and efficacy of fulvestrant (FaslodexTM), a pure estrogen receptor antagonist, in girls with progressive precocious puberty (PP) associated with McCune-Albright Syndrome (MAS). In this prospective international multicenter trial, thirty girls ≤ 10 years old with MAS and progressive PP received fulvestrant 4 mg/kg via monthly intramuscular injections for 12 months. Changes in vaginal bleeding, rates of bone age advancement, growth velocity, Tanner staging, predicted adult heights, and uterine and ovarian volumes were measured. Median vaginal bleeding days decreased from 12.0 days per year to 1.0 day per year, with a median change in frequency of -3.6 days, (95% confidence interval (CI) -10.10, 0.00; p = 0.0146). Of patients with baseline bleeding, 74% experienced a ≥50% reduction in bleeding, and 35% experienced complete cessation during the study period (95% CI 51.6%, 89.8%; 16.4%, 57.3%, respectively). Average rates of bone age advancement (ΔBA/ΔCA) decreased from 1.99 pre-treatment to 1.06 on treatment (mean change -0.93, 95% CI -1.43, -0.43; p = 0.0007). No significant changes in uterine volumes or other endpoints or serious adverse events occurred. Fulvestrant was well tolerated and moderately effective in decreasing vaginal bleeding and rates of skeletal maturation in girls with MAS. Longer-term studies aimed at further defining potential benefits and risks of this novel therapeutic approach in girls with MAS are needed. NCT00278915
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mccune Albright Syndrome and the extraskeletal manifestations of fibrous dysplasia
Orphanet Journal of Rare Diseases, 2012Co-Authors: Michael T. Collins, Frederick R Singer, Erica A. EugsterAbstract:Fibrous dysplasia (FD) is sometimes accompanied by extraskeletal manifestations that can include any combination of cafe-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing Syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright Syndrome (MAS). The broad spectrum of involved tissues and the unpredictable combination of findings owe to the fact that molecular defect is due to dominant activating mutations in the widely expressed signaling protein, Gsα, and the fact these mutations arises sporadically, often times early in development, prior to gastrulation, and can distribute across many or few tissues.
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mccune Albright Syndrome and the extraskeletal manifestations of fibrous dysplasia
Orphanet Journal of Rare Diseases, 2012Co-Authors: Michael T. Collins, Frederick R Singer, Erica A. EugsterAbstract:Fibrous dysplasia (FD) is sometimes accompanied by extraskeletal manifestations that can include any combination of cafe-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing Syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright Syndrome (MAS). The broad spectrum of involved tissues and the unpredictable combination of findings owe to the fact that molecular defect is due to dominant activating mutations in the widely expressed signaling protein, Gsα, and the fact these mutations arises sporadically, often times early in development, prior to gastrulation, and can distribute across many or few tissues. The complexity can be mastered by a systematic screening of potentially involved tissues and cognizance that the pattern of involved tissues is established, to some degree, in utero. Thorough testing allows the clinician to establish, often times at presentation, the full extent of the disease, and importantly as well what tissues are unaffected. Treatment and follow-up can then be focused on affected systems and a meaningful prognosis can be offered to the patient and family. The authors outline screening and treatment strategies that allow for effective management of the extraskeletal manifestations of FD.
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oophorectomy in mccune Albright Syndrome a case of mistaken identity
Journal of Pediatric Surgery, 2007Co-Authors: Zeina M Nabhan, Karen W West, Erica A. EugsterAbstract:Abstract Objective The objective of the study was to determine the incidence of oophorectomy in girls presenting with precocious puberty and vaginal bleeding who are subsequently diagnosed with McCune-Albright Syndrome (MAS). Study Design Medical records of girls diagnosed with MAS between 1988 and 2005 were reviewed. Variables analyzed included presenting features, presence of cafe au lait macules, presence of fibrous dysplasia, radiographic studies, estradiol levels, tumor markers, surgery, and pathology reports. Results Nine girls with MAS were identified. Average age at initial presentation was 3.2 ± 2.1 years (range, 0.6-7 years). All patients presented with sudden onset of vaginal bleeding. Eight (88%) also had breast development and 2 (22%) had associated pubic hair. Four (44%) girls underwent salpingo-oophorectomy before the diagnosis of MAS was made. Of these, 3 had cafe au lait macules on initial presentation, and 3 were later diagnosed with fibrous dysplasia. Surgical pathology revealed benign ovarian cysts in all 4 patients. Conclusion Unnecessary oophorectomy is common in girls with MAS who are taken to the operating room for a presumed ovarian tumor. This highlights the need for increased awareness of MAS among pediatricians, pediatric surgeons, and emergency room physicians. Distinguishing features, which can be helpful in differentiating these 2 conditions, are often present.
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treatment of precocious puberty in mccune Albright Syndrome
Pediatric endocrinology reviews, 2007Co-Authors: Jakub Mieszczak, Erica A. EugsterAbstract:McCune-Albright Syndrome (MAS) is typically defined as a triad of precocious puberty (PP), cafe au lait spots and fibrous dysplasia of bone. PP is the most common endocrinological manifestation of this rare disease and is much more common in girls than in boys. The treatment options for PP associated with MAS have evolved over the last twenty plus years. Therapy in girls typically includes the use of an anti-estrogen, while treatment options in boys include an antiandrogen in combination with an aromatase inhibitor (AI). This article will briefly review the older therapies and explain why they have largely been supplanted by newer approaches. We will discuss current pharmacotherapy options for the treatment of PP in MAS and finally describe potential novel therapies that will hopefully enable optimal care for affected patients.