Symptoma

Polyostotic Fibrous Dysplasia

McCune-Albright Syndrome

Polyostotic fibrous dysplasia (PFD) is a non-hereditary congenital and benign disease of the bone. In PFD, fibrous-like tissues with immature osteogenesis replace the normal bone. The lesions may be mono- or polyostotic. PFD is associated with bone pain and fractures due to bone fragility.

Polyostotic fibrous dysplasia (PFD) is caused by somatic activating mutations in the GNAS gene in the skeletal stem cells. This leads to the proliferation of immature osteogenic cells and replacement of the normal bone marrow with a fibro-osseous tissue. The lesions can result in deformity of the bones and fractures.

PFD may be mono- or polyostotic. Any part of the skeleton can be affected. The most commonly affected sites are the skull base and proximal parts of the femur. The femoral lesions are responsible for the most functional impairment [1] [2]. The lesions can be isolated or associated with hyperfunctioning endocrinopathies and café-au-lait skin spots called McCune-Albright syndrome [3] [4].

The spectrum of involvement in PFD ranges from two bones to 75% or more of the skeleton. In general, PFD is found in the tibia, femur, pelvic bones and the foot. Other sites may also be affected but less commonly, for example, the skull, ribs, and bones of the upper extremity. The lumbar spine, cervical spine, and clavicle are uncommonly affected.

Typical deformities observed in PFD include leg length discrepancies, rib deformities, and facial asymmetry.

The most common complication of PFD is fracture and it is detected in more than half of the cases with the polyostotic type of the disease [5]. The majority of patients (75%) with PFD have symptoms, including pain, deformities, and pathologic fractures [6].

Malignant transformation can occur but it is rare and the reported prevalence ranges from 0.4% to 4% [5]. The most common malignant tumors are chondrosarcoma, fibrosarcoma, and osteosarcoma. Most of the patients with malignancies are older than thirty years at the time of diagnosis. Generally, the craniofacial region is affected with the femur, tibia, and pelvis following. Polyostotic lesions have a higher rate of malignant transformation than monostotic lesions.

  • Precocious Puberty

    Albright's syndrome is characterized by the combination of polyostotic fibrous dysplasia, precocious puberty and café-au-lait spots. [ncbi.nlm.nih.gov]

    Clinical findings Precocious puberty, polyostotic (cystic fibrous dysplasia) spontaneous fractures at young age, café-au-lait spots on skin, ovarian cysts. [medical-dictionary.thefreedictionary.com]

    Puberty — Albright's Syndrome with Precocious Puberty — Albright-Mccune-Sternberg Syndrome — Albright-Sternberg Syndrome — Albright's Syndrome — Syndrome, Albright's — Albright's Disease of Bone [mesh.kib.ki.se]

  • Goiter

    A toxic multinodular goiter was also associated, but unique was the spontaneous normalization of the thyroid function. [ncbi.nlm.nih.gov]

    Osteodystrophia fibrosa combined with precocious puberty and exophthalmic goiter. Am. J. Dis. Child. 63: 748, 1942. CrossRef Google Scholar 5. Moldawer M., Rabin E.R. Polyostotic fibrous dysplasia with thyrotoxicosis. Arch. Intern. [link.springer.com]

    These include sexual precocity, espeCially in females (3, 4), goiter and/or hyperthyroidisr:n (4, 5), growth hormone (GH) hypersecretion (6), Cushing' disease (7) and ac-celerated skeletal growth (8). [docslide.com.br]

    The thyroid gland, a butterfly-shaped organ at the base of the neck, may become enlarged (a condition called a goiter) or develop masses called nodules. [ghr.nlm.nih.gov]

    Patients with McCune-Albright Syndrome may have other thyroid abnormalities, including thyroid enlargement (called a goiter), cysts, and nodules. [magicfoundation.org]

  • Wheelchair Bound

    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. [ncbi.nlm.nih.gov]

    A 5-point score was used: 0, bed-wheelchair-bound; 1, walking with aids possible, but nonfunctional; 2, household walker, with/without aids; 3, neighborhood walker with/without aids; and 4, independent walker ( 17 ). [academic.oup.com]

  • Respiratory Insufficiency

    Subtotal resection of this benign tissue mass ameliorated the respiratory insufficiency and led to sustained improvement in exercise tolerance, increase in pulmonary reserve, and decrease in signs of heart failure and pulmonary hypertension. [ncbi.nlm.nih.gov]

  • Osteoporosis

    Osteoporosis International. 2003, 14 (6): 507-514. 10.1007/s00198-003-1399-y. View Article PubMed Google Scholar Solomon DH, Rekedal L, Cadarette SM: Osteoporosis treatments and adverse events. [ijpeonline.biomedcentral.com]

    Calcium metabolism and 4 7 calcium kinetics before and after long-term thyrocalcitonin treatment in senile osteoporosis. Clin. Sci. 1970: 38, 397–407. Google Scholar 21. Ryan, W. G., Schwartz, T. B. [link.springer.com]

    Primary and secondary osteoporosis, symptomatic Paget disease of bone, osteogenesis imperfecta both in children and adults and fibrous dysplasia are currently the major indications for bisphospho-nates. [indianpediatrics.net]

    Osteoporosis may be caused by or worsened by hyperthyroidism. In some cases, hyperthyroidism cannot be controlled by medication. [rarediseases.org]

  • Back Pain

    This 25-year-old woman with polyostotic fibrous dysplasia (McCune-Albright syndrome) suffered low-back pain after a minor traumatic injury. Neurological examination demonstrated normal status. [ncbi.nlm.nih.gov]

    Case 2: A 20-year-old female was seen at another hospital for low back pain of two years duration and had X-rays of lumbosacral spine which were reported as metastatic malignancy. She was referred to this department. [ijcasereportsandimages.com]

    27740949 ) Hennessy G....Mansberg R. 2016 46 Two-Stage Surgical Treatment of Complex Femoral Deformities with Severe Coxa Vara in Polyostotic Fibrous Dysplasia. ( 30237924 ) Ippolito E...Fichera A 2016 47 Polyostotic fibrous dysplasia presenting with back [malacards.org]

  • Bowing of The Long Bones

    Bowing of the long bones occurs frequently in the polyostotic form, and stress fractures often result. Shepherd's crook deformity is a characteristic feature of fibrous dysplasia. [ncbi.nlm.nih.gov]

  • Coxa Valga

    RESULTS: Six reproducible patterns of deformity were identified in both untreated and operated femurs: type 1 (24%), normal neck-shaft angle with altered shape of the proximal femur; type 2 (6%), isolated coxa valga with neck-shaft angle 140 ; type 3 [ncbi.nlm.nih.gov]

  • Elbow Pain

    His main complaint was left elbow pain and a mass, which increased in size. The histological diagnosis from the needle biopsy was fibrous dysplasia. An articulated unilateral external fixator was used for immobilization. [ncbi.nlm.nih.gov]

  • Cafe-Au-Lait Spots

    When melanotic pigmentation (cafe-au-lait spots) and multiple endocrine hyperfunction are additionally associated it is referred to as albright syndrome ICD-9-CM Volume 2 Index entries containing back-references to 756.54 : [icd9data.com]

    McCune-Albright syndrome ( MAS ) is a genetic disorder characterized by the association of: endocrinopathy: precocious puberty polyostotic fibrous dysplasia: more severe than in sporadic cases cutaneous pigmentation: coast of Maine ' cafe au lait ' spots [radiopaedia.org]

    Other symptoms include: Bone fractures Deformities of the bones in the face Gigantism Irregular, large patchy cafe-au-lait spots There is no specific treatment for McCune-Albright syndrome. [medlineplus.gov]

    It is characterized by a typical phenotype which includes polyostotic fibrodysplasia, precocious puberty independent from gonadotropins, cafe-au-lait spots and a series of endocrine abnormalities. [bone-abstracts.org]

    When melanotic pigmentation (cafe-au-lait spots) and multiple endocrine hyperfunction are additionally associated it is referred to as albright syndrome. [icd10data.com]

  • Hyperpigmentation

    It is characterized by deformities and fractures of the bones, endocrine abnormalities including early puberty, and skin hyperpigmentation Fibrous dysplasia of bone affecting several bones. [icd9data.com]

    INTRODUCTION: Fibrous dysplasia (FD) is a disorder involving either one (monostotic) or several bones (polyostotic FD [PFD] and sometimes is associated with cafe- au -lait hyperpigmentation of the skin and one or more hyperfunctioning endocrinopathies [ncbi.nlm.nih.gov]

    THE McCUNE ALBRIGHT SYNDROME: THE McCUNE ALBRIGHT SYNDROME POLYOSTOTIC FIBROUS DYSPLASIA CUTANEOUS HYPERPIGMENTATION ENDOCRINE HYPERFUNCTION The Classic TRIAD ... [slideee.com]

    It is characterized by deformities and fractures of the bones, endocrine abnormalities including early puberty, and skin hyperpigmentation. Fibrous dysplasia of bone affecting several bones. [icd10data.com]

    Introduction McCune-Albright Syndrome (MAS) is a rare disease presenting with the classical triad of polyostotic fibrous dysplasia (FD), skin hyperpigmentation (café-au-lait spots) and endocrine dysfunction, usually seen as precocious puberty in females [ijpeonline.biomedcentral.com]

  • Facial Pain

    Significant correlations were not found for headache/facial pain or recurrent/chronic sinusitis. Thirty-one subjects met the criteria for longitudinal analysis (follow-up mean, 6.3 years; range, 4.4-9 years). [ncbi.nlm.nih.gov]

    […] contain spicules of woven bone with typical osteoblasts embedded within fibrous component.[ 5 ] Clinically FD result to pain, deformity, fracture, and nerve entrapments,[ 4 ] but it usually depends on which bone is involved and consist of: Propetosis, facial [surgicalneurologyint.com]

  • Myelopathy

    In the spine, PFD may lead to pathologic fracture and myelopathy even after adolescence. Vertebroplasty with or without decompression and fixation may be the appropriate option for cases with myelopathy. [ncbi.nlm.nih.gov]

    Considering the advanced radiographic findings in multiple vertebrae and possibility of impending paraplegia, the patient was referred to UK for confirmation of the diagnosis and for prophylactic surgical fusion, to prevent compressive myelopathy. [ijcasereportsandimages.com]

    Wu FL, et al: Polyostotic fibrous dysplasia involving the thoracic spine with myelopathy: case report and review of the literature. Spine J 2014;14:e11-e15. [karger.com]

  • Radiculopathy

    A 35-year-old man with McCune-Albright syndrome and severe polyostotic fibrous dysplasia of C2 and C3 vertebrae presented with severe neck pain, radiculopathy, quadriparesis and myelopathy. [ncbi.nlm.nih.gov]

The cornerstones of diagnosis in PFD are imaging, and if needed, histological evaluation.

The first line in the workup is a plain radiograph. The diagnosis is straightforward in the presence of typical findings. Computed tomography (CT) scans are necessary to assess complex parts of the skeleton like the pelvis, spine, chest, and facial bones [7] [8] [9] [10].

Bone scintigraphy is of limited use in detecting subtle pathologic fractures. The features of a bone scan in fibrous dysplasia are non-specific. Magnetic resonance imaging (MRI) is required for the assessment of cord compression if the spine is involved [11] [12] [13].

On plain radiography, fibrous dysplasia is observed as a well-defined, intramedullary and expansile lesion in the metaphysis or diaphysis. Lesions can range from completely radiolucent to sclerotic, although, most lesions have the characteristic ground-glass appearance [6]. The underlying histopathology of the lesion correlates directly with the amount of haziness shown radiographically. Radiolucent parts are mainly composed of fibrous elements whereas radiopaque lesions have a larger proportion of woven bone.

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. [ncbi.nlm.nih.gov]

These data have implications for long-term prognosis, clinical management, and interpretation of therapeutic interventions. [ncbi.nlm.nih.gov]

PROGNOSIS Biological Behavior • Benign tumor • Monostotic lesions have good prognosis • Polyostotic lesions tend to be more active or aggresive • Recurrence following curettage is common particularly when bone grafting the defect with autologous bone [tumorsurgery.org]

Thus, the prognosis varies according to the manifestations of MAS. With precocious puberty, the prognosis depends on the duration of premature estrogen exposure. [emedicine.medscape.com]

- progression of the disease is often erratic; - monostotic lesions : have good prognosis; - polyostotic lesions: - tend to remain more active or aggressive; - are known to occassionally undergo malignant transformation to osteosarcoma or fibrosarcoma [wheelessonline.com]

Bone is woven rather than lamellar and lacks osteoblastic rimming of trabeculae Treatment Monostotic : curettage and grafting, if symptomatic Polyostotic : symptomatic treatment May require osteotomy for deformity or lengthening / shortening procedures Prognosis [orthopaedicsone.com]

[…] involve in 10% of the monostotic cases and 50–100% of polyostotic cases.[ 1 ] In the skull, FD can involve any bone but the most common site is the frontal bone followed by sphenoid, parietal, ethmoid, temporal, and occipital bones.[ 1 ] The genetic etiology [surgicalneurologyint.com]

Expanded sections on etiology, treatment, and diagnosis of oral cancer (HPV) describe how subtypes can play an important role in the development and natural history of some head and neck cancers, most notably those arising in the oropharynx. [books.google.com]

Etiology unknown Most common 3-15 years Fundamental abnormality is replacement of medullary bone by fibrous tissue Clinically Deformities Shepherd’s crook deformity of femur Bone pain Most commonly involved bones are pelvis, femora In widespread disease [learningradiology.com]

INTRODUCTION Mc Cune-Albright syndrome is a disease of unknown etiology consisting of polyostotic fibrous dysplasia of bone assoCiate.d with brown pigmented areas of the skin and several endocrine dysfunctions (1,2). [docslide.com.br]

[…] molecular etiology of MAS [ 25, 26 ] (Fig. 5 ). [ojrd.biomedcentral.com]

Updated Molecular and Epidemiologic diagrams added to all new chapters. [books.google.com]

All cells descended from the mutated cell can manifest features of McCune-Albright syndrome. [ 3 ] Epidemiology McCune-Albright syndrome is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. [ 1 ] Gonadotrophin-independent precocious [patient.info]

Metyrapone may also be used for treatment. [12] Epidemiology [ edit ] McCune–Albright syndrome is estimated to occur at a frequency between 1 person in 100,000 to 1 person in 1,000,000 individuals worldwide. [15] Notable cases [ edit ] Mauricio Saravia [en.wikipedia.org]

Epidemiology United States and international statistics The exact incidence of MAS in the United States and internationally is unknown, but its prevalence is probably between 1 case in 100,000 population and 1 case in 1 million population, rendering it [emedicine.medscape.com]

Epidemiology This disorder is usually diagnosed in childhood or early adulthood. Usual presentation is in children and adolescents, with a median onset age of 8 years. Fibrous dysplasia makes about 5% of all benign bone tumors. [boneandspine.com]

Pathophysiology, evaluation, and treatment. J Bone Joint Surg Am. 2005;87:1848-1864. Lietman SA, Ding C, Levine MA. [rarediseases.org]

Fibrous dysplasia pathophysiology, evaluation, and treatment. J Bone Joint Surg Am. 2005; 87:1848–1864. doi:10.2106/JBJS.D.02942 [CrossRef] Feller L, Wood N, Khammissa R, et al. The nature of fibrous dysplasia. [healio.com]

"The Role of Type 1 and Type 2 5′-Deiodinase in the Pathophysiology of the 3,5,3′-Triiodothyronine Toxicosis of McCune-Albright Syndrome". The Journal of Clinical Endocrinology and Metabolism. 93 (6): 2383–2389. doi : 10.1210/jc.2007-2237. [en.wikipedia.org]

The role of type 1 and type 2 5'-deiodinase in the pathophysiology of the 3,5,3'-triiodothyronine toxicosis of McCune-Albright syndrome. J Clin Endocrinol Metab. 2008 Jun. 93(6):2383-9. [Medline]. [Full Text]. Lietman SA, Ding C, Levine MA. [emedicine.medscape.com]

Pathophysiology Fibrous dysplasia is caused by the sporadic mutation of the GNAS1 gene. As a consequence of the mutation, there is a substitution of cysteine or histidine in amino acids of the osteoblastic cells, by arginine. [boneandspine.com]

INTERPRETATION: In polyostotic fibrous dysplasia, multiple osteotomies and intramedullary nailing with neck cross-pinning can be used to correct developed or progressing shepherd's crook deformity, and to prevent recurrence and refracture. [ncbi.nlm.nih.gov]

Bisphosphonates are helpful in relieving bone pain, but it is no longer believed that they prevent progression of the disease. [en.wikipedia.org]

But now, in hopes that her story might call attention to the need for increased resources for the study, treatment and prevention of rare diseases – and community support for children and families suffering from them – Gorbach has decided it’s time to [globalgenes.org]

Expanded section on bisphosphonate-related osteonecrosis of the jaws helps you effectively manage patients taking bisphosphonates to prevent bone loss, including information on oral complications, risk factors, and benefits. [books.google.com]

This mutation, often a mosaicism, prevents downregulation of cAMP signalling. [wikidoc.org]

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  2. Leet AI, Wientroub S, Kushner H, et al. The correlation of specific orthopaedic features of polyostotic fibrous dysplasia with functional outcome scores in children. J Bone Joint Surg Am. 2006;88(4):818-23.
  3. Albright F, Butler AM, Hampton AO, Smith PH. Syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction, with precocious puberty in females, report of five cases. N Engl J Med. 1937;216:727-46.
  4. McCune DJ. Osteitis fibrosa cystica; the case of a nine year old girl who also exhibits precocious puberty, multiple pigmentation of the skin and hyperthyroidism. Am J Dis Child. 1936;52:743-4.
  5. Shah ZK, Peh WC, Koh WL, Shek TW. Magnetic resonance imaging appearances of fibrous dysplasia. Br J Radiol. 2005;78(936):1104-15.
  6. Parekh SG, Donthineni-Rao R, Ricchetti E, Lackman RD. Fibrous dysplasia. J Am Acad Orthop Surg. 2004;12(5):305-13.
  7. Bulakbasi N, Bozlar U, Karademir I, Kocaoglu M, Somuncu I. CT and MRI in the evaluation of craniospinal involvement with polyostotic fibrous dysplasia in McCune-Albright syndrome. Diagn Interv Radiol. 2008;14(4):177-81.
  8. Unal Erzurumlu Z, Celenk P, Bulut E, Barıs YS. CT Imaging of Craniofacial Fibrous Dysplasia. Case Rep Dent. 2015;134123.
  9. Atalar MH, Salk I, Savas R, Uysal IO, Egilmez H. CT and MR Imaging in a Large Series of Patients with Craniofacial Fibrous Dysplasia. Pol J Radiol. 2015;80:232-40.
  10. An G, Gui L, Liu J, Niu F, Chen Y, Wang M. Treatment of fibrous dysplasia orbital deformities with digital imaging guidance. J Craniofac Surg. 2015;26(2):449-51.
  11. Sood A, Raman R, Jhobta A, Dhiman DS, Seam RK. Normal technetium-99m-MDP uptake in fibrous dysplasia of the hip. Hell J Nucl Med. 2009 Jan-Apr; 12(1):72-3.
  12. Bonekamp D, Jacene H, Bartelt D, Aygun N. Conversion of FDG-PET activity of fibrous dysplasia of the skull late in life mimicking metastatic disease. Clin Nucl Med. 2008;33(12):909-11.
  13. Qu N, Yao W, Cui X, Zhang H. Malignant transformation in monostotic fibrous dysplasia: clinical features, imaging features, outcomes in 10 patients, and review. Medicine (Baltimore). 2015;94(3):e369.