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NORD (National Organization for Rare Disorders)

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REVIEW ARTICLES
Pignolo RJ and Kaplan FS. Druggable targets, clinical trial design and proposed pharmacological management in fibrodysplasia ossificans progressiva.Expert Opinion on Orphan Drugs 2020; 8:4, 101-109, DOI: 10.1080/21678707.2020.1751122

Zimmer C. The mystery of the second skeleton. Atlantic Monthly. 2013;311(5): 72-82.

Shore EM, Kaplan FS. Role of altered signal transduction in heterotopic ossification and fibrodysplasia ossificans progressiva. Curr Osteoporosis Rep. 2011;9: 83-88.

Shore EM, Kaplan FS. Inherited human diseases of heterotopic bone formation. Nat Rev Rheumatol. 2010;6: 518-527.

JOURNAL ARTICLES
Towler OW, Shore EM, Kaplan FS. Skeletal malformations and developmental arthropathy in individuals who have fibrodysplasia ossificans progressiva. Bone 2020 Jan;130:115116. doi: 10.1016/j.bone.2019.115116. Epub 2019 Oct 23.

Pignolo R.J., Baujat G, Brown MA, DeCunto C, DiRocco M, Hsiao EC, Keen R, Al Mukaddam M, LeQuan Sang K-H, Wilson A, White B, Grogan DR, Kaplan FS. Natural history of fibrodysplasia ossificans progressiva: cross-sectional analysis of annotated baseline phenotypes. Orphanet J. Rare Diseases 2019; 14: 98. https://doi.org/10.1186/s13023-019-1068-7

Hsaio EC, DiRocco M, Cali A. Zasloff M, Al Mukaddam M, Pignolo R, Grunwald Z, Netelenbos C, Keen R, Baujat G, Brown MA, Cho T-J De Cunto C, Delai P, Haga N, Morhart R, Scott C, Zhang K, Diecidue RJ, Friedman CS, Kaplan FS, Eekhoff EMW. Special considerations for clinical trials in fibrodysplasia ossificans progressiva. Br J Clin Pharmacol [Epub ahead of print], 2018.

Kaplan FS, Al Mukaddam M, Pignolo RJ. Longitudinal patient-reported mobility assessment in fibrodysplasia ossificans progressiva (FOP). Bone 2018;109:150-161.

Pignolo RJ, Durbin-Johnson BP, Rocke DM, Kaplan FS. Joint -specific risk of impaired function in fibrodysplasia ossificans progressiva (FOP). Bone 2018; 109:124-133.

Convente MR, Chakkalakal SA, Yang E, Caron RJ, Zhang D, Kambayashi T, Kaplan FS, Shore EM. Depletion of Mast cells and macrophages impairs heterotopic ossification in an ACVR1 (R206H) mouse model of fibrodysplasia ossificans progressiva. J Bone Miner Res. 2018; 33: 269-282.

Wang H, Shore EM, Pignolo RJ, Kaplan FS. Activin A amplifies dysregulated BMP signaling and induced chondro-osseous differentiation of primary connective tissue progenitor cells in patients with fibrodysplasia ossificans progressiva (FOP). Bone 2018;109: 218-224.

Gupta RR, Delai PLR, Glaser DL, Rocke DM, Al Mukaddam M, Pignolo RJ, Kaplan FS. Prevalence and risk factors for kidney stones in fibrodysplasia ossificans progressiva. Bone 2018;109: 120-123.

Lees-Shepard JB, Yamamoto M, Biswas AA, Stoessel SJ, Nicholas SE, Cogswell CA, Devarakonda PM, Schneider MJ Jr, Cummins SM, Legendre NP, Yamamoto S, Kaartinen V, Hunter JW, Goldhamer DJ. Activin-dependent signaling in fibro/adipogenic progenitors causes fibrodysplasia ossificans progressiva. Nat Commun. 2018 Feb 2;9(1):471. doi: 10.1038/s41467-018-02872-2.

Pignolo RJ , Bedford-Gay C Liljesthröm M Durbin-Johnson BP , Shore EM , Rocke DM , Kaplan FS. The natural history of flare-ups in fibrodysplasia ossificans progressiva (FOP): a comprehensive global assessment. J Bone Miner Res. 2016 Mar;31(3):650-6.

Wang H, Lindborg C, Lounev V, Kim J, McCarrick-Walmsley R, Xu M, Mangiavini L, Groppe J, Shore E, Schipani E, Kaplan F, Pignolo R. Cellular Hypoxia Promotes Heterotopic Ossification by Amplifying BMP Signaling. J Bone Miner Res. 2016 Sep;31(9):1652-65.

Hatsell SJ, Idone V, Wolken DM, Huang L, Kim HJ, Wang L, Wen X, Nannuru KC, Jimenez J, Xie L, Das N, Makhoul G, Chernomorsky R, D'Ambrosio D, Corpina RA, Schoenherr CJ, Feeley K, Yu PB, Yancopoulos GD, Murphy AJ, Economides AN. ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A. Sci Transl Med. 2015;Sep 2;7(303):303ra137.

Hino K, Ikeya M, Horigome K, Matsumoto Y, Ebise H, Nishio M, Sekiguchi K, Shibata M, Nagata S, Matsuda S, Toguchida J. Neofunction of ACVR1 in fibrodysplasia ossificans progressiva. PNAS 2015; doi/10.1073/pnas.1510540112.

Chakkalakal SA, Zhang D, Culbert AL, Convente MR, Caron RJ, Wright AC, Maidment AD, Kaplan FS, Shore EM. An Acvr1 Knock-in mouse has fibrodysplasia ossificans progressiva. J Bone Miner Res. 2012; 27:1746-1756.

Kaplan FS, Zasloff MA, Kitterman JA, Shore EM, Hong CC, Rocke DM. Early mortality and cardiorespiratory failure in patients with fibrodysplasia ossificans progressiva. J Bone Joint Surg Am. 2010;92:686-691.

Kaplan FS, Xu M, Seemann P, Connor JM, Glaser DL, Carroll L, Delai, P, Xu M, Seemann P, Fastnacht-Urban E, Forman SJ, Gillessen-Kaesbach G, Hoover-Fong J, Köster B, Pauli RM, Reardon W, Zaidi S-A, Zasloff M, Morhart R, Mundlos S, Groppe J, and Shore EM. Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat. 2009;30(3):379-390.

Shen Q, Little SC, Xu M, Haupt J, Ast C, Katagiri T, Mundlos S, Seemann P. Kaplan FS, Mullins MC, Shore EM. The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization. J Clin Invest. 2009;119(11):3462-3472.

Deirmengian GK, Hebela NM, O'Connell M, Glaser DL, Shore EM, Kaplan FS. Proximal tibial osteochondromas in patients with fibrodysplasia ossificans progressiva. J Bone Joint Surg Am. 2008;90:366-374.

Adegbite NS, Xu M, Kaplan FS, Shore EM, Pignolo RJ. Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS-based heterotopic ossification. Am J Med Genet A. 2008;146A:1788-1796.

Kaplan FS, Xu M, Glaser DL Collins F, Connor M, Kitterman J, Sillence D, Zackai E, Ravitsky V, Zasloff M, Ganguly A, Shore EM. Early diagnosis of fibrodysplasia ossificans progressiva. Pediatrics. 2008;121:e1295-e1300.

Kaplan FS, Glaser DL, Shore EM, Pignolo RJ, Xu M, Zhang Y, Senitzer D, Forman SJ, Emwerson SG. Hematopoietic stem cell contribution to ectopic skeletogenesis. J Bone Joint Surg Am. 2007;89:347-357.

Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho T-J, Choi IH, Connor JM, Delai P, Glaser DL, Le Merrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nature Genetics. 2006;38:525-527.

Kitterman JA, Kantanie S, Rocke DM, Kaplan FS. Iatrogenic harm caused by diagnostic errors in fibrodysplasia ossificans progressiva. Pediatrics. 2005;116:e654-61.

INTERNET
Kaplan FS, Al Mukaddam M, Baujat G, Brown M, Cali A, Cho T-J, Crowe C, DeCunto C, Delai P, Diecidue, R, Di Rocco M, Eekhoff EMW, Friedman C, Grunwald Z, Haga N. Hsiao E, Keen R, Kitterman J, Levy C, Morhart R, Netelenbos C, Scott C, Shore EM, Zasloff M, Zhang K, Pignolo RJ. The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Proc Intl. Clin. Council FOP 2019; 1:1-111. https://www.ifopa.org/international_clinical_council_on_fop Accessed May 20, 2020.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Fibrodysplasia Ossificans Progressiva; FOP. Entry No:135100. Last Updated 09/19/2017. Available at: http://omim.org/entry/135100 Accessed May 20, 2020.

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Fibrodysplasia Ossificans Progressiva - NORD (National Organization for Rare Disorders)

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REVIEW ARTICLES Pignolo RJ and Kaplan FS. Druggable targets, clinical trial design and proposed pharmacological management in fibrodysplasia ossificans progressiva.Expert Opinion on Orphan Drugs 2020; 8:4, 101-109, DOI: 10.1080/21678707.2020.1751122 Zimmer C. The mystery of the second skeleton. Atlantic Monthly. 2013;311(5): 72-82. Shore EM, Kaplan FS.

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Fibrodysplasia ossificans progressiva | Genetic and Rare Diseases Information Center (GARD) - an NCATS Program

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A collection of disease information resources and questions answered by our Genetic and Rare Diseases Information Specialists for Fibrodysplasia ossificans progressiva

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Enjoy the videos and music you love, upload original content, and share it all with friends, family, and the world on YouTube.

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Fibrodysplasia ossificans progressiva (FOP) is a disorder in which skeletal muscle and connective tissue, such as tendons and ligaments, are gradually replaced by bone. This condition leads to bone formation outside the skeleton that restricts movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and moving down the body and into the limbs. People with FOP are born with abnormal big toes which can be helpful in making the diagnosis. Trauma, such as a fall or invasive medical procedure, or a viral illness may trigger episodes of muscle swelling and inflammation. FOP is almost always caused by a mutation at the same place in the ACVR1 gene. This condition occurs in about 1 in 1,600,000 newborns and about 800 people worldwide are known to have FOP.

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Danielle Coyne is a BYU graduate that was diagnosed with FOP at the age of five and is now a public service worker

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1. Big toes
2. Pain in joints
3. Loss of movement
4. Hard bumps from hitting an object

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Extra-skeletal bone formation causes progressive loss of mobility as the joints become affected. Inability to fully open the mouth may cause difficulty in speaking and eating. Over time, people with this disorder may experience malnutrition due to their eating problems. They may also have breathing difficulties as a result of extra bone formation around the rib cage that restricts expansion of the lungs.