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    607 results match your criteria Fibrodysplasia Ossificans

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    Longitudinal study of the activities of daily living and quality of life in Japanese patients with fibrodysplasia ossificans progressiva.
    Disabil Rehabil 2017 Nov 16:1-6. Epub 2017 Nov 16.
    a Department of Rehabilitation Medicine, Graduate School of Medicine , The University of Tokyo , Tokyo , Japan.
    Purpose: Fibrodysplasia ossificans progressiva is a rare congenital disorder that causes systemic heterotopic ossification, leading to systemic ankyloses and mobility losses. This study aimed to ascertain the natural history of fibrodysplasia ossificans progressiva.

    Methods: In addition to the medical history questionnaire, patients aged 16 years and older were asked to complete activities of daily living and quality of life surveys using the Barthel Index, MOS 36-Item Short-Form Health Survey, and Health Assessment Questionnaire. Read More

    Correction to: Rarely occurring mutation of ACVR1 gene in Moroccan patient with fibrodysplasia ossificans progressiva.
    Clin Rheumatol 2017 Nov 13. Epub 2017 Nov 13.
    Department of Medical Genetics, National Institute of Health, 27 Avenue Ibn Batouta, BP 769, 11400, Rabat, Morocco.
    One of the author's name on this article was incorrectly spelled as "Renata Borcciadi". The correct spelling is "Renata Bocciardi" and is now presented correctly in this article. Read More

    Drosophila models of FOP provide mechanistic insight.
    Bone 2017 Nov 8. Epub 2017 Nov 8.
    Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA. Electronic address:
    Fibrodysplasia ossificans progressiva (FOP) is a rare bone disease characterized by episodic events of heterotopic ossification (HO). All cases of FOP have been attributed to mutations in the ACVR1 gene that render the encoded BMP type I ALK2 receptor hypersensitive, resulting in the activation of BMP signaling, at inappropriate times in inappropriate locations. The episodic or sporadic nature of HO associated with FOP rests with the occurrence of specific 'triggers' that push the hypersensitive ALK2-FOP receptor into full signaling mode. Read More

    Palovarotene inhibits osteochondroma formation in a mouse model of multiple hereditary exostoses.
    J Bone Miner Res 2017 Nov 9. Epub 2017 Nov 9.
    Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
    Multiple hereditary exostoses (MHE), also known as multiple osteochondromas (MO), is an autosomal dominant disorder characterized by the development of multiple cartilage-capped bone tumors (osteochondromas). The large majority of patients with MHE carry loss-of-function mutations in the EXT1 or EXT2 gene, which encodes a glycosyltransferase essential for heparan sulfate (HS) biosynthesis. Increasing evidence suggests that enhanced BMP signaling resulting from loss of HS expression plays a role in osteochondroma formation in MHE. Read More

    Hints on transcriptional control of essential players in heterotopic ossification of Fibrodysplasia Ossificans Progressiva.
    Bone 2017 Oct 31. Epub 2017 Oct 31.
    DINOGMI Department, University of Genova, Genova, Italy; Medical Genetics Unit, Istituto Giannina Gaslini, Genova, Italy.
    Signaling of the Bone Morphogenetic Protein (BMP) pathway is influenced by the level of expression of its components, in particular receptors, intracellular molecules and target genes which largely depends on gene transcription. One peculiar aspect of Fibrodysplasia Ossificans Progressiva (FOP) relates to the cell types in which the genetic mutation exerts its effects, then not only those involved in the heterotopic ossification processes but also others that participate in the inflammatory phases preceding and triggering heterotopic ossification. Such effects are in part detectable as variation in gene expression, which is also variably manifesting in term of time of appearance in different phases of the inflammatory or ossification processes. Read More

    Variable signaling activity by FOP ACVR1 mutations.
    Bone 2017 Oct 31. Epub 2017 Oct 31.
    Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:
    Most patients with fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder of heterotopic ossification, have the same causative mutation in ACVR1, R206H. However, additional mutations within the ACVR1 BMP type I receptor have been identified in a small number of FOP cases, often in patients with disease of lesser or greater severity than occurs with R206H mutations. Genotype-phenotype correlations have been suggested in patients, resulting in classification of FOP mutations based on location within different receptor domains and structural modeling. Read More

    Clinical-pathological correlations in three patients with fibrodysplasia ossificans progressiva.
    Bone 2017 Oct 13. Epub 2017 Oct 13.
    Division of Endocrinology, Diabetes, and Metabolism, Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States. Electronic address:
    Objective: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder in which heterotopic bone forms in the soft tissues. This often occurs in response to injury or inflammation, leading to joint immobilization and significant disability. There are currently no definitive treatment options for this devastating disease. Read More

    Depletion of Mast Cells and Macrophages Impairs Heterotopic Ossification in an Acvr1(R206H) Mouse Model of Fibrodysplasia Ossificans Progressiva.
    J Bone Miner Res 2017 Oct 7. Epub 2017 Oct 7.
    Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
    Heterotopic ossification (HO) is a clinical condition that often reduces mobility and diminishes quality of life for affected individuals. The most severe form of progressive HO occurs in those with fibrodysplasia ossificans progressiva (FOP; OMIM #135100), a genetic disorder caused by a recurrent heterozygous gain-of-function mutation (R206H) in the bone morphogenetic protein (BMP) type I receptor ACVR1/ALK2. In individuals with FOP, episodes of HO frequently follow injury. Read More

    Peripheral blood mononuclear cell immunophenotyping in fibrodysplasia ossificans progressiva patients: Evidence for monocyte DNAM1 up-regulation.
    Cytometry B Clin Cytom 2017 Oct 6. Epub 2017 Oct 6.
    IRCCS Istituto Giannina Gaslini, Genova, Italy.
    Background: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder caused by sporadic heterozygous mutations in ACVR1 gene which progressively leads to severe heterotopic ossification. FOP is characterized by episodic flare-ups triggered by different factors such as viral infections, tissue injuries, vaccinations, or occurring without a recognizable cause. The sporadic course of the disease, the documented presence of an important inflammatory reaction in early lesions and the partial response to corticosteroids support the idea that the immune system, and in particular the innate component, may play a role in FOP pathogenesis. Read More

    Cartilage-derived retinoic acid-sensitive protein (CD-RAP): A stage-specific biomarker of heterotopic endochondral ossification (HEO) in fibrodysplasia ossificans progressiva (FOP).
    Bone 2017 Sep 28. Epub 2017 Sep 28.
    Department of Medicine, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, United States. Electronic address:
    Background: Genesis of a cartilaginous scaffold is an obligate precursor to bone formation in heterotopic endochondral ossification (HEO). We tested the hypothesis that cartilage-derived retinoic acid-sensitive protein (CD-RAP) can serve as a plasma biomarker for the pre-osseous cartilaginous stage of HEO. Palovarotene, a retinoic acid receptor-gamma (RARγ) agonist, has been proposed as a possible treatment for fibrodysplasia ossificans progressiva (FOP) and is a potent inhibitor of HEO in mouse models. Read More

    Clinical staging of Fibrodysplasia Ossificans Progressiva (FOP).
    Bone 2017 Sep 21. Epub 2017 Sep 21.
    Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address:
    Fibrodyplasia ossificans progressiva (FOP) is an ultra-rare genetic condition of heterotopic ossification (HO) that results in progressive loss of joint function, ultimately rendering movement impossible. Death is most commonly the result of thoracic insufficiency syndrome, or complications related to recurrent respiratory infections. There are no current treatments for FOP, but early and emerging clinical trials offer hope for this devastating disease. Read More

    Structural basis for the potent and selective binding of LDN-212854 to the BMP receptor kinase ALK2.
    Bone 2017 Sep 12. Epub 2017 Sep 12.
    Structural Genomics Consortium, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ, UK. Electronic address:
    Individuals with the rare developmental disorder fibrodysplasia ossificans progressiva (FOP) experience disabling heterotopic ossification caused by a gain of function mutation in the intracellular region of the BMP type I receptor kinase ALK2, encoded by the gene ACVR1. Small molecule BMP type I receptor inhibitors that block this ossification in FOP mouse models have been derived from the pyrazolo[1,5-a]pyrimidine scaffold of dorsomorphin. While the first derivative LDN-193189 exhibited pan inhibition of BMP receptors, the more recent compound LDN-212854 has shown increased selectivity for ALK2. Read More

    The FOP Connection Registry: Design of an international patient-sponsored registry for Fibrodysplasia Ossificans Progressiva.
    Bone 2017 Sep 1. Epub 2017 Sep 1.
    International FOP Association, 1520 Clay St, Suite H2, North Kansas City, MO 64116, USA. Electronic address:
    The Fibrodysplasia Ossificans Progressiva (FOP) Connection Registry is an international, voluntary, observational study that directly captures demographic and disease information initially from patients with FOP (the patient portal) and in the near future from treating physicians (the physician portal) via a secure web-based tool. It was launched by the International FOP Association (IFOPA) with a guiding vision to develop and manage one unified, global, and coordinated Registry allowing the assembly of the most comprehensive data on FOP. This will ultimately facilitate greater access and sharing of patient data and enable better and faster development of therapies and tracking their long-term treatment effectiveness and safety. Read More

    Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway.
    J Neurosci 2017 Aug 3;37(35):8524-8533. Epub 2017 Aug 3.
    Department of Biology, College of Arts and Sciences, University of New England, Biddeford, Maine 04005,
    Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Read More

    Mast cell inhibition as a therapeutic approach in fibrodysplasia ossificans progressiva (FOP).
    Bone 2017 Aug 26. Epub 2017 Aug 26.
    Department of Medicine, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, United States. Electronic address:
    Background: Episodic flare-ups of fibrodysplasia ossificans progressiva (FOP) are characterized clinically by severe, often posttraumatic, connective tissue swelling and intramuscular edema, followed histologically by an intense and highly angiogenic fibroproliferative reaction. This early inflammatory and angiogenic fibroproliferative response is accompanied by the presence of abundant mast cells far in excess of other reported myopathies.

    Results: Using an injury-induced, constitutively-active transgenic mouse model of FOP we show that mast cell inhibition by cromolyn, but not aprepitant, results in a dramatic reduction of heterotopic ossification. Read More

    AMPK downregulates ALK2 via increasing the interaction between Smurf1 and Smad6, leading to inhibition of osteogenic differentiation.
    Biochim Biophys Acta 2017 Dec 25;1864(12):2369-2377. Epub 2017 Aug 25.
    Jiangxi Province Key Laboratory of Tumor Pathogenesis and Molecular Pathology, Department of Pathophysiology, Schools of Basic Sciences and Pharmaceutical Sciences, Nanchang University Medical College, Nanchang, China; Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, United States. Electronic address:
    Activin A receptor type I or activin receptor-like kinase 2 (ACVRI/ALK2) belongs to type I TGF-β family and plays an important role in bone development. Activating mutations of ALK2 containing the R206 to H mutation, are present in 95% in the rare autosomal genetic disease fibrodysplasia ossificans progressiva (FOP), which leads to the development of ectopic bone formation in muscle. The effect of AMP-activated protein kinase (AMPK) activation on ALK2R206H-mediated signaling in fibroblasts obtained from a FOP patient was assessed in the present study. Read More

    Natural development of dermal ectopic bone in the american alligator (Alligator mississippiensis) resembles heterotopic ossification disorders in humans.
    Anat Rec (Hoboken) 2017 Aug 24. Epub 2017 Aug 24.
    Department of Biological Sciences, University of North Texas, 1511 W. Sycamore St, Denton, Texas.
    Heterotopic ossification (HO) occurs when soft tissues are inappropriately converted to bony tissue. Several human diseases result in HO with few reliable treatment options. Animal models that naturally produce dermal ectopic bone (i. Read More

    Retinoid roles and action in skeletal development and growth provide the rationale for an ongoing heterotopic ossification prevention trial.
    Bone 2017 Aug 19. Epub 2017 Aug 19.
    Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States. Electronic address:
    The majority of skeletal elements develop via endochondral ossification. This process starts with formation of mesenchymal cell condensations at prescribed sites and times in the early embryo and is followed by chondrogenesis, growth plate cartilage maturation and hypertrophy, and replacement of cartilage with bone and marrow. This complex stepwise process is reactivated and recapitulated in physiologic conditions such as fracture repair, but can occur extraskeletally in pathologies including heterotopic ossification (HO), Ossification of the Posterior Longitudinal Ligament (OPLL) and Hereditary Multiple Exostoses (HME). Read More

    [18F]NaF PET/CT scan as an early marker of heterotopic ossification in fibrodysplasia ossificans progressiva.
    Bone 2017 Aug 18. Epub 2017 Aug 18.
    Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
    Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease with a progressive course characterized by episodically local flare-ups, which often but not always leads to heterotopic bone formation (HO). Recently, we showed that [18F]NaF PET/CT may be the first tool to monitor progression of a posttraumatic flare-up leading to new HO, which was demonstrated in a patient with FOP who underwent a maxillofacial surgery. This paper evaluates [18F]NaF PET/CT as a marker of FOP disease activity, comparing its use with other imaging modalities known in literature. Read More

    Imaging assessment of fibrodysplasia ossificans progressiva: Qualitative, quantitative and questionable.
    Bone 2017 Aug 16. Epub 2017 Aug 16.
    Department of Radiology, Division of Musculoskeletal Imaging and Intervention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States. Electronic address:
    Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare autosomal dominant genetic disorder of heterotopic ossification (HO) characterized by skeletal anomalies and episodic soft tissue swelling (flare-ups) that can transform into heterotopic bone. The progressive development of heterotopic bone and progressive arthropathy leads to significant limitation of mobility. This paper will review various imaging modalities used in evaluating episodic soft tissue swelling (flare-ups), heterotopic bone and skeletal anomalies. Read More

    Acute unilateral hip pain in fibrodysplasia ossificans progressiva (FOP).
    Bone 2017 Aug 16. Epub 2017 Aug 16.
    Department of Medicine, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, United States. Electronic address:
    Background: Flare-ups of the hips are among the most feared and disabling complications of fibrodysplasia ossificans progressiva (FOP) and are poorly understood. In order to better understand the nature of hip flare-ups in FOP, we evaluated 25 consecutive individuals with classic FOP (14 males, 11 females; 3-56years old, median age, 17years old) who presented with acute unilateral hip pain.

    Results: All 25 individuals were suspected of having a flare-up of the hip based on clinical history and a favorable response to a four day course of high-dose oral prednisone. Read More

    Unresolving trismus following third molar surgery: Report of a case of fibrodysplasia ossificans progressiva with review of literature.
    Cranio 2017 Aug 11:1-9. Epub 2017 Aug 11.
    a FDS, M.S.R.U.A.S., Gnanagangotri Campus , Bengaluru , India.
    Background: Trismus is a problem commonly encountered by the dental practitioner. It has a number of potential causes, and its treatment will depend on the cause. However, there are very few reports of trismus due to fibrodysplasia ossificans progressiva (FOP) following third molar surgery. Read More

    The Expansion of Heterotopic Bone in Fibrodysplasia Ossificans Progressiva Is Activin A-Dependent.
    J Bone Miner Res 2017 Aug 7. Epub 2017 Aug 7.
    Regeneron Pharmaceuticals, Tarrytown, NY, USA.
    Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder that is characterized by episodic yet cumulative heterotopic ossification (HO) in skeletal muscles, tendons, and ligaments over a patient's lifetime. FOP is caused by missense mutations in the type I bone morphogenetic protein (BMP) receptor ACVR1. We have determined that the formation of heterotopic bone in FOP requires activation of mutant ACVR1 by Activin A, in part by showing that prophylactic inhibition of Activin A blocks HO in a mouse model of FOP. Read More

    Shared ACVR1 mutations in FOP and DIPG: Opportunities and challenges in extending biological and clinical implications across rare diseases.
    Bone 2017 Aug 2. Epub 2017 Aug 2.
    Division of Neurosurgery, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Center for Data Driven Discovery in Biomedicine, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Colket Translational Research Building Room 4052, 3501 Civic Center Blvd, Philadelphia 19104, PA, United States; Department of Neurosurgery, Perelman School of Medicine at the University of Pennsylvania, 3501 Civic Center Blvd, Room 4052, Philadelphia 19104, PA, United States. Electronic address:
    Gain-of-function mutations in the Type I Bone Morphogenic Protein (BMP) receptor ACVR1 have been identified in two diseases: Fibrodysplasia Ossificans Progressiva (FOP), a rare autosomal dominant disorder characterized by genetically driven heterotopic ossification, and in 20-25% of Diffuse Intrinsic Pontine Gliomas (DIPGs), a pediatric brain tumor with no effective therapies and dismal median survival. While the ACVR1 mutation is causal for FOP, its role in DIPG tumor biology remains under active investigation. Here, we discuss cross-fertilization between the FOP and DIPG fields, focusing on the biological mechanisms and principles gleaned from FOP that can be applied to DIPG biology. Read More

    Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva.
    J Clin Invest 2017 Sep 31;127(9):3339-3352. Epub 2017 Jul 31.
    Department of Life Science Frontiers, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
    Fibrodysplasia ossificans progressiva (FOP) is a rare and intractable disease characterized by extraskeletal bone formation through endochondral ossification. Patients with FOP harbor point mutations in ACVR1, a type I receptor for BMPs. Although mutated ACVR1 (FOP-ACVR1) has been shown to render hyperactivity in BMP signaling, we and others have uncovered a mechanism by which FOP-ACVR1 mistransduces BMP signaling in response to Activin-A, a molecule that normally transduces TGF-β signaling. Read More

    Heterotopic bone induction via BMP signaling: Potential therapeutic targets for fibrodysplasia ossificans progressiva.
    Bone 2017 Jul 25. Epub 2017 Jul 25.
    Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
    More than 50years ago, Marshal M. Urist detected "heterotopic bone-inducing activity" in demineralized bone matrix. This unique activity was referred to as "bone morphogenetic protein (BMP)" because it was sensitive to trypsin digestion. Read More

    Atypical presentation and management of fibrodysplasia ossificans progressiva.
    BMJ Case Rep 2017 Jul 27;2017. Epub 2017 Jul 27.
    Centro Hospitalar de Lisboa Central EPE, Serviço de Ortopedia - Hospital de Curry Cabral, Lisboa, Portugal.
    We report a case of an 18-year-old woman, with bilateral acute inflammatory pain on the hip area, during the premenstrual period, and progressive increase in volume and rigidity of both hips. Bilateral exuberant soft tissue calcifications were present on the radiographic exams, and the patient also presented with bilateral short-length hallux valgus. A heterozygous mutation in the protein kinase domain of ACVR1 gene was found, allowing the diagnosis of fibrodysplasia ossificans progressive. Read More

    Early clinical observations on the use of imatinib mesylate in FOP: A report of seven cases.
    Bone 2017 Jul 20. Epub 2017 Jul 20.
    Department of Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, United States. Electronic address:
    Background: Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder of progressive, disabling heterotopic ossification (HO) for which there is presently no definitive treatment. Research studies have identified multiple potential targets for therapy in FOP, and novel drug candidates are being developed for testing in clinical trials. A complementary approach seeks to identify approved drugs that could be re-purposed for off-label use against defined targets in FOP. Read More

    [Characteristics of the joint involvement in fibrodysplasia ossificans progressiva and follow up].
    Zhonghua Er Ke Za Zhi 2017 Jul;55(7):519-522
    Division of Pediatric Rheumatology, Children's Hospital Capital Institute of Pediatrics, Beijing 100020, China.
    Objective: To summarize the clinical data of 15 patients with fibrodysplasia ossificans progressiva (FOP), follow up and analyze the characteristics of the joint involvement in FOP. Method: From May 2005 to December 2016, fifteen FOP cases had been diagnosed in the Children's Hospital Capital Institute of Pediatrics. All medical records and follow-up data were collected and a retrospective analysis was made on the joint involvement in FOP. Read More

    Strategic Targeting of Multiple BMP Receptors Prevents Trauma-Induced Heterotopic Ossification.
    Mol Ther 2017 Aug 15;25(8):1974-1987. Epub 2017 Jul 15.
    Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address:
    Trauma-induced heterotopic ossification (tHO) is a condition of pathologic wound healing, defined by the progressive formation of ectopic bone in soft tissue following severe burns or trauma. Because previous studies have shown that genetic variants of HO, such as fibrodysplasia ossificans progressiva (FOP), are caused by hyperactivating mutations of the type I bone morphogenetic protein receptor (T1-BMPR) ACVR1/ALK2, studies evaluating therapies for HO have been directed primarily toward drugs for this specific receptor. However, patients with tHO do not carry known T1-BMPR mutations. Read More

    Application of human induced pluripotent stem cells to model fibrodysplasia ossificans progressiva.
    Bone 2017 Jul 14. Epub 2017 Jul 14.
    Division of Endocrinology and Metabolism, Department of Medicine and the Institute for Human Genetics, University of California, San Francisco, CA 94143, United States. Electronic address:
    Fibrodysplasia ossificans progressiva (FOP) is a genetic condition characterized by massive heterotopic ossification. FOP patients have mutations in the Activin A type I receptor (ACVR1), a bone morphogenetic protein (BMP) receptor. FOP is a progressive and debilitating disease characterized by bone formation flares that often occur after trauma. Read More

    Periodontal ligament fibroblasts as a cell model to study osteogenesis and osteoclastogenesis in fibrodysplasia ossificans progressiva.
    Bone 2017 Jul 10. Epub 2017 Jul 10.
    Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
    Fibrodysplasia Ossificans Progressiva (FOP) is a progressive disease characterized by periods of heterotopic ossification of soft connective tissues, including ligaments. Though progress has been made in recent years in unraveling the underlying mechanism, patient-derived cell models are necessary to test potential treatment options. Periodontal ligament fibroblasts (PLF) from extracted teeth can be used to study deviant bone modeling processes in vitro since these cells are derived from genuine ligaments. Read More

    Prevalence of fibrodysplasia ossificans progressiva (FOP) in France: an estimate based on a record linkage of two national databases.
    Orphanet J Rare Dis 2017 Jun 30;12(1):123. Epub 2017 Jun 30.
    Institut Imagine, Centre de Référence Maladies Osseuses Constitutionnelles, Université Paris Descartes-Sorbonne Paris Cité, Hôpital Necker-Enfants malades, 149 rue de Sèvres, 75015, Paris, France.
    Background: Fibrodysplasia ossificans progressiva (FOP) is a rare, severely disabling, and life-shortening genetic disorder that causes the formation of heterotopic bone within soft connective tissue. Previous studies found that the FOP prevalence was about one in every two million lives. The aim of this study is to estimate the FOP prevalence in France by probabilistic record-linkage of 2 national databases: 1) the PMSI (Programme de médicalisation des systèmes d'information), an administrative database that records all hospitalization activities in France and 2) CEMARA, a registry database developed by the French Centres of Reference for Rare Diseases. Read More

    The obligatory role of Activin A in the formation of heterotopic bone in Fibrodysplasia Ossificans Progressiva.
    Bone 2017 Jun 16. Epub 2017 Jun 16.
    Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA; Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. Electronic address:
    Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disorder that presents at birth with only minor patterning defects, but manifests its debilitating pathology early in life with episodic, yet progressive and cumulative, heterotopic ossification (HO) of ligaments, tendons, and a subset of major skeletal muscles. The resulting HO lesions are endochondral in nature, and appear to be linked to inflammatory stimuli arising in association with known injuries, or from inflammation linked to normal tissue repair. FOP is caused by gain-of-function mutations in ACVR1, which encodes a type I BMP receptor. Read More

    Joint-specific risk of impaired function in fibrodysplasia ossificans progressiva (FOP).
    Bone 2017 Jun 13. Epub 2017 Jun 13.
    Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address:
    Background: Fibrodysplasia ossificans progressiva (FOP) causes progressive disability due to heterotopic ossification from episodic flare-ups. Using data from 500 FOP patients (representing 63% of all known patients world-wide), age- and joint-specific risks of new joint involvement were estimated using parametric and nonparametric statistical methods.

    Results: Compared to data from a 1994 survey of 44 individuals with FOP, our current estimates of age- and joint-specific risks of new joint involvement are more accurate (narrower confidence limits), based on a wider range of ages, and have less bias due to its greater comprehensiveness (captures over three-fifths of the known FOP patients worldwide). Read More

    International physician survey on management of FOP: a modified Delphi study.
    Orphanet J Rare Dis 2017 Jun 12;12(1):110. Epub 2017 Jun 12.
    Department of Orthopaedic Surgery, Center for Research in FOP & Related Disorders, The Perelman School of Medicine, The University of Pennsylvania, 3737 Market Street, Philadelphia, PA, 19104, USA.
    Fibrodysplasia ossificans progressiva (FOP), a disabling disorder of progressive heterotopic ossification (HEO), is caused by heterozygous gain-of- function mutations in Activin receptor A, type I (ACVR1, also known as ALK2), a bone morphogenetic protein (BMP) type I receptor. Presently, symptomatic management is possible, but no definitive treatments are available. Although extensive guidelines for symptomatic management are widely used, regional preferences exist. Read More

    Longitudinal patient-reported mobility assessment in fibrodysplasia ossificans progressiva (FOP).
    Bone 2017 Jun 6. Epub 2017 Jun 6.
    Department of Medicine, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, United States. Electronic address:
    Background: Fibrodysplasia ossificans progressiva (FOP) is a rare, disabling genetic disorder characterized by episodic soft tissue swelling (flare-ups) that leads to progressive heterotopic ossification and restricted joint mobility.

    Methods: Here we present the first longitudinal patient-reported mobility assessment (PRMA) in FOP based on a simple evaluation tool. At initial presentation and follow-up (1-11year span; median: 6 year span), 64 patients (36 females; 28 males) with classic FOP completed a questionnaire designed to rapidly assess mobility at 15 sites (three axial; six upper limb, and six lower limb). Read More

    Fibrodysplasia ossificans progressiva: a case report.
    Ghana Med J 2016 Dec;50(4):248-250
    Department of Surgery, Cape Coast Teaching Hospital, Cape Coast, Ghana.
    Fibrodysplasia Ossificans Progressiva is a rare debilitating disorder of the musculoskeletal system affecting one in two million individuals. It is characterized by progressive extraskeletal ossification of soft tissues resulting in the original skeleton being encased in unyielding new bone leading to disability and ultimately death from cardiorespiratory failure. The present case brings to light the delays and potential pitfalls in diagnosis as a result of the rarity of the condition. Read More

    Fibrodysplasia ossificans progressiva: The patient voice.
    Bone 2017 May 23. Epub 2017 May 23.
    The following essays are the personal statements of two remarkable young individuals, Ian Cali and Laura Rossano, who candidly share their perspectives on living life with fibrodysplasia ossificans progressiva (FOP). These essays are excerpts from the opening comments that Ian and Laura delivered at The First and The Second International FOP Association Drug Development Forums in 2014 and 2016, respectively. We present these unedited essays in this special issue of BONE so that physicians, scientists, and researchers everywhere can glimpse the valiant challenges that envelop the lives of all individuals with FOP and can appreciate that diseases are not just biological processes but indelible human experiences. Read More

    Evaluation of Salivary Cytokines for Diagnosis of both Trauma-Induced and Genetic Heterotopic Ossification.
    Front Endocrinol (Lausanne) 2017 24;8:74. Epub 2017 Apr 24.
    Burn/Wound and Regenerative Medicine Laboratory, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
    Purpose: Heterotopic ossification (HO) occurs in the setting of persistent systemic inflammation. The identification of reliable biomarkers can serve as an early diagnostic tool for HO, especially given the current lack of effective treatment strategies. Although serum biomarkers have great utility, they can be inappropriate or ineffective in traumatic acute injuries and in patients with fibrodysplasia ossificans progressiva (FOP). Read More

    The congenital great toe malformation of fibrodysplasia ossificans progressiva? - A close call.
    Eur J Med Genet 2017 Jul 1;60(7):399-402. Epub 2017 May 1.
    Department of Orthopaedic Surgery, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:
    Background: Congenital bilateral hallux valgus with associated absence or fusion of the interphalangeal joint is a classic diagnostic feature of fibrodysplasia ossificans progressiva (FOP), a human genetic disease of extra-skeletal bone formation caused in nearly all cases by a gain-of-function mutation in Activin A Receptor I/Activin-like Kinase 2 (ACVR1/ALK2), which encodes a bone morphogenetic protein (BMP) Type 1 receptor. This toe malformation prompts the suspicion of FOP even before the appearance of extra-skeletal bone. Here we report the case of a four-month-old child who was suspected of having FOP on the basis of a great toe malformation identical to that seen in children with the disease. Read More

    A cumulative analogue joint involvement scale (CAJIS) for fibrodysplasia ossificans progressiva (FOP).
    Bone 2017 Aug 29;101:123-128. Epub 2017 Apr 29.
    Department of Medicine, Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, United States. Electronic address:
    Background: Fibrodysplasia ossificans progressiva (FOP) is a catastrophic genetic disorder of progressive heterotopic ossification (HO). Assessment of functional mobility in FOP will be essential to support clinical trials of investigational agents.

    Results: Of necessity, we developed a simple, rapidly-administered, cumulative analogue joint involvement scale (CAJIS) for FOP based on assessments in 144 individuals worldwide with classic FOP. Read More

    Conserved signaling pathways underlying heterotopic ossification.
    Bone 2017 Apr 25. Epub 2017 Apr 25.
    School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China; Department of Medical Laboratory Science, Bengbu Medical College, Bengbu 233030, China; Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address:
    Heterotopic ossification (HO), a serious disorder of extra-skeletal bone formation, occurs as a common complication of trauma or in rare genetic disorders. Many conserved signaling pathways have been implicated in HO; however, the exact underlying molecular mechanisms for many forms of HO are still unclear. The emerging picture is that dysregulation of bone morphogenetic protein (BMP) signaling plays a central role in the process, but that other conserved signaling pathways, such as Hedgehog (HH), Wnt/β-catenin and Fibroblast growth factors (FGF), are also involved, either through cross-talk with BMP signaling or through other independent mechanisms. Read More

    [Transverse reductional anomaly and atypical fibrodysplasia ossificans progressiva: A case diagnosed late].
    Arch Pediatr 2017 Jun 14;24(6):547-551. Epub 2017 Apr 14.
    Service de pédiatrie générale multidisciplinaire, hôpital Estaing, CHU Clermont-Ferrand, 1, place Lucie-Aubrac, 63003 Clermont-Ferrand, France.
    Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by the association of congenital bone abnormalities and extraskeletal ossification flare-ups occurring in muscles and fasciae. Early diagnosis is important to prevent ossification flare-ups, but some atypical presentations can lead to errors in diagnosis and therefore delay. Here, we report on a case of an atypical presentation of FOP in a girl, in whom prominent transverse reductional abnormalities delayed diagnosis. Read More

    Anaesthetic management of a child with stone man syndrome: Look before you leap!
    Indian J Anaesth 2017 Mar;61(3):266-268
    Department of Onco.Anaesthesia and Palliative Medicine, Dr. BRAIRCH, AIIMS, New Delhi, India.
    Stone Man syndrome or fibrodysplasia ossificans progressiva (FOP) is an extremely rare (1 in 2 million) genetic disorder characterised by ectopic ossification of the skeletal and connective tissues leading to progressive fusion of axial and appendicular skeleton. Surgery and anaesthesia-induced trauma can lead to disease flare-up if due precautions are not taken and disable the patient further. However, rarity of the disease may lead to its common misdiagnosis and anaesthesiologist may be caught unaware. Read More

    A Zebrafish Model of Human Fibrodysplasia Ossificans Progressiva.
    Zebrafish 2017 Aug 10;14(4):293-304. Epub 2017 Apr 10.
    1 Program in Cell, Molecular, and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine , Boston, Massachusetts.
    Fibrodysplasia ossificans progressiva (FOP) is a rare, autosomal dominant genetic disorder in humans characterized by explosive inflammatory response to injury leading to gradual ossification within fibrous tissues, including skeletal muscle, tendons, and ligaments. A variety of animal models are needed to study and understand the etiology of human FOP. To address this need, here we present characterizations of the first adult zebrafish model for FOP. Read More

    Restricted Mandibular Movement Attributed to Ossification of Mandibular Depressors and Medial Pterygoid Muscles in Patients With Fibrodysplasia Ossificans Progressiva: A Report of 3 Cases.
    J Oral Maxillofac Surg 2017 Sep 16;75(9):1891-1898. Epub 2017 Mar 16.
    Professor, Dental and Oral Medical Center, Kurume University School of Medicine, Kurume, Japan.
    Fibrodysplasia ossificans progressiva (FOP) is an extremely rare genetic condition characterized by congenital malformation and progressive heterotopic ossification (HO) caused by a recurrent single nucleotide substitution at position 617 in the ACVR1 gene. As the condition progresses, HO leads to joint ankylosis, breathing difficulties, and mouth-opening restriction, and it can shorten the patient's lifespan. This report describes 3 cases of FOP confirmed by genetic testing in patients with restricted mouth opening. Read More

    Myositis ossificans in children: a review.
    Eur J Orthop Surg Traumatol 2017 May 9;27(4):491-502. Epub 2017 Mar 9.
    Emeritus Professor of Pediatric Surgery, Aristotle University of Thessaloniki, "G. Gennimatas" Hospital, Thessaloniki, Greece.
    The formation of lamellar bone in the soft tissues, where bone normally does not exist, is called myositis ossificans. However, it would be more accurate to describe as myositis ossificans the involvement of skeletal muscles and as ectopic or heterotopic ossification the involvement of soft tissues in general. The lesion is subdivided in genetic and non-genetic or acquired types. Read More

    The Rare Bone Disease Working Group: report from the 2016 American Society for Bone and Mineral Research Annual Meeting.
    Bone 2017 Sep 20;102:80-84. Epub 2017 Jan 20.
    Division of Endocrinology and Metabolism and the Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, United States.
    A working group on rare bone diseases was held in Atlanta, Georgia as part of the 2016 annual meeting of the American Society for Bone and Mineral Research. The meeting was organized by Matthew Drake. Given recent advances in our understanding of fibrodysplasia ossificans progressiva (FOP), the initial portion of the program was devoted to basic, translational, and clinical aspects of FOP. Read More

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