919 results match your criteria Fibrodysplasia Ossificans


Post-COVID-19 exacerbation of fibrodysplasia ossificans progressiva with multiple flare-ups and extensive heterotopic ossification in a 45-year-old female patient.

Rheumatol Int 2021 Jun 10. Epub 2021 Jun 10.

Department of Rheumatology, Physical and Rehabilitation, Medicine University Hospital Center "Sestre Milosrdnice", Zagreb, Croatia.

Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable course characterized by occasional flare-ups of heterotopic ossification (HO) in soft tissues that are followed by swelling, stiffness, pain and warmth. Here, we report for the first time a case of a 45-year-old female patient with known FOP recovering from COVID-19 with disease progression potentially linked with the viral illness. In December 2020 the patient contracted a mild form of COVID-19 infection without need for hospital admission. Read More

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Surgical and Radiological Management of Complicated Uterine Leiomyoma Aided by 3D Models in a Patient with Fibrodysplasia Ossificans Progressiva.

Am J Case Rep 2021 Jun 10;22:e931614. Epub 2021 Jun 10.

Department of Anesthesiology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.

BACKGROUND Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of the connective tissue. Over time, patients with FOP experience decreased range of motion in the joints and the formation of a second skeleton, limiting mobility. Patients with FOP are advised to avoid any unwarranted surgery owing to the risk of a heterotopic ossification flare-up. Read More

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Off-on-off-on use of imatinib in three children with fibrodysplasia ossificans progressiva.

Bone 2021 May 19;150:116016. Epub 2021 May 19.

The Department of Medicine, The Mayo Clinic, Rochester, MN 55905, United States of America. Electronic address:

The compassionate use of available medications with unproven efficacy is often in conflict with their clinical evaluation in placebo-controlled clinical trials. For ultra-rare diseases where no approved treatments exist, such as fibrodysplasia ossificans progressiva (FOP), routine clinical trial enrollment for available medications may be difficult to achieve. Therefore adaptive methods of evaluation are often desirable. Read More

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Pathogenic ACVR1 activation by Activin A-induced receptor clustering and autophosphorylation.

EMBO J 2021 May 18:e106317. Epub 2021 May 18.

Developmental Signalling Laboratory, The Francis Crick Institute, London, UK.

Fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG) are debilitating diseases that share causal mutations in ACVR1, a TGF-β family type I receptor. ACVR1 is a frequent mutation in both diseases. Pathogenic signaling via the SMAD1/5 pathway is mediated by Activin A, but how the mutation triggers aberrant signaling is not known. Read More

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New insights on fibrodysplasia ossificans progressiva: discussion of an autoptic case report and brief literature review.

Intractable Rare Dis Res 2021 May;10(2):136-141

Department of Public Health, Experimental and Forensic Medicine, Forensic Science Section "Antonio Fornari", University of Pavia, Pavia, Italy.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition with soft tissue progressive ossification, leading to severe disability. We describe a 27-years-old female affected by FOP who died after a fall. An autopsy was performed. Read More

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Nonclassic fibrodysplasia ossificans progressiva: A child from Angola with an ACVR1 variant.

Am J Med Genet A 2021 May 11. Epub 2021 May 11.

Departments of Orthopaedic Surgery, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Little is known about FOP in Africa and few cases of nonclassic fibrodysplasia ossificans progressiva (FOP) have been reported on the continent. Here we report a three-year-old girl from Angola with a nonclassic FOP clinical presentation that is characterized by complex malformations of the toes and fingers, reduction defects of the digits, absence of nails, progressive heterotopic ossification, and a confirmed heterozygous ACVR1 variant at c.983G > A. Read More

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Compartment Syndrome of the Thigh in a Patient with Fibrodysplasia Ossificans Progressiva.

J Orthop Case Rep 2020 May-Jun;10(3):103-107

Department of Medicine, The Mayo Clinic, Rochester, MN 55905, USA.

Introduction: The severe pain that commonly accompanies appendicular flare-ups of fibrodysplasia ossificans progressiva (FOP) is often ascribed to compartment syndrome, but no documentation exists.

Case Report: We revisited the case of an adult with classic FOP who underwent measurement of compartment pressure of the thigh during an acute, severely painful flare-up of the thigh. The intracompartmental pressure of the thigh was measured at 95--110 mm of mercury (normal compartment pressure is 0--8 mmHg). Read More

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Clinical, radiological, and molecular diagnosis of progressive fibrodysplasia ossificans.

Bol Med Hosp Infant Mex 2021 May 3. Epub 2021 May 3.

Departamento de Genética, Unidad Médica de Alta Especialidad Hospital de Pediatría Dr. Silvestre Frenk Freund, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico.

Background: Progressive fibrodysplasia ossificans is a rare genetic disease with heterozygous mutations (autosomal dominant inheritance) in the ACVR1 gene, which causes progressive heterotopic ossification in muscles, tendons, and ligaments, usually secondary to trauma. The ossification foci generate pain, joint ankyloses, and restricted movement. Congenital shortening and medial deviation first metatarsal of the foot is a distinctive feature. Read More

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Spatial patterns of heterotopic ossification in fibrodysplasia ossificans progressiva correlate with anatomic temperature gradients.

Bone 2021 Apr 27;149:115978. Epub 2021 Apr 27.

Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of the Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Progressive heterotopic ossification (HO) is a hallmark of fibrodysplasia ossificans progressiva (FOP); however, this tissue transformation is not random. Rather, we noticed that HO in FOP progresses in well-defined but inexplicable spatial and temporal patterns that correlate precisely with infrared thermographs of the human body. FOP is caused by gain-of-function mutations in Activin A receptor type I (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor kinase. Read More

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Evolving Management of Fibrodysplasia Ossificans Progressiva.

J Pediatr 2021 May;232S:S9-S15

Center for Arts in Medicine, College of the Arts, University of Florida, Gainesville, FL.

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Improving the Diagnosis of Fibrodysplasia Ossificans Progressiva.

J Pediatr 2021 May;232S:S3-S8

Center for Arts in Medicine, College of the Arts, University of Florida, Gainesville, FL.

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Hardened Hope: Care Advances for Fibrodysplasia Ossificans Progressiva.

J Pediatr 2021 May;232S:S1-S2

Center for Arts in Medicine, College of the Arts, University of Florida, Gainesville, FL.

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Do Interactions of Vitamin D and BMP Signaling Hold Implications in the Pathogenesis of Fibrodysplasia Ossificans Progressiva?

Curr Osteoporos Rep 2021 Apr 14. Epub 2021 Apr 14.

Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, WMRB 1027, Atlanta, GA, 30232, USA.

Purpose Of Review: Fibrodysplasia ossificans progressiva (FOP) is a debilitating rare disease known for episodic endochondral heterotopic ossification (HO) caused by gain-of-function mutations in ACVR1/ALK2. However, disease severity varies among patients with identical mutations suggesting disease-modifying factors, including diet, may have therapeutic implications. The roles of vitamin D in calcium metabolism and chondrogenesis are known, but its effects on BMP signaling and chondrogenesis are less studied. Read More

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[Rare bone disorders and respective treatments].

Internist (Berl) 2021 May 29;62(5):486-495. Epub 2021 Mar 29.

Orthopädisches Zentrum für Muskuloskeletale Forschung, Universität Würzburg, Brettreichstr. 11, 97074, Würzburg, Deutschland.

Delineating the genetic background and the underlying pathophysiology of rare skeletal dysplasias enables a broader understanding of these disorders as well as novel perspectives regarding differential diagnosis and targeted development of therapeutic approaches. Hypophosphatasia (HPP) due to genetically determined Alkaline Phosphatase deficiency exemplifies this development. While an enzyme replacement therapy could be established for severe HPP with the prevailing bone manifestation, the clinical impact of not immediately bone-related manifestations just being successively understood. Read More

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Microarchitecture of Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva: An HR-pQCT Case Series.

Front Cell Dev Biol 2021 11;9:627784. Epub 2021 Mar 11.

Department of Internal Medicine Section Endocrinology, Amsterdam Bone Center, Amsterdam Movement Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

It is challenging to study heterotopic ossification (HO) in patients with fibrodysplasia ossificans progressiva (FOP) due to the contraindication of invasive techniques (, bone biopsies), which can trigger flare-ups. The aim of this case study was to assess mature HO at the microarchitectural level non-invasively with high-resolution peripheral quantitative computed tomography (HR-pQCT). Depending on the patient's mobility, HR-pQCT scans were acquired of peripherally located HO and standard distal radius and tibia regions in two FOP patients, a 33-year-old woman and a 23-year-old man, with the classical mutation (p. Read More

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Deterioration of pulmonary function: An early complication in Fibrodysplasia Ossificans Progressiva.

Bone Rep 2021 Jun 25;14:100758. Epub 2021 Feb 25.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Internal Medicine section Endocrinology, Amsterdam Movement Sciences, Amsterdam Bone Centre, de Boelelaan 1117, Amsterdam, the Netherlands.

Fibrodysplasia Ossificans Progressiva (FOP) is a genetic disease characterized by the formation of heterotopic ossification (HO) in connective tissues. HO first develops in the thoracic region, before more peripheral sites are affected. Due to HO along the thoracic cage, its movements are restricted and pulmonary function deteriorates. Read More

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Saracatinib is an efficacious clinical candidate for fibrodysplasia ossificans progressiva.

JCI Insight 2021 Apr 22;6(8). Epub 2021 Apr 22.

Centre for Medicines Discovery, University of Oxford, Oxford, United Kingdom.

Currently, no effective therapies exist for fibrodysplasia ossificans progressiva (FOP), a rare congenital syndrome in which heterotopic bone is formed in soft tissues owing to dysregulated activity of the bone morphogenetic protein (BMP) receptor kinase ALK2 (also known as ACVR1). From a screen of known biologically active compounds, we identified saracatinib as a potent ALK2 kinase inhibitor. In enzymatic and cell-based assays, saracatinib preferentially inhibited ALK2, compared with other receptors of the BMP/TGF-β signaling pathway, and induced dorsalization in zebrafish embryos consistent with BMP antagonism. Read More

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Challenges and Opportunities for Drug Repositioning in Fibrodysplasia Ossificans Progressiva.

Biomedicines 2021 Feb 19;9(2). Epub 2021 Feb 19.

Department of Cell and Chemical Biology, Cardiovascular Cell Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands.

Fibrodysplasia ossificans progressiva (FOP) is an ultrarare congenital disease that progresses through intermittent episodes of bone formation at ectopic sites. FOP patients carry heterozygous gene point mutations in activin A receptor type I , encoding the bone morphogenetic protein (BMP) type I serine/threonine kinase receptor ALK2, termed activin receptor-like kinase (ALK)2. The mutant ALK2 displays neofunctional responses to activin, a closely related BMP cytokine that normally inhibits regular bone formation. Read More

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February 2021

Fibrodysplasia ossificans progressiva in a young adult with genetic mutation: Case report.

Medicine (Baltimore) 2021 Mar;100(9):e24620

Department of Rheumatology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong.

Rationale: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by congenital skeletal deformities and soft tissue masses that progress into heterotopic ossification. Deformities of the great toes are distinctive and heterotrophic ossification usually begins in the first decade of the patient's life. Any invasive procedure could potentially trigger a flare and heterotopic calcification. Read More

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Novel bicyclic pyrazoles as potent ALK2 (R206H) inhibitors for the treatment of fibrodysplasia ossificans progressiva.

Bioorg Med Chem Lett 2021 Apr 18;38:127858. Epub 2021 Feb 18.

Drug Discovery Chemistry Platform Unit, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

Mutant activin receptor-like kinase-2 (ALK2) is associated with the pathogenesis of fibrodysplasia ossificans progressiva, making it an attractive target for therapeutic intervention. We synthesized a new series of bicyclic pyrazoles and evaluated their mutant ALK2 enzyme inhibitory activities, leading to the identification of 8 as the most potent inhibitor. This compound showed moderate microsomal metabolic stability and human ether-a-go-go related gene (hERG) safety. Read More

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Pain Phenotypes in Rare Musculoskeletal and Neuromuscular Diseases.

Neurosci Biobehav Rev 2021 May 10;124:267-290. Epub 2021 Feb 10.

Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA. Electronic address:

For patients diagnosed with a rare musculoskeletal or neuromuscular disease, pain may transition from acute to chronic; the latter yielding additional challenges for both patients and care providers. We assessed the present understanding of pain across a set of ten rare, noninfectious, noncancerous disorders; Osteogenesis Imperfecta, Ehlers-Danlos Syndrome, Achondroplasia, Fibrodysplasia Ossificans Progressiva, Fibrous Dysplasia/McCune-Albright Syndrome, Complex Regional Pain Syndrome, Duchenne Muscular Dystrophy, Infantile- and Late-Onset Pompe disease, Charcot-Marie-Tooth Disease, and Amyotrophic Lateral Sclerosis. Through the integration of natural history, cross-sectional, retrospective, clinical trials, & case studies we described pathologic and genetic factors, pain sources, phenotypes, and lastly, existing therapeutic approaches. Read More

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ALK2 Receptor Kinase Association with FKBP12.6 Is Structurally Conserved with the ALK2-FKBP12 Complex.

Biomedicines 2021 Jan 29;9(2). Epub 2021 Jan 29.

Centre for Medicines Discovery, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.

The immunophilin FKBP12 is a known inhibitor of type I BMP and TGF-β receptors that competes for binding with their substrate SMADs. FKBP12 and the close paralog FKBP12.6 additionally assemble with ryanodine receptors to control Ca release. Read More

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January 2021

Cardiopulmonary and Neurologic Dysfunctions in Fibrodysplasia Ossificans Progressiva.

Biomedicines 2021 Feb 5;9(2). Epub 2021 Feb 5.

Department of Medicine, Division of Endocrinology and Metabolism, the Institute for Human Genetics, and the Program in Craniofacial Biology, University of California, San Francisco, CA 94143, USA.

Fibrodysplasia Ossificans Progressiva (FOP) is an ultra-rare but debilitating disorder characterized by spontaneous, progressive, and irreversible heterotopic ossifications (HO) at extraskeletal sites. FOP is caused by gain-of-function mutations in the Activin receptor Ia/Activin-like kinase 2 gene (), with increased receptor sensitivity to bone morphogenetic proteins (BMPs) and a neoceptor response to Activin A. There is extensive literature on the skeletal phenotypes in FOP, but a much more limited understanding of non-skeletal manifestations of this disease. Read More

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February 2021

Genomic Context and Mechanisms of the Mutation in Fibrodysplasia Ossificans Progressiva.

Biomedicines 2021 Feb 5;9(2). Epub 2021 Feb 5.

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Sciences (DiNOGMI), University of Genova, 16100 Genova, Italy.

Basic research in Fibrodysplasia Ossificans Progressiva (FOP) was carried out in the various fields involved in the disease pathophysiology and was important for designing therapeutic approaches, some of which were already developed as ongoing or planned clinical trials. Genetic research was fundamental in identifying the FOP causative mutation, and the astonishing progress in technologies for genomic analysis, coupled to related computational methods, now make possible further research in this field. We present here a review of molecular and cellular factors which could explain why a single mutation, the R206H in the gene, is absolutely prevalent in FOP patients. Read More

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February 2021

Suppressed prefrontal cortex oscillations associate with clinical pain in fibrodysplasia ossificans progressiva.

Orphanet J Rare Dis 2021 01 30;16(1):54. Epub 2021 Jan 30.

Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Pain is a highly prevalent symptom experienced by patients across numerous rare musculoskeletal conditions. Much remains unknown regarding the central, neurobiological processes associated with clinical pain in musculoskeletal disease states. Fibrodysplasia ossificans progressiva (FOP) is an inherited condition characterized by substantial physical disability and pain. Read More

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January 2021

Heterotopic ossification on the volar surface of the distal radius in a child with fibrodysplasia ossificans progressiva: challenges in surgical excision of a rare condition.

Hand Surg Rehabil 2021 Apr 27;40(2):194-197. Epub 2021 Jan 27.

Acibadem Maslak Hospital, Department of Orthopedics and Traumatology, Darüşşafaka Büyükdere Caddesi No No:40, 34457 Sarıyer/Istanbul, Turkey.

Fibrodysplasia ossificans progressiva (FOP) is one of the genetic and developmental forms of heterotopic ossification. We report a case of FOP on the volar surface of the distal radius, located close to the median nerve and radial artery with neurologic symptoms secondary to median nerve entrapment. The patient underwent surgical excision of the heterotopic lesion followed by radiation therapy. Read More

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Augmented BMP signaling commits cranial neural crest cells to a chondrogenic fate by suppressing autophagic β-catenin degradation.

Sci Signal 2021 01 12;14(665). Epub 2021 Jan 12.

Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.

Cranial neural crest cells (CNCCs) are a population of multipotent stem cells that give rise to craniofacial bone and cartilage during development. Bone morphogenetic protein (BMP) signaling and autophagy have been individually implicated in stem cell homeostasis. Mutations that cause constitutive activation of the BMP type I receptor ACVR1 cause the congenital disorder fibrodysplasia ossificans progressiva (FOP), which is characterized by ectopic cartilage and bone in connective tissues in the trunk and sometimes includes ectopic craniofacial bones. Read More

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January 2021

Inhibitory effects of sesquiterpene lactones from the Indonesian marine sponge Lamellodysidea cf. herbacea on bone morphogenetic protein-induced osteoblastic differentiation.

Bioorg Med Chem Lett 2021 03 8;35:127783. Epub 2021 Jan 8.

Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan. Electronic address:

A new unique sesquiterpene lactone, bicyclolamellolactone A (1), was isolated together with two known monocyclofarnesol-type sesquiterpenes, lamellolactones A (2) and B (3), from the Indonesian marine sponge Lamellodysidea sp. (cf. L. Read More

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ActivinA Induced SMAD1/5 Signaling in an iPSC Derived EC Model of Fibrodysplasia Ossificans Progressiva (FOP) Can Be Rescued by the Drug Candidate Saracatinib.

Stem Cell Rev Rep 2021 Jun 7;17(3):1039-1052. Epub 2021 Jan 7.

Institute of Chemistry/Biochemistry, Thielallee 63, Freie Universität Berlin, 14195, Berlin, Germany.

Balanced signal transduction is crucial in tissue patterning, particularly in the vasculature. Heterotopic ossification (HO) is tightly linked to vascularization with increased vessel number in hereditary forms of HO, such as Fibrodysplasia ossificans progressiva (FOP). FOP is caused by mutations in the BMP type I receptor ACVR1 leading to aberrant SMAD1/5 signaling in response to ActivinA. Read More

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Symmetrical glial hyperplasia in the brainstem of fibrodysplasia ossificans progressiva.

Neuropathology 2021 Apr 6;41(2):146-151. Epub 2021 Jan 6.

Department of Neuropathology, Kyushu University, Fukuoka, Japan.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disease, characterized by the progressive ossification of skeletal muscles, fascia, tendons, and ligaments. In most cases, the great toes of patients show symmetrical congenital malformations. The causative gene for FOP has been identified as the activin A receptor, type 1 (ACVR1) gene (ACVR1). Read More

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