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The diagnosis of fibrodysplasia ossificans progressiva is missed or delayed because of its insidious precursors, especially in uncharacteristic cases. Fibrodysplasia ossificans progressiva, which mostly displayed the mutation c.617G > A, p.R206H, is characterized by congenital malformation of the great toe and progressive extra-skeletal ossification of ligaments, tendons and muscles. The mutation c.774G > C, p.R258S (HGVS: NC_000002.11:g.158626896 C > G) in activin A receptor type I is an infrequent etiology of fibrodysplasia ossificans progressiva and can present different clinical features. Awareness of these multiple clinical features will help endocrinologists in the early diagnosis of fibrodysplasia ossificans progressiva. We report a case of fibrodysplasia ossificans progressiva with the activin A receptor type I mutation c.774G > C, p.R258S, which was diagnosed before its ossifying period., (© 2024. The Author(s).)

Rationale: Myositis ossificans (MO) is characterized by benign heterotopic ossificans in soft tissues like muscles, which can be classified into nonhereditary MO and fibrodysplasia ossificans progressiva (FOP). Nonhereditary MO is characterized by ossification of the soft tissues after acute or repetitive trauma, burns, or surgical intervention. FOP is a rare and crippling disease characterized by congenital malformation of the big toe and heterotopic ossification in muscle. The majority of FOP's musculoskeletal traits are associated with dysregulated chondrogenesis. The diagnosis is mainly based on clinical manifestation, imaging examination, and genetic analysis. There is still no effective treatment to cure or slow its progression. The best approach remains early diagnosis, conservative drug treatment, and injury prevention to avoid local ossification., Patient Concerns: A 34-year-old male presented at our hospital because of trismus caused by ossification of the masseter muscle. In addition, he had serious stiffness and multiple bony masses throughout the body, which led to limited movement., Diagnoses: Based on the clinical manifestation of movement restriction, characteristic radiographic images of ossification of soft tissues, the genetic test showing a heterozygous molecule (c.974G > C, p.G325A) of the activin A receptor type I, the patient was diagnosed as FOP complicated with localized MO in masseter after trauma and infection., Interventions: The patient underwent the surgical resection of ossification in the masseter muscle, he was instructed to insist on mouth-opening exercises and take glucocorticoids and nonsteroidal anti-inflammatory medications after surgery., Outcomes: The symptoms of trismus are relieved, and eating can be basically achieved after surgery, while the symptoms of trismus recurred 2 years later., Lessons: Although FOP has unique clinical manifestations, its diagnosis may be difficult because of its rarity. Gene analysis is the main standard for diagnosis, while patients with different genotypic variations may show different clinical symptoms. Therapeutic interventions are still supportive and preventive, and surgery is not recommended except under certain circumstances., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of the Study: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant condition that leads to significant disability and morbidity, characterised by the formation of heterotopic hard tissues within connective tissues. The condition has an incidence of approximately one per two million people worldwide. There is no known single effective treatment available for FOP. We report the world's first case of a healthy infant born following in vitro fertilisation (IVF) and preimplantation genetic testing for monogenic disorder (PGT-M) using Karyomapping for FOP., Case Presentation: A 30-year-old Caucasian female with FOP presented with her partner seeking IVF with PGT-M to achieve a healthy pregnancy with an embryo unaffected by FOP., Methods: The couple underwent IVF and PGT-M using Karyomapping as the testing method. A multi-disciplinary team approach was utilised in planning this case, considering the additional risks of oocyte retrieval, pregnancy and childbirth in women with FOP., Main Findings: The oocyte retrieval was covered with a 5-day course of prednisolone to reduce the risk of a localised inflammatory reaction, which could result in subsequent heterotopic ossification. This was subsequently weaned down with reducing doses every two days. The patient underwent uncomplicated oocyte retrieval, yielding 12 mature oocytes. Following intracytoplasmic sperm injection (ICSI), ten zygotes having two pro-nuclei were cultured, and six underwent trophoectoderm biopsy and vitrification 5-6 days after retrieval. PGT-M via Karyomapping revealed four out of six (66.7%) of blastocysts were not carriers of the maternal high-risk FOP allele. In total, the patient had three separate embryo transfers. Pregnancy was achieved following the third frozen embryo transfer, which went to 37 weeks' gestation, and delivered by Caesarean section. The baby was born in excellent condition and is unaffected by FOP., Conclusion: IVF/ICSI and PGT-M using Karyomapping was successfully implemented to identify embryos carrying the high-risk FOP allele resulting in a healthy livebirth., (© 2024. The Author(s).)

Heterotopic ossification (HO) is a debilitating pathology where ectopic bone develops in areas of soft tissue. HO can develop as a consequence of traumatic insult or as a result of dysregulated osteogenic signaling, as in the case of the orphan disease fibrodysplasia ossificans progressiva (FOP). Traumatic HO (tHO) formation is mediated by the complex interplay of signaling between progenitor, inflammatory, and nerve cells, among others, making it a challenging process to understand. Research into the pathogenesis of genetically mediated HO (gHO) in FOP has established a pathway involving uninhibited activin-like kinase 2 receptor (ALK2) signaling that leads to downstream osteogenesis. Current methods of diagnosis and treatment lag behind pre-mature HO detection and progressive HO accumulation, resulting in irreversible decreases in range of motion and chronic pain for patients. As such, it is necessary to draw on advancements made in the study of tHO and gHO to better diagnose, comprehend, prevent, and treat both.

Background: Fibrodysplasia ossificans progressiva (FOP) as a rare and heritable disorder with the infrequent genetic transmission of the condition is a catastrophic disorder of heterotopic ossification (HO) and a cause of extraskeletal bone formation in humans. Given the lack of effective treatment for this disease, the important point is to avoid aggravating factors such as bone biopsy, surgery, and intramuscular injection., Case Presentation: In this report, we present a 52-year-old female patient, Kurdish ethnic, suspected to FOP who had a surgical intervention on the second toe of the right foot, which subsequently, it caused further deterioration of the disease in the person including necrosis and amputation of the distal phalanx of the second toe., Conclusions: Although, based on our investigation and the available scientific evidence, surgery may a cause for faster progression and worsening of the FOP disorder, but its proof requires further studies., (© 2023. The Author(s).)

Background: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, disabling genetic disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification of soft and connective tissues. Assiduous attention to the unmet needs of this patient community is crucial to prevent potential iatrogenic harm and optimize care for individuals with FOP., Objective: To gather international expert opinion and real-world experience on the key challenges for individuals with FOP and their families, highlight critical gaps in care, communication, and research, and provide recommendations for improvement., Methods: An international group of expert clinicians, patients and patient advocates, caregivers and representatives from the international FOP community participated in a virtual, half-day meeting on 22 March 2021 to discuss the key unmet needs of individuals with FOP., Results: Individuals with FOP often face the frustration of long diagnostic journeys, the burden of self-advocacy and the navigation of novel care pathways. Globally, patients with FOP are also confronted with inequities in access to diagnosis and specialist care, and consequently, unequal access to registries, clinical trials, and essential support from patient associations. Organizations such as the International FOP Association, the International Clinical Council on FOP, and national FOP organizations work to provide information, facilitate access to expert clinical guidance, nurture patient empowerment, fund FOP research and/or foster meaningful collaborations with the research community. The non-profit Tin Soldiers Global FOP Patient Search program aims to identify and provide a pathway to diagnosis and care for individuals with FOP, particularly in underserved communities. Such global initiatives and the increasingly widespread use of telemedicine and digital platforms offer opportunities to improve vital access to care and research., Conclusions: This multi-stakeholder perspective highlights some of the unmet needs of individuals with FOP and their families. Regional and international organizations play an important role in improving the quality of life of those they reach in the global FOP community. However, globally, fundamental issues remain around raising awareness of FOP among healthcare professionals, identifying individuals with FOP, reducing time to diagnosis, and ensuring access to best practice in care, support, and clinical research. Medical writing support was industry-sponsored., (© 2022. The Author(s).)

Background: COVID-19, caused by the SARS-CoV-2 virus, is a severe inflammatory condition. Patients with pre-existing conditions including diabetes, hypertension, and cardiovascular disease are at particularly high risk of complications. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare and debilitating genetic disorder that is characterized by a pro-inflammatory state, which leads to progressive heterotopic ossification and complications after trauma, including intramuscular vaccinations. To better understand the impact of COVID-19 on patients with FOP, we first examined the social impact of the pandemic using data from the FOP Registry managed by the International FOP Association. We also identified patients with FOP who were exposed to or contracted the SARS-CoV-2 virus, or who received a COVID-19 vaccine, to investigate if patients with FOP were at increased risks of complications from SARS-CoV2 exposure or vaccination., Results: Data from 326 individuals in 69 countries in the International FOP Association FOP Connection Registry were examined using patient-reported outcomes measurement information system (PROMIS) global health scale scores. Twenty-six (28.9%) participants aged ≥ 15 years old rated their satisfaction with their social activities and relationships as poor in 2020, which was an increase from 18 (18.9%) in 2019, prior to the SARS-CoV-2 outbreak. Similar trends were noted for physical and mental health in the pediatric population. Frequency of physician visits was not changed, but a larger portion of patients reported missing dental visits in 2020 compared with 2019 (31.5% vs. 41.7%). A second cohort with 32 subjects was tracked after SARS-CoV-2 exposure or vaccination. Ten subjects were positively diagnosed with COVID-19, 15 received a COVID-19 vaccine, and seven had high-risk SARS-CoV-2 exposure but either did not have a confirmed clinical diagnosis or tested negative. Subjects who tested positive for the virus showed no major complications or increased FOP disease activity, though our sample size is very limited. Among the 15 subjects who received a COVID-19 vaccine, using the International Clinical Council on FOP guidelines for prophylaxis with ibuprofen or acetaminophen, only one person experienced flare-like activity at the injection site., Conclusions: Patients with FOP showed a significant decrease in social activities that was reflective of the isolation and mobility changes in this debilitated population. In our limited cohort, the majority of the patients with FOP who tested positive for COVID-19 showed no major complications. Also, although limited in sample size, the majority of patients who received a COVID-19 vaccination and followed guidelines from the FOP International Clinical Council tolerated vaccination well. Only one person experiencing flare activity following their injection. Thus, the risks and benefits of COVID-19 vaccination needs to be discussed carefully so as to support informed decisions., (© 2022. The Author(s).)

Background: Myositis ossificans progressiva (MOP) is a low prevalence hereditary connective tissue disease (1:2,000,000 habitants). It is characterized by heterotopic ossification with an uncertain behavior that has been exceptionally related to neoplasms. The objective was to know the coexistence of MOP with neoplasms of mesodermal origin, so that they can be considered in the diagnosis of other patients, as well as formulate hypotheses to clarify their association., Clinical Case: 27-year-old female with right gluteal and ischitiobial muscle pain that increased with exercise, without remission with analgesics until limiting the mobility of both extremities. A bone series was requested where areas of heterogeneous radiolucency were evidenced in the region of, both, thighs and pelvis in an irregular manner, similar to bone density, which was compatible with the ultrasound and tomographic findings; we concluded that they were images of myositis ossificans of the hip. The patient reported gastric symptoms and an endoscopy was requested, which histopathologically reported diffuse gastric carcinoma with signet ring cells; cabinet images showed an ovarian tumor., Conclusion: MOP is a low prevalence disease, which is why its knowledge and suspicion are essential for the diagnosis. We found little literature that involves the three entities; therefore, their pathophysiology and understanding is limited. Regarding MOP, at this moment there is no curative treatment; however, an accurate diagnosis allows to start rehabilitation in a timely manner with an improvement in the quality of life., (© 2022 Revista Medica del Instituto Mexicano del Seguro Social.)

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare progressive genetic disease effecting one in a million individuals. During their life, patients with FOP progressively develop bone in the soft tissues resulting in increasing immobility and early death. A mutation in the ACVR1 gene was identified as the causative mutation of FOP in 2006. After this, the pathophysiology of FOP has been further elucidated through the efforts of research groups worldwide. In 2015, a workshop was held to gather these groups and discuss the new challenges in FOP research. Here we present an overview and update on these topics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Ruiter, Smilde, Pals, Bravenboer, Knaus, Schoenmaker, Botman, Sánchez-Duffhues, Pacifici, Pignolo, Shore, van Egmond, Van Oosterwyck, Kaplan, Hsiao, Yu, Bocciardi, De Cunto, Longo Ribeiro Delai, de Vries, Hilderbrandt, Jaspers, Keen, Koolwijk, Morhart, Netelenbos, Rustemeyer, Scott, Stockklausner, ten Dijke, Triffit, Ventura, Ravazzolo, Micha and Eekhoff.)

Background: Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine-Serine rich domain and causing the hyper-activation of the receptor and the responsivity to the non-canonical ligand, Activin A. In the present study, we described a 3-years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution., Methods: Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection-based assays., Results and Conclusions: We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A>T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A-mediated signaling, as observed for the gene variants associated with FOP., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

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. This report aimed to present an educational value case of a patient with clinical, imaging, and molecular diagnosis of progressive fibrodysplasia ossificans, recognized as a rare condition that severely affects the quality of life., Case Report: We present the case of a 6-year-old female patient with lumps in the right scapular and dorsal region, progressive joint rigidity, and short first metatarsal medially deviated since birth. By imaging studies, we established the diagnosis of progressive fibrodysplasia ossificans. Sanger sequencing of ACVR1 reported c.617G>A (p.Arg206His)., Conclusions: Confirmation of the diagnosis allowed genetic counseling, including a comprehensive explanation of the disease's natural history and measures to prevent its rapid progression.

Heterotopic ossification (HO) is a disorder characterised by the formation of ectopic bone in soft tissue. Acquired HO typically occurs in response to trauma and is relatively common, yet its aetiology remains poorly understood. Genetic forms, by contrast, are very rare, but provide insights into the mechanisms of HO pathobiology. Fibrodysplasia ossificans progressiva (FOP) is the most debilitating form of HO. All patients reported to date carry heterozygous gain-of-function mutations in the gene encoding activin A receptor type I (ACVR1). These mutations cause dysregulated bone morphogenetic protein (BMP) signalling, leading to HO at extraskeletal sites including, but not limited to, muscles, ligaments, tendons and fascia. Ever since the identification of the causative gene, developing a cure for FOP has been a focus of investigation, and studies have decoded the pathophysiology at the molecular and cellular levels, and explored novel management strategies. Based on the established role of BMP signalling throughout HO in FOP, therapeutic modalities that target multiple levels of the signalling cascade have been designed, and some drugs have entered clinical trials, holding out hope of a cure. A potential role of other signalling pathways that could influence the dysregulated BMP signalling and present alternative therapeutic targets remains a matter of debate. Here, we review the recent FOP literature, including pathophysiology, clinical aspects, animal models and current management strategies. We also consider how this research can inform our understanding of other types of HO and highlight some of the remaining knowledge gaps., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Rationale: Fibrodysplasia ossificans progressiva (FOP) is rare genetic disease featuring progressive heterotopic ossification of soft tissues of the musculoskeletal system which leads to severe disability and premature death. Recognition of this disease is important since invasive diagnostic procedures can promote disease progression. However, despite its distinctive clinical manifestations, diagnosis can be difficult because of its rarity PATIENT CONCERNS:: A 20-year-old woman was referred to rheumatology clinic for management of "ankylosing spondylitis". The patent had begun to have hard subcutaneous nodules when she was 1 year old, and subsequently developed hip joint pain and flexion contractures of knees and hips leading to disability., Diagnoses: Based on characteristic bilateral great toe deformities and radiographic images of ossification of soft tissues, a clinical diagnosis of FOP was made. This was confirmed by genetic test showing a heterozygous mutation (c.G617A) of the activin receptor 1A gene (ACVR1)., Interventions: The patient was treated symptomatically and with supportive measures, and her condition remained stable., Lessons: Diagnosis of FOP can be difficult, despite its distinctive clinical manifestations, because of its rarity. Recognition of this disease is important to avoid invasive diagnostic procedures which can promote progression.

Background: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by extraskeletal heterotopic ossification. It is well recognized that FOP can lead to a devastating condition of disability. However, the mortality rate of FOP patients in China and risk factors for mortality are still largely unclear., Methods: We conducted a retrospective research on a cohort of 65 cases of FOP patients in China from 2008 to 2018. We reviewed medical records of these FOP patients to retrieve information such as date of birth/death, gender, clinical features, genotypes and biochemical parameters and analyze the correlation of these parameters with the mortality., Results: 92.3% (60/65 cases) patients were classic FOP patients, 3.1% (2/65 cases) were FOP-plus and 4.6% (3/65 cases) were FOP variants. 9 cases of this cohort were dead during the ten-year period, and the overall mortality rate was 13.8%. c.617G > A mutation was confirmed in all non-survivors. In FOP patients≤18 years at diagnosis, non-survivors demonstrated significantly lower blood osteocalcin and alkaline phosphatase levels compared with survivors (P < 0.05), and spearman correlation and logistic regression analysis indicated that serum osteocalcin and alkaline phosphatase levels were negatively correlated with the mortality. Furthermore, the receiver-operating characteristic curve analysis showed serum osteocalcin had the largest area under the curve of 0.855 among four biochemical parameters, and serum osteocalcin < 65.9 ng/ml displayed a good capacity to discriminate the non-survivors from survivors in FOP patients aged 18 years and younger at diagnosis., Conclusions: Our findings showed that the mortality rate of FOP was 13.8% in China. Serum OC level was negatively correlated with the mortality in Chinese FOP patients ≤18 years at diagnosis.

Background: Fibrodysplasia ossificans progressiva (FOP) is the most catastrophic form of heterotopic ossification, due to ongoing intracellular signaling through the bone morphogenic protein pathway. The paroxysmal appearance of inflammatory lumps and elevated inflammatory markers during flares, suggest that FOP is an auto-inflammatory disease. Based on evidence, demonstrating a role for interleukin-1β (IL-1β) in other forms of heterotopic ossification, we hypothesized that treating FOP patients with anti-IL-1 agents could help lower the rate of FOP paroxysms and/or limit the symptoms and residual lesions., Case Presentation: A 13.5-year-old Arab boy was diagnosed with FOP. Treatment with anti-inflammatory drugs did not change the disease course. New lumps appeared in a rate of approximately one every 8 days. Treatment with the anti-IL-1 agents anakinra and canakinumab resulted in significantly lower rate of paroxysms (every 22-25 days, of which almost all involved only 2 existing lumps), as well as shorter duration. High levels of IL-1β were found in the patient's plasma samples, collected during a paroxysm that appeared 8 weeks after the last canakinumab dose. In contrast, IL-1β plasma levels were undetectable in the previous three plasma samples, obtained while he was treated with anti-IL-1 agents., Conclusions: Our data demonstrate the efficacy of anti-IL-1 agents in the treatment of a patient with FOP. Results showing the marked increase in IL-1β plasma levels during a paroxysm support a role for IL-1β in the pathogenesis of FOP and further provide the rationale for the use of anti-IL-1 agents in FOP treatment.

Background: Fibrodysplasia ossificans progressiva is an ultrarare autosomal dominant disorder and disabling syndrome characterized by postnatal progressive heterotopic ossification of the connective tissue and congenital malformation of the big toes. Fibrodysplasia ossificans progressiva has worldwide prevalence of about 1 in 2 million births. Nearly 90% of patients with fibrodysplasia ossificans progressiva are misdiagnosed and mismanaged and thus undergo unnecessarily interventions. So far, the number of reported existing cases worldwide is about 700. Clinical examination, radiological evaluation, and genetic analysis for mutation of the ACVR1 gene are considered confirmatory tools for early diagnosis of the disease. Association of fibrodysplasia ossificans progressiva with heterotopic ossification is well documented; however, postsurgical exaggerated response has never been reported previously, to the best of our knowledge., Case Presentation: We report a case of a 10-year-old Pakistani boy brought by his parents to our institution. He had clinical and radiological features of fibrodysplasia ossificans progressive and presented with multiple painful lumps on his back due to hard masses and stiffness of his shoulders, neck, and left hip. He underwent surgical excision of left hip ossification followed by an exaggerated response in ossification with early disability. Radiological examination revealed widespread heterotopic ossification. All of his laboratory blood test results were normal., Conclusion: Fibrodysplasia ossificans progressiva is a very rare and disabling disorder that, if misdiagnosed, can lead to unnecessary surgical intervention and disastrous results of early disability. We need to spread knowledge to physicians and patients' family members about the disease, as well as its features for early diagnosis and how to prevent flare-up of the disease to promote better quality of life in these patients.

Clinical trials for orphan diseases are critical for developing effective therapies. One such condition, fibrodysplasia ossificans progressiva (FOP; MIM#135100), is characterized by progressive heterotopic ossification (HO) that leads to severe disability. Individuals with FOP are extremely sensitive to even minor traumatic events. There has been substantial recent interest in clinical trials for novel and urgently-needed treatments for FOP. The International Clinical Council on FOP (ICC) was established in 2016 to provide consolidated and coordinated advice on the best practices for clinical care and clinical research for individuals who suffer from FOP. The Clinical Trials Committee of the ICC developed a focused list of key considerations that encompass the specific and unique needs of the FOP community - considerations that are endorsed by the entire ICC. These considerations complement established protocols for developing and executing robust clinical trials by providing a foundation for helping to ensure the safety of subjects with FOP in clinical research trials., (© 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction: Myositis ossificans (MO) is an ectopic ossification characterized by an appearance of bone formation predominantly in muscle tissue. Trauma is the most common etiological factor, observed in almost 60-75% of cases, whereas a non-traumatic MO is rarely described in the literature. A diagnosis is based on clinical and radiological findings., Presentation of Case: A 75-year old female patient has been admitted to our clinic with a localized swelling of the posterior femoral compartment, presented on magnetic resonance as a calcification in the biceps femoris muscle. Laboratory test results were within the normal range. Surgical procedure consisted of excision of the tumor mass with primary wound reconstruction and drainage. The post-operative period was uneventful, and the patient was discharged from hospital on the seventh postoperative day. The pathohistology findings have shown the MO., Discussion: A non-traumatic MO is scarcely described in the literature. A chronic microtrauma, tissue ischaemia and inflammation are listed as causal mechanisms of a non-traumatic MO. MO non-traumatica occurs more often in patients with a parallel, subdural or epidural haemorrhage and a hip surgery. Our case did not present any family history, trauma or associated anomalies of hands or fingers., Conclusion: Myositis ossificans should be considered as the differential diagnosis of all soft tissue tumor masses, even if known risk factors are not present in the anamnesis. Surgery is a reasonable therapeutic strategy in the presence of a tumor mass in soft tissues, and definite diagnosis can be set only based on pathohistological findings., Key Words: Ectopic ossification, Non traumatic myositis, Surgery.

Background: Myositis ossificans describes a heterotopic bone formation within a muscle. Thereby myositis ossificans is classified in two different groups: myositis ossificans progressiva (MOP) which describes a genetic autosomal dominant rare disease and myositis ossificans traumatica (MOT). The exact pathogenesis of MOT is unclear. The aim of this article was to analyse and interpret the existing literature reporting MOT of masticatory muscles and compare the results with our own clinical experience with MOT. Risk-factors, etiology, clinical features, diagnostic imaging, as well as different treatment options were evaluated and recommendations for the prevention, diagnosis, and therapy of MOT of the masticatory muscles were given., Methods: Following the PRISMA-Guidelines, a systematic search within the PubMed/Medline database with a view to record literature of MOT of the masticatory muscles was performed. Furthermore, the database of our own clinic was screened for cases of MOT., Results: In total, 63 cases of MOT of the masticatory muscles which were reported in English-based literature were included in this study. Overall, 25 female and 37 male patients could be analysed whereas one patient's gender was unknown. Complication of wisdom-tooth infection (n = 3) as well as the results of dental procedures like dental extraction (n = 7), mandibular nerve block (n = 4), periodontitis therapy (n = 1) were reported as MOT cases. From the 15 reported cases that appeared after dental treatment like extraction or local anesthesia the medial pterygoid (n = 10) was the most affected muscle. Hereof, females were more affected (n = 9) than males (n = 6). The most reported clinical symptom of MOT was trismus (n = 54), followed by swelling (n = 17) and pain (n = 13). One clinical case provided by the authors was detected., Conclusions: Dental procedures, such as local anesthesia or extractions, may cause MOT of the masticatory musculature. Demographical analyses demonstrate that females have a higher risk of developing MOT with respect to dental treatment. The most important treatment option is surgical excision. Subsequent physical therapy can have beneficial effects. Nevertheless, a benefit of interpositional materials and drugs as therapy of MOT of the masticatory muscles has not yet been proven. Myositis ossificans progressiva has to be excluded.

Background: Fibrodysplasia ossificans progressiva (FOP), also known as Myositis ossificans progressiva or Munchmeyer's disease, is an extremely rare and disabling genetic condition of congenital skeletal malformations and progressive heterotopic ossification (HO). The disease is characterized by congenital skeletal anomalies and progressive ectopic bone formation in connective tissues such as ligaments, muscles and tendons. The disease has an incidence of about 1 in 2 million population., Case Details: We report a case of a 2-year and 8-month old male child with an initial diagnosis of soft tissue sarcoma based on fine needle aspiration (FNAC) of neck swelling., Conclusion: Fibroplasia ossificans progressive (FOP) characteristically manifests with bilateral malformation of the great toe and progressive heterotopic ossification (HO). Clinicians and radiologists should be aware of these to prevent permanent disability.

Myositis ossificans circumscripta (MOC) is a rare benign condition characterized by heterotopic ossification occurring in the soft tissues. We report the case of a 15-year old patient complaining of mixed hip pain. No trauma has been reported during the interview. The joint had inflammation appearance and a non-mobilizing swelling adhered to the deeper structure with parietal projection over the groin fold. Radiographs of the hip showed a thickening of the soft tissues of the hip and some periarticular calcifications with unclear appearance. Excisional biopsy of the calcifications was decided and performed. Diagnosis was confirmed by histological examination of the surgical specimen. At six months follow-up the patient was very satisfied with his functional results. Returning to school sports was authorized. The patient had successful outcome.

Çakan M, Aktay-Ayaz N, Karadağ ŞG, Keskindemirci G. An extreme entity in differential diagnosis of musculoskeletal involvement-fibrodysplasia ossificans progressiva: a case based review. Turk J Pediatr 2018; 60: 593-597. Fibrodysplasia ossificans progressiva is one of the most devastating disorder of mankind characterized by progressive heterotopic ossification. Apart from hallux valgus, other symptoms start to develop in the first decade of life. The initial symptoms are tumefactive lesions on the back that gives an impression of benign or malignant tumoral lesion. It may cause restricted motion of the neck and shoulders and magnetic resonance imaging of the lesions may be reported as myositis or myofasciitis and these children may be referred to rheumatologists. Currently there is no definitive treatment of the disease but the most important issue in these patients is `primum non nocere`, because any invasive procedure could potentially trigger a flare and heterotopic calcification. Herein, we present a young case of fibrodysplasia ossificans progressiva to remind the typical signs and symptoms of the disease to all clinicians caring for children.

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. Due to the relation between the disease flares and the premenstrual period, the patient was put into a chemically induced amenorrhea, with no new inflammatory crises since.This case illustrates the importance of an accurate diagnosis to prevent unnecessary diagnostic procedures, as well as the need to develop specific treatment strategies to address each patient's particular needs., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

We report a case of a 29-year-old man who had been a victim of a public road accident. Four weeks later, the patient developed an isolated right thigh mass located ventrally in the distal one-third of the thigh. The mass was painful and associated with fever and inflammatory syndrome. Plain radiographs showed a bilateral calcified thickening of soft tissues with well-defined bony margins. Ultrasound objectified diffuse calcifications of soft tissues.CT scan-confirmed the diagnosis of myositis ossificans circumscripta, showing a bilateral thickening of the vastus intermedius chief of the quadriceps dotted with calcifications, extending along the femur axis. These calcifications have well-defined bony margins separated from the periosteum by a lucent zone., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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., Methods: The patient's genomic DNA of the coding region of ACVR1 was sequenced and analyzed for mutations known to cause FOP and novel mutations. Subsequent comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) analyses were performed to detect mutations elsewhere in the genome., Results: Genetic testing exonerated ACVR1 as culpable for the patient's toe malformation. CGH and SNP analyses identified a large intragenic deletion in a different BMP Type 1 receptor gene, BMP Receptor 1B/Activin-like kinase 6 (BMPR1B/ALK6), a gene associated with a variable spectrum of autosomal dominant brachydactyly phenotypes., Conclusions: This report illustrates that while toe morphology remains the earliest indicator of FOP, toe morphology alone is not an unequivocal clinical diagnostic feature of FOP, and supports that embryonic development of the great toe is highly sensitive to dysregulated signaling from at least two BMP type I receptors., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

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. In order to understand if there was worldwide consensus among clinicians treating FOP patients, an expert panel of physicians directly involved in FOP patient care was convened. Using a modified Delphi method, broad international consensus was reached on four main topics: diagnosis, prevention of flare-ups, patient and family-centered care and general clinical management issues. This study of physician preferences provides a basis for standardization of clinical management for FOP.

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., Competing Interests: Conflict of interest: None declared

Myositis ossificans progressiva (MOP) is an autosomal dominant disorder. There is a progressive ectopic ossification and skeletal malformation, mainly in the connective tissue of muscle. The diagnosis is based on the clinical findings and radiological demonstration of the skeletal malformations. A 38-year-old female patient was admitted to our department with progressive increase of the thigh. Results of laboratory studies were normal. The radiography of the right thigh showed multiple intramuscular calcifications. Myositis ossificans progressiva should be diagnosed as early as possible and non-invasively, based upon history, clinical and radiological findings. Early and correct diagnosis is fundamental for indication of proper management of the disease., Competing Interests: The authors declare no conflict of interest.

Myositis ossificans circumscripta (MOC) is a rare condition characterized by nontumoral heterotopic ossification of the soft tissues. This condition affects young subjects, occurring mainly after trauma. It is ubiquitous, predominantly located in girdles and limbs. We report the case of a young patient with paravertebral MOC without traumatic context; the aim of this study was to recall diagnostic criteria and imaging aspects.

Fibrodysplasia ossificans progressiva is a rare disorder of heterotopic ossification. Procedures like biopsy and surgery are known to be aggravating factors in promoting heterotopic ossification Clues to clinical diagnosis may therefore be a great advantage to treating orthopedician. Valgus deformity of great toe is an important diagnostic clue for treating physicians and thus aids in preventing the clinicians from subjecting the patients to unnecessary invasive and traumatic procedures. Hence clinical clues to early diagnosis are important in establishing the correct diagnosis and directing future management.

Fibrodysplasia ossificans progressiva is a rare autosomal dominantly inherited disorder of connective tissue caused by mutations in the gene encoding for ACVR1/ALK2, a bone morphogenetic protein type I receptor. It is mainly characterized by congenital malformations of the great toes and the formation of qualitatively normal bone in extra-skeletal sites leading to severe disability and eventually death. We present a sporadic case from Northern Tanzania with a minor unilateral hallux anomaly and the common ACVR1 c.617G>A mutation.

A young soccer player was diagnosed with myositis ossificans 6 weeks after a muscle strain in the right thigh. Radiographic and sonographic investigations initially helped to confirm diagnosis and later supported clinical improvement. We present our approach to the case and discuss pathophysiology, prevention and treatment of this rare condition., (2015 BMJ Publishing Group Ltd.)

Fibrodysplasia Ossificans Progressiva (FOP) is a rare debilitating disorder characterized by congenital deformity of the great toes from infancy and postnatal heterotopic ossification. Activating mutations in the activin A receptor type 1 (ACVR1) gene are responsible for the disease. The most common allelic variant leading to FOP is c.617 G>A; p.R206H, however, other alleles have been reported with atypical phenotypes. We report 14 cases presenting to a referral institution in South India over a 3-year period. The patients were clinically diagnosed based on foot abnormality or abnormal ectopic ossification and were screened for ACVR1. The genetic analysis of ACVR1 identified the recurrent allelic variant in 12 of 14 patients. One of the remaining patients had a previously reported allele c.1067G>A; p.G356D in the 9th exon and the second allele c.983G>A; p.G328E in the 8th exon of ACVR1. The most common recurrent allele c.617 G>A; p.R206H is also the most common in Indian patients with FOP., (© 2015 John Wiley & Sons Ltd/University College London.)

Soft tissue aneurysmal bone cyst is a rare entity, with about 20 cases reported in literature, only 3 of which are in patients over 40 years of age. We present a case of a 41 year old Latin American female who presented for evaluation of atraumatic chest pain with radiation to the left shoulder. Her initial workup was negative, including radiographic imaging of the chest and left shoulder. 4 months later, she presented to her orthopedic surgeon with a palpable mass and mild left shoulder pain. Radiographs acquired at that time demonstrated a 7.0 × 5.5 × 6.7 cm mass with rim calcification in the region of the upper triceps muscle. Subsequent CT imaging showed central areas of hypodensity and thin septations, a few of which were calcified. MR evaluation showed hemorrhagic cystic spaces with multiple fluid-fluid levels and enhancing septations. Surgical biopsy was performed and pathology was preliminarily interpreted as cystic myositis ossificans, however on final review the diagnosis of soft tissue aneurysmal bone cyst was made. The lesion was then surgically excised and no evidence of recurrence was seen on a 3 year post-op radiograph. Following description of our case, we conduct a literature review of the imaging characteristics, diagnosis, and treatment of soft tissue aneurysmal bone cyst.

Fibrodysplasia ossificans progressiva is the most severe and disabling disorder of ectopic ossification in humans. It is characterized by congenital skeletal abnormalities in association with extraskeletal widespread endochondral osteogenesis. Virtually all patients show the same mutation in the "Activin A type-I/activin-like kinase-2" receptor encoding gene. As a result of this discovery there have been significant advances in the knowledge of the cellular and molecular basis of the disease. Besides allowing a better understanding of ossification process, recent evidence indicates that the primary disturbance lies within basic mechanisms of cell differentiation that are key in several physiological pathways and in the genesis of diseases with a major impact on health. In this article we summarize these breakthroughs, with implications that go beyond the limits of this devastating disease to insinuate a new model of human pathophysiology., (Copyright © 2013 Elsevier España, S.L.U. All rights reserved.)