Fibrodysplasia ossificans progressiva complicated with post traumatic and infectious myositis ossificans in masseter: A case report.

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.

Challenges in the diagnosis of fibrodysplasia ossificans progressiva with the ACVR1 mutation (c.774G > C, p.R258S): a case report and review of literature.

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.

Myositis ossificans mimicking bone surface osteosarcoma: case report with literature review.

Myositis ossificans, a benign tumor composed of spindle cells and osteoblasts, can clinically and radiologically mimic osteosarcoma. While recognition and accurate diagnosis of myositis ossificans can be a challenge, this is critical as it may allow a conservative surgical approach to maximize functional outcomes. Herein, we present a patient with surface myositis ossificans confirmed genetically by the presence of COL1A1::USP6 gene fusion, along with a literature review. Due to the enhanced visualization of the bone matrix, computed tomography (CT) imaging may be a superior imaging modality to magnetic resonance (MR) imaging. Staged biopsies with samples obtained from the periphery and center of the lesions may allow pathologists to discern the zonal distribution histologically. Furthermore, immunohistochemistry fluorescence in situ hybridization and molecular testing can aid in the distinction of myositis ossificans from mimics. Because of their resemblance to other bone tumors, these cases of myositis ossificans highlight the importance of a multidisciplinary approach integrating clinical, radiologic, and pathologic analysis and involving serial imaging, sampling, and judicious use of ancillary immunohistochemical and molecular testing.

Successful preimplantation genetic testing for fibrodysplasia ossificans progressiva: a case report.

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.

Intersections of Fibrodysplasia Ossificans Progressiva and Traumatic Heterotopic Ossification.

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.

[Fibro-osseous pseudotumor of the digits: An exemple of USP6-related fibroblastic/myofibroblastic tumor]. / La pseudotumeur fibro-osseuse des doigts : une tumeur fibroblastique/myofibroblastique liée à USP6.

Fibro-osseous pseudotumor of the digits is a benign tumour closely related to myositis ossificans. It is a rare lesion seldom reported in the literature. We report the case of a 33-year-old woman with lancinating pain in the first phalanx of the second finger of the right hand, associated with inflammation. The histopathological examination of the surgical excision biopsy of the lesion revealed a spindle-shaped proliferation within a sclerosing, hyaline, and osteoid stroma. In our observation, immunohistochemistry and molecular biology are the main elements that helped to establish the diagnosis and eliminate the various differential diagnoses, despite a non-specific histopathological aspect.

Pay Attention to the Osteochondromas in Fibrodysplasia Ossificans Progressiva.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an extremely rare disease characterized by malformation of the bilateral great toes and progressive heterotopic ossification. The clinical features of FOP occur due to dysfunction of the bone morphogenetic protein (BMP) signaling pathway induced by the mutant activin A type I receptor/activin-like kinase-2 (ACVR1/ALK2) which contributes to the clinical features in FOP. Dysregulation of the BMP signaling pathway causes the development of osteochondroma. Poor awareness of the association between FOP and osteochondromas always results in misdiagnosis and unnecessary invasive operation. CASE PRESENTATION: In this study, we present a case of classical FOP involving osteochondroma. An 18-year-old male adolescent, born with deformity of bilateral big toes, complained multiple masses on his back for 1 year. The mass initially emerged with a tough texture and did not cause pain. It was misdiagnosed as an osteochondroma. After two surgeries, the masses became hard and spread around the entire back region. Meanwhile, extensive heterotopic ossification was observed around the back, neck, hip, knee, ribs, and mandible during follow-up. Osteochondromas were observed around the bilateral knees. No abnormalities were observed in the laboratory blood test results. Whole exome sequencing revealed missense mutation of ACVR1/ALK2 (c.617G > A; p.R206H) in the patient and confirmed the diagnosis of FOP. CONCLUSION: In summary, classical FOP always behaves as a bilateral deformity of the big toes, as well as progressive ectopic ossification and osteochondromas in the distal femur and proximal tibia. An understanding of the association between osteochondromas and FOP aids in diagnosis and avoids unnecessary invasive management in patients.

Disease aggravation following surgery in a rare patient suspected to Fibrodysplasia (Myositis) ossificans progressiva: a case report.

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.

[Recommendations for the healthcare of patients with FOP]. / Empfehlungen zur Versorgung von Patient:innen mit FOP.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is a very rare, severe genetic disorder triggered by a gain-of-function mutation in the ACVR1 gene that codes for the type I bone morphogenetic protein (BMP) receptor ACVR1 (activin A receptor-type 1), also known as ALK2 (activin receptor-like kinase-2). It leads to the onset and progression of heterotopic ossification (HO) in soft and connective tissue. HO is often preceded by episodes of soft tissue swelling or flare-ups. Flare-ups, characteristic of FOP, may be induced by trauma, infection, vaccination, or other medications, as well as surgical procedures or may occur spontaneously. As patients age, they develop severe mobility limitations due to progressive HO formation, including immobility, causing a shortened life expectancy. FOP's first characteristic clinical sign is the congenital malformation of one or both big toes with valgus axis deviation, which is present in almost all patients. To confirm the diagnosis, molecular genetic analysis of the ACVR1 gene is possible. AIM OF THE RECOMMENDATIONS: This white paper aims to provide an overview of the necessary prerequisites and conditions for the care of patients with FOP and positively contribute to patients with FOP by improving the overall availability of knowledge. To achieve this, relevant aspects of the care of the very rare disease FOP are presented, from the initial diagnosis to the care in regular care based on the authors' knowledge (German FOP network) and the international FOP Treatment Guidelines. The recommendations presented here are addressed to all actors and decision-makers in the health care system and are also intended to inform patients and the public.

Patient-specific PEEK implant for treatment of temporal myositis ossificans (five years follow-up): A case report.

Myositis ossificans of the temporalis muscle results in a cosmetic problem both before and after treatment because of the preoperative swelling and the postoperative defect respectively. The authors hypothesized that a patient-specific Polyether-ether ketone implant can be appropriate for immediate obliteration and reconstruction of such defect benefiting from the accuracy of CAD/CAM technology and computer-guided maxillofacial surgery. A Forty-year-old male patient with myositis ossificans affecting the left temporalis muscle was treated with a computer-guided surgical approach, a patient-specific implant was fabricated to obliterate the defect and avoid temporal hollowing using PEEK material. The functional and cosmetic results were satisfactory both immediately and at the 5-year follow-up, except that the skin over the implant was noticed to be stretched after 5 years. Hence, it can be concluded that virtual surgical planning and PEEK patient-specific implants are reliable in the immediate reconstruction of post-surgical temporal hollowing.

A rare femoral heterotopic bone formation in a 14th-19th century female skeleton from Constância (Portugal).

OBJECTIVE: This paper aims to: (1) document a rare femoral heterotopic ossification (HO), and (2) discuss its aetiology and impact on the individual's locomotion and daily living activities. MATERIALS: Adult female skeleton (SG.14-SK.7) from the village of Constância (Portugal), and dated from the 14th-19th centuries CE. METHODS: The biological profile and the macroscopic analysis of the bone changes were assessed using standardized methods. RESULTS: The macroscopic analysis revealed a large bony mass (8 cm length) located immediately inferior to the small trochanter of the right femur. The lesion exhibited a compact, tubular appearance located at the site of attachment of the pectineus muscle. No signs of bone fracture were observed. CONCLUSIONS: The morphology of the SG.14-SK.7 femoral lesion is compatible with a probable case of myositis ossificans traumatica (MOT), secondary to acute trauma of the pectineus muscle. The underlying trauma episode, such as random accidental and/or occupation-related injury, is unknown. However, it is highly possible that this self-limiting condition significantly impaired the individual's daily life and mobility. SIGNIFICANCE: Evidence of severe acute muscle trauma is a rare finding compared with HO secondary to bone trauma and other minor muscle injuries. Moreover, no cases of MOT affecting the pectineus muscle have been reported in the paleopathological literature to date. LIMITATIONS: Although unlikely, a case of neurogenic or burn-related HO cannot be completely disregarded. It was not possible to undertake radiography as part of this study. SUGGESTIONS FOR FURTHER RESEARCH: The use of imaging techniques to complement the paleopathological description is advised.

The Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ): A patient-reported, disease-specific measure.

OBJECTIVES: To assess the reliability and validity of age-specific versions of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ), developed to measure the impact of FOP on physical function and activities of daily living. METHODS: FOP-PFQ development included a literature review, two iterative phases of qualitative work involving individuals with FOP, and clinical expert review. The analysis used pooled FOP-PFQ data from an FOP natural history study (NCT02322255), a patient registry (NCT02745158), and phase II trials (NCT02190747; NCT02279095; NCT02979769). Item-level and factor analysis informed item retention and determined factor structure. Reliability was evaluated using Cronbach's alpha and intraclass correlation coefficients. Convergent validity was assessed by comparing scores with age, the Cumulative Analogue Joint Involvement Scale (CAJIS), the Patient-Reported Outcomes Measurement Information System Global Health Scale (PROMIS), and heterotopic ossification (HO) volume. Known-groups validity assessment used age, CAJIS, and HO volume. RESULTS: Factor analysis confirmed a two-factor solution: Mobility and Upper Extremity. Results reflected high internal consistency and were supportive of test-retest reliability; correlation coefficients >0.90 demonstrated FOP-PFQ scores were stable over a one- to three-week period. The majority of scores were moderately (r = 0.30-0.50) to highly (r ≥ 0.50) correlated with CAJIS and HO volume, supporting convergent validity. With the exception of some age-based and functional groups, FOP-PFQ scores were significantly worse in groups with more severe disease, demonstrating known-groups validity. CONCLUSION: The FOP-PFQ was demonstrated to be a reliable, valid measure that may be responsive to change in individuals with FOP, although some results were inconclusive for pediatric versions.

Myositis Ossificans with Aneurysmal Bone Cystic Changes at the Thoracic Paraspinal Region: A Case Report.

Myositis ossificans (MO) is a benign heterotopic bone formation in muscle or soft tissue. It is a self-limiting disease that is usually initiated by trauma and often occurs in the extremities of the body. Here we report a rare case of traumatic myositis ossificans caused by unusual trauma (extracorporeal shock wave therapy) at thoracic paraspinal muscles. After a needle biopsy, the lesion increased in size, and the patient's symptoms worsened. Malignant soft tissue tumors such as osteosarcoma should be differentiated, so excision of the mass was performed. The final diagnosis was MO with aneurysmal bone cystic change. This case is a very rare form of MO that showed an unusual cause, location, clinical course, and pathologic result on follow-up. This can be an instructive case for radiologists as it is a common disease entity with unusual manifestations.

"I Can't Take off My Shirt or Do My Own Hair"-A Qualitative Investigation of the Symptoms and Impact Experience of Children and Adolescents with Fibrodysplasia Ossificans Progressiva (FOP).

INTRODUCTION: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling, autosomal dominant, congenital disease characterized by progressive multi-focal heterotopic ossification (HO) of skeletal muscle, ligaments, tendons, and fascia. Past FOP studies have focused on the clinical aspects of the disease; therefore, there is a paucity of qualitative research on the patient experience. Our objective was to better understand the experience of children and adolescents living with FOP from their and their parents' perspectives. METHODS: We conducted a qualitative research study comprising in-depth, open-ended interviews with children and adolescents with FOP and their parents. Semi-structured interviews were conducted via phone call or Microsoft Teams with parent-child dyads (n = 11), adolescents (n = 6), and two clinicians. Children/adolescents and their parents were asked open-ended questions to elicit their daily experience of FOP. RESULTS: Concepts were organized into two major themes: symptoms of FOP and the impact of FOP on daily life. Symptoms of FOP reported by children/adolescents, parents, and clinicians were pain, swelling, redness, and stiffness. Functional impacts of flares and FOP in general included accommodations, mobility, activities of daily living, daily activities, and social activities. Impacts were attributed to the difficulties children and adolescents faced living with a disease that prohibited common activities. CONCLUSIONS: This research documented the experience of children and adolescents with FOP and its effects on their daily lives. It provides a conceptual model for further exploration of the symptoms and impacts important to children and adolescents with FOP and their parents. Children and adolescents and their parents offered novel insights into life with the disease that have not previously been discussed in published literature. Future studies should build upon our conceptual model to create a holistic view of the patient experience of FOP, to inform clinical practice, and the assessment of the patient experience in clinical trials for the disease.