Fibrodysplasia ossificans progressiva (FOP) is a debilitating, rare, autosomal dominant disorder of connective tissue characterized by malformed great toes and by progressive endochondral ossification of extra-skeletal sites (e.g., muscles, tendons, fascia) triggered by trauma, soft tissue injury, muscle fatigue, or viral infections. We present three children affected with FOP with this classic clinical presentation, the first reported cases in the Philippines, thus extending the range of classic FOP to new geographic and ethnic locations. Two of the affected children are siblings who have the common ACVR1 R206H mutation associated with classic FOP; this mutation was not found in their parents who are phenotypically unaffected, providing evidence of germline mosaicism in FOP. To our knowledge, this is the first family with genetic testing done showing presence of the classic mutation in affected siblings not seen in the unaffected parents.
Myositis Ossificans

PURPOSE: Neurogenic myositis ossificans (NMO) in patients with traumatic spinal cord or brain injuries can cause severe joint ankylosis or compromise neurovascularture. The purpose of this study was to evaluate the clinical and radiological outcomes of and review considerations relevant to surgical resection of NMO of the hip joint. MATERIALS AND METHODS: Six patients (9 hips) underwent periarticular NMO resection between 2015 and 2017. The medical records of these patients were retrospectively reviewed. Preoperative computed tomography including angiography was performed to determine osteoma location and size. Improvement in hip motion allowing sitting was considered the sole indicator of a successful surgery. The anterior approach was used in all patients. The ranges of motion (ROM) before and after surgery were compared. RESULTS: The mean time from accident to surgery was 3.6 years. Average ROM improved from 24.3°(flexion and extension) to 98.5°(flexion and extension) after surgery, and improvement was maintained at the last follow-up. No commom complications (e.g., deep infection, severe hematoma, deep vein thrombosis) occurred in any patient. Improvement in ROM in one hip in which surgical resection was performed 10 years after the accident was not satisfactory owing to the pathologic changes in the joint. CONCLUSION: Surgical excision of periarticular NMO of the hip joint can yield satisfactory results, provided that appropriate preoperative evaluation is performed. Early surgical intervention yields satisfactory results and may prevent the development of intra-articular pathology.
Angiography ; Ankylosis ; Brain Injuries ; Follow-Up Studies ; Hematoma ; Hip Joint ; Hip ; Humans ; Joints ; Medical Records ; Myositis Ossificans ; Myositis ; Osteoma ; Pathology ; Retrospective Studies ; Spinal Cord ; Veins

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease that is characterized by the formation of heterotopic bone tissues in soft tissues, such as skeletal muscle, ligament, and tendon. It is difficult to remove such heterotopic bones via internal medicine or invasive procedures. The identification of activin A receptor, type I (ACVR1)/ALK2 gene mutations associated with FOP has allowed the genetic diagnosis of FOP. The ACVR1/ALK2 gene encodes the ALK2 protein, which is a transmembrane kinase receptor in the transforming growth factor-β family. The relevant mutations activate intracellular signaling in vitro and induce heterotopic bone formation in vivo. Activin A is a potential ligand that activates mutant ALK2 but not wild-type ALK2. Various types of small chemical and biological inhibitors of ALK2 signaling have been developed to establish treatments for FOP. Some of these are in clinical trials in patients with FOP.
Activins ; Bone and Bones ; Diagnosis ; Humans ; In Vitro Techniques ; Internal Medicine ; Ligaments ; Muscle, Skeletal ; Myositis Ossificans* ; Osteogenesis ; Phosphotransferases ; Tendons ; Transforming Growth Factor beta

The two main forms of myositis ossificans are congenital and acquired. Either form is rare in the head and neck region. The acquired form is often due to trauma, with bullying as a fairly common cause. This report of myositis ossificans of the platysma in an 11-year-old female patient emphasizes the need for a high index of suspicion in unexplainable facial swellings in children and the benefit of modern investigative modalities in their management.
Bullying ; Child ; Female ; Head ; Humans ; Myositis Ossificans* ; Myositis* ; Neck ; Wounds and Injuries

Myositis ossificans circumscripta (MOC) is a kind of self-localized, benign and tumor-like lesions often seen in adults, with approximately 75% of cases caused by trauma. We reported a case of non-traumatic MOC occurred at the elbow joint in a 9-year old child and it has been excised by surgery. After 18 months follow-up, a favorable outcome has been achieved with the Broberg-Morrey score of 100. We suggest that surgical resection should be done as soon as the diagnosis is confirmed.
Arthralgia ; diagnostic imaging ; physiopathology ; Biopsy, Needle ; Child ; Elbow Joint ; diagnostic imaging ; pathology ; surgery ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging ; methods ; Male ; Myositis Ossificans ; diagnostic imaging ; surgery ; Orthopedic Procedures ; methods ; Pain Measurement ; Postoperative Care ; methods ; Range of Motion, Articular ; physiology ; Tomography, X-Ray Computed ; methods ; Treatment Outcome

Fibrodysplasia ossificans progressiva (FOP) syndrome is caused by mutation of the gene ACVR1, encoding a constitutive active bone morphogenetic protein type I receptor (also called ALK2) to induce heterotopic ossification in the patient. To genetically correct it, we attempted to generate the mutant ALK2-iPSCs (mALK2-iPSCs) from FOP-human dermal fibroblasts. However, the mALK2 leads to inhibitory pluripotency maintenance, or impaired clonogenic potential after single-cell dissociation as an inevitable step, which applies gene-correction tools to induced pluripotent stem cells (iPSCs). Thus, current iPSC-based gene therapy approach reveals a limitation that is not readily applicable to iPSCs with ALK2 mutation. Here we developed a simplified one-step procedure by simultaneously introducing reprogramming and gene-editing components into human fibroblasts derived from patient with FOP syndrome, and genetically treated it. The mixtures of reprogramming and gene-editing components are composed of reprogramming episomal vectors, CRISPR/Cas9-expressing vectors and single-stranded oligodeoxynucleotide harboring normal base to correct ALK2 c.617G>A. The one-step-mediated ALK2 gene-corrected iPSCs restored global gene expression pattern, as well as mineralization to the extent of normal iPSCs. This procedure not only helps save time, labor and costs but also opens up a new paradigm that is beyond the current application of gene-editing methodologies, which is hampered by inhibitory pluripotency-maintenance requirements, or vulnerability of single-cell-dissociated iPSCs.
Bone Morphogenetic Proteins ; Fibroblasts ; Gene Expression ; Genetic Therapy ; Humans ; Induced Pluripotent Stem Cells ; Miners ; Myositis Ossificans ; Ossification, Heterotopic

A calcification mass was incidentally found in the soft tissue of a patient who had a history of trauma to the extremity during examination. The patient had no symptom. The pathological analysis of the mass revealed it was an early-phase synovial sarcoma (SS). The diagnosis was made before the onset of symptoms and proper surgical intervention was performed. Therefore, in case of a <1 cm lesion clinically suspicious of myositis ossificans, SS should be taken into consideration as a possible diagnosis.
Diagnosis ; Extremities ; Femur ; Humans ; Myositis Ossificans ; Myositis ; Sarcoma, Synovial

Myositis ossificans (MO) is a benign condition of non-neoplastic heterotopic bone formation in the muscle or soft tissue. Trauma plays a role in the development of MO, thus, non-traumatic MO is very rare. Although MO may occur anywhere in the body, it is rarely seen in the lumbosacral paravertebral muscle (PVM). Herein, we report a case of non-traumatic MO in the lumbosacral PVM. A 42-year-old man with no history of trauma was referred to our hospital for pain in the low back, left buttock, and left thigh. On physical examination, a slightly tender, hard, and fixed mass was palpated in the left lumbosacral PVM. Computed tomography showed a calcified mass within the left lumbosacral PVM. Magnetic resonance imaging (MRI) showed heterogeneous high signal intensity in T1- and T2-weighted image, and no enhancement of the mass was found in the postcontrast T1-weighted MRI. The lack of typical imaging features required an open biopsy, and MO was confirmed. MO should be considered in the differential diagnosis when the imaging findings show a mass involving PVM. When it is difficult to distinguish MO from soft tissue or bone malignancy by radiology, it is necessary to perform a biopsy to confirm the diagnosis.
Biopsy ; Buttocks ; Diagnosis, Differential ; Magnetic Resonance Imaging ; Muscles ; Myositis ; Myositis Ossificans ; Osteogenesis ; Physical Examination ; Thigh

Myositis ossificans is a condition characterized by ossification within a muscle. It is a rare and unusual pathologic entity that has defied medical efforts to establish a definite etiology, pathogenesis, and satisfactory treatment of the disease. The condition predominantly affects the flexor muscles of the upper limbs and thighs, but rarely the head and neck area. A 53-year-old male patient visited our medical institution complaining of trismus, defined as limited mouth opening. The patient had a history of trauma to the facial bones and the computed tomography scans revealed calcification in the left temporalis muscle. The patient underwent surgical removal of the calcified mass with bilateral coronoidectomy under general anesthesia. Mouth opening at the end of post-operative 2 months was 28 mm. His oral intake of food was satisfactory. Myositis ossificans of the temporalis muscle is a very rare case. Satisfactory outcome was obtained by combining surgical excision of the affected muscle, coronoidectomy, and detachment of the insertion site of the ossified muscle.
Anesthesia, General ; Facial Bones ; Head ; Humans ; Male ; Mouth ; Muscles ; Myositis ; Myositis Ossificans ; Neck ; Thigh ; Trismus ; Upper Extremity

Humans ; Infant, Newborn ; Leg ; diagnostic imaging ; pathology ; Magnetic Field Therapy ; methods ; Male ; Myositis Ossificans ; diagnostic imaging ; pathology ; therapy ; Tomography, X-Ray Computed