Fibrodysplasia ossificans progressiva

The origins of fibrodysplasia ossificans progressiva in human history are unknown, but the condition has been well described since Freke's account in 1740. Important contributions by physicians and scientists in the past 250 yr have converged on the remarkable skeleton of Harry Eastlack at the Mutter Museum of the College of Physicians in Philadelphia.     

Fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva (FOP), a rare and disabling genetic condition of congenital skeletal malformations and progressive heterotopic ossification (HO), is the most catastrophic disorder of HO in humans. Episodic disease flare-ups are precipitated by soft tissue injury, and immobility is cumulative. Recently, a recurrent mutation in activin receptor IA/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor, was reported in all sporadic and familial cases of classic FOP, making this one of the most highly specific disease-causing mutations in the human genome. The discovery of the FOP gene establishes a critical milestone in understanding FOP, reveals a highly conserved target for drug development in the transforming growth factor (TGF)-beta/BMP signalling pathway, and compels therapeutic approaches for the development of small molecule signal transduction inhibitors for ACVR1/ALK2. Present management involves early diagnosis, assiduous avoidance of iatrogenic harm, and symptomatic amelioration of painful flare-ups. Effective therapies for FOP, and possibly for other common conditions of HO, may potentially be based on future interventions that block ACVR1/ALK2 signalling.     

Fibrodysplasia ossificans progressiva: case report

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by widespread soft tissue ossification and congenital stigmata of the extremities. We report the case of a 33-year-old woman with clinical and radiological features of FOP. She was born with bilateral hallux valgus and at the age of 10 presented swelling and ossification of the left scapula. During the course of the disease numerous crises were observed. In this patient authors noticed FOP exacerbation after a surgical operation.     

Fibrodysplasia ossificans progressiva without characteristic skeletal anomalies

Fibrodysplasia ossificans progressiva (FOP) is a rare but extremely disabling genetic disease of the skeletal system. This disease is characterized by progression of heterotopic ossification within skeletal muscles, ligaments and tendons. Most patients with FOP are misdiagnosed early in life before the appearance of heterotopic ossification and undergo diagnostic procedures such as biopsy that can cause lifelong disability. Almost all of the patients have some peculiar congenital anomalies, including short great toes, hallux valgus, short thumbs and hypoplasia of digital phalanges. These congenital defects support the diagnosis of FOP, but are not constantly observed in the totality of patients. If necessary, genetic studies can be performed to confirm the diagnosis. Once diagnosed, patients should be advised in order to avoid unnecessary traumas, surgical procedures, biopsies, intramuscular injections and vaccinations. Here, we describe a patient with FOP without characteristic congenital skeletal anomalies.     

Fibrodysplasia ossificans progressiva and progressive osseous heteroplasia

Heterotopic ossification (HO) as a primary clinical finding is uncommon, but it occurs in two human genetic disorders: fibrodysplasia ossific, ans progressiva (FOP) and progressive osseous heteroplasia (POH). In these disorders, the progression and stages of the ectopic bone formation appear normal, but disregulation of cell differentiation leads to improper induction of bone formation—in other words, normal bone forms in the wrong place at the wrong time. Cases of POH were initially recognized following misdiagnosis as FOP. However, POH can be distinguished from FOP by several criteria: the presence of cutaneous ossification, the absence of congenital malformations of the skeleton, the absence of inflammatory tumor-like swellings, the asymmetric mosaic distribution of lesions, the absence of predictable regional patterns of HO, and the predominance of intramembranous rather than endochondral ossification. Both FOP and POH are rare conditions, with most cases apparently the result of a de novo (spontaneous) mutation: however, when inherited, both are transmitted through an autosomal-dominant inheritance pattern. Although FOP can be inherited from either a mother or a father, POH is only inheried paternally. Consistent with this parental inheritance pattern, POH patients carry inactivating mutations of the GNAS gene, a gene that is regulated through genomic imprinting and allele-specific gene expression. The genetic cause of FOP remains undetermined. A combination of clinical and genetic evaluations can identify FOP and POH, two distinct disorders of extensive HO.     

Fibrodysplasia ossificans progressiva: report of two cases

Fibrodysplasia Ossificans Progressiva (FOP) is a rare hereditary connective tissue disease, genetically inherited as an autosomal dominant trait with complete penetrance but variable expressivity. Onset is typically in childhood and progressive involvement of the spine and proximal extremities leads to immobility and articular dysfunction. We present two cases with the typical features of FOP and a review of the pathogenesis, clinical manifestations and treatment options of this rare disease.     

Fibrodysplasia ossificans progressiva in a Malian boy of Bamako

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare hereditary connective tissue disorder characterized by congenital malformation of the great toes and by progressive heterotopic ossification of striated muscles and soft tissues. We report a case of FOP in a Malian boy and review the clinical and radiographic manifestations of this disorder. The body TDM showed ossifications and calcifications in the muscles of the large rhomboid, the erector muscles of the rachis and the trapezius muscles.Radiography of the dorsolumbar rachis showed paravertebral soft tissue calcification adjacent to intact lumbar vertebrae. The diagnosis is based on clinical and radiological findings and demonstration of skeletal malformations. The differential diagnosis of this rare condition from other muscle and joint disease is discussed. There is no effective prevention or treatment. There is a need for a wider knowledge of this condition.     

进行性骨化性纤维发育不良三例并文献复习

目的：探讨进行性骨化性纤维发育不良的临床特征、诊断、鉴别诊断及治疗对策。方法：分析3例进行性骨化性纤维发育不良的临床、X线特 和病情加重原因，并复习相关文献。结果：3例患儿，男性1例，女性2例，年龄2－11岁，平均5．3岁，起病年龄生后10d-2岁，平均1．7岁，病程2－11年，平均5．3年，均有反复软组织内团块状肿物，局部疼痛，肿物自行消失，或遗留不规则骨性肿块，进行性中轴和／或四肢关节外组织骨性僵硬，X线检查，颈部、躯干、四肢软组织内不规则骨化影，颈部软组织最易受累，其次为腰背、胸部、四肢、髋、臀、腹部。双侧拇、趾骨短缩，形态不规则，2例骨化范围广泛，均在多次静脉注射，病变组织活检后，骨化进展加快，结论：进行性骨化性纤维发育不良是一种少见的先天性结缔组织疾病，病因未明，治疗措施，避免导致异常骨化加重的刺激，如创伤，骨折，活检和肌肉注射等，拇趾畸形有助于早期诊断，尤在异位骨化发生前，易误诊为骨肉瘤，多发性骨疣 、幼年类风湿关节炎、皮肌炎、纤维织化性肌炎等。     

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

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. The diagnosis is difficult and there is no effective treatment for FOP and the approximate life expectancy is 4 decades.Patient concerns:A 22-year-old male patient who had suffered from pain and movement limitations for 14 years. At the early stage of disease, the child underwent an operation on both thighs with a diagnosis of myophagism. He had serious stiffness and multiple bony masses with the characteristic bilateral hallux valgus deformity and microdactyly.Diagnoses:The patient was diagnosed with FOP by the help of characteristic great toe malformations and widespread heterotopic ossification throughout the body. Deoxyribonucleic acid sequencing demonstrated that the patient had a de novo heterozygous mutation (c.617G>A; p.R206H) in activin A receptor/activin-like kinase 2.Interventions:We administered a co-therapy of glucocorticoids, NSAIDs to relieve pain, and montelukast for 2 months. Bisphosphonate (5 mg, intravenous) was used once.Outcomes:At the follow-up 12 months later, the patient still felt low back pain sometimes and need take NSAIDs three times a week.Lessons:Clinicians and radiologists should realize the characteristic features of FOP and early diagnosis can prevent additional invasive harm to the patient.     

Fibrodysplasia ossificants progressiva.

Two cases of fibrodysplasia ossificans progressiva are reported. Both patients were females and had suffered from the disease since birth. The characteristic anomalies of great toes and thumbs associated with multiple ectopic ossifications of the connective tissue are described. Fasciae, tendons, ligaments, and joint capsules of the proximal parts of the extremities and the dorsal aspect of the trunk were involved. The muscle atrophy was probably a secondary phenomenon.     

Myositis ossificans progressiva

The case of a 19-year-old female patient with myositis ossificans progressiva is reported. This disease is a rare hereditary disorder with a dominant autosomal genotype. The patient had typical ossifications of the humeral and dorsal muscles, as well as of those of the left thigh and upper arm, and also an ankylosis of the left hip. There were typical deformations of the cervical vertebrae and of the skeleton of the hands and feet. Laboratory tests showed alkaline phosphatase to be greatly increased. ECG revealed a bifascicular bundle-branch block, and a high-grade restrictive ventilation disorder was shown up by pulmonary function test. When the stability of the genetic material was investigated, DNA synthesis was found to be normal, DNA repair was slightly accelerated, and the sister chromatid exchange rate following stimulation with mitomycin C was higher than in controls.     

The fibrodysplasia ossificans progressiva lesion

Clinically, the lesions in fibrodysplasia ossificans progressiva (FOP) follow spontaneous or injury-induced exacerbations and are characterized by painful swellings in soft connective tissue that progress to form mature heterotopic bone. Heterotopic ossification (HO) progresses in characteristic anatomic and temporal patterns, and the location of HO dictates the severity of functional consequences. The histological stages of lesion formation are well described and include, in order of progression: perivascular lymphocytic infiltration (stage 1A), lymphocytic migration into affected muscle and myonecrosis (stage 1B), early reactive fibroproliferation (stage 1C), intense fibroproliferation, neovascularity, and angiogenesis (stage 2A), cartilage formation (stage 2B), and endochondral bone formation (stage 2C). Possible mechanisms for FOP lesion formation, including the origin of bone-forming cells, are discussed.     

A case report of myositis ossificans progressiva complicated by femoral nerve compression treated with radiotherapy

SIR, We present a female who was noted to have abnormal toesfrom birth. At age 19 yr she developed a lump below her jawand lumps in both shoulders and the left breast with progressivemusculoskeletal stiffness and pain. A biopsy of one lesion revealedfibrosis, focal muscle destruction and inflammation. Myositisossificans progressiva was then diagnosed. She presented aged 34 yr with a 5-week history of right thighpain, fixed flexion deformity of the thigh causing inability     

The phenotype of fibrodysplasia ossificans progressiva

The phenotype of fibrodysplasia ossificans progressiva (FOP) includes two defining features: congenital malformation of the great toes and progressive heterotopic ossification in characteristic anatomic patterns. Additional common features include proximal medial tibial osteochondromas, orthotopic fusions of the posterior elements of the cervical spine, broad short femoral necks, and conductive hearing loss. The FOP phenotype supports that the primary molecular pathology involves the bone morphogenetic protein (BMP)-signaling pathway directly or a BMP-interacting pathway.