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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibrodysplasia (myositis) ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by symmetrical congenital malformations of the blastemal anlage of the hands and feet and by progressive heterotopic chondrogenesis and ossification of the soft connective tissues. There is neither an established pathogenesis nor an effective treatment for this disabling disorder. We reevaluated the published data on the natural history of FOP and discovered an array of developmental gradients (characteristic patterns of disease expression) similar to developmental anomalies induced by pleiotropic mutations of the decapentaplegic (dpp) locus in Drosophila melanogaster. The protein encoded by the dpp locus is a member of the transforming growth factor-beta (TGF-beta) family of molecules. It shares 75% sequence homology with the c-terminal region of two recently cloned human bone morphogenetic proteins (BMP-2A, BMP-2B), also members of the TGF-beta family. The striking sequence identity across so large an evolutionary distance suggests that the BMP-2 genes in man and the dpp gene in the fly may be derived from a common ancestral gene. BMP is the only molecule discovered thus far that is capable of inducing endochondral ossification in vivo. Expression of endochondral bone formation is the basis for limb formation in embryogenesis, longitudinal bone growth in postnatal life, and local bone regeneration (fracture healing) following injury. We believe that FOP is a genetic disorder characterized by a disturbed developmental expression of this endochondral program and may represent a mutation resulting in a dominant gain of function. The developmental similarities between decapentaplegic in the fly and FOP in man suggest a useful model for the study of FOP. The use of such a model might be especially fruitful in suggesting a molecular basis for FOP.
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PMID:Fibrodysplasia ossificans progressiva: a clue from the fly? 211 91

Fibrodysplasia (myositis) ossificans progressiva (FOP) is a rare autosomal dominant disorder in which 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. We report a 5 year-old female case with FOP.
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PMID:Fibrodysplasia ossificans progressiva. 800 96

Patients with fibrodysplasia (myositis) ossificans progressiva (FOP) (n = 28) were studied for up to 24 years. All had characteristic short big toes potentially recognizable at birth; there were radiographic changes in the toes, thumbs, cervical spine and metaphyses of the long bones, including exostoses. Ossification in the large skeletal muscles began from birth to 16 years (mean age 4.6 years) initially in 25 patients in the neck and upper spinal muscles, and later around the hips, major joints and jaw. The rate and extent of disability was unrelated to the time of onset. There was no evidence that any form of treatment produced consistent benefit. Despite the unique combination of skeletal abnormalities and ectopic ossification, the first diagnosis in patients with FOP was often wrong and usually delayed after ectopic ossification began (mean 2.7 years, range 0-14). Except where presentation was unusual, such as progressive stiffness, this delay was mainly due to failure to recognize the significance of the abnormal toes. The most frequent erroneous histological diagnoses were soft tissue sarcoma or fibromatosis. This series emphasizes the usually incorrect initial diagnosis, the misinterpretation of the histology, the unpredictable prognosis and the failure of current treatment. Despite its extreme rarity, there is a need for wider knowledge of this condition both to avoid clinical errors and to stimulate research.
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PMID:Fibrodysplasia (myositis) ossificans progressiva: clinicopathological features and natural history. 875 48

Fibrodysplasia (myositis) ossificans progressiva (FOP) is an extremely rare inherited disorder in which progressive ossification of major striated muscles, often following injury, is associated with abnormal skeletal patterning. Altered expression of bone morphogenetic proteins may be a contributory cause. To examine this hypothesis, we compared the patterns of expression of bone morphogenetic proteins (BMPs) mRNAs from lymphoblastoid cell lines from two small multigenerational families with autosomal dominant transmission of FOP. Although affected members of both families showed the characteristic phenotype of FOP, one family was more severely affected than the other. Expression of mRNAs for BMP-1, 2, 3, 5, and 6 mRNAs were not detected within the more severely affected family, but BMP-4 mRNA was expressed in affected but not unaffected members of this family. The results of linkage exclusion analysis using a highly polymorphic microsatellite marker near the BMP-4 gene were consistent with linkage of FOP and BMP-4 in this family. Within the less severely affected family, affected and unaffected members showed similar levels of mRNA expression of BMPs 1, 2, 4, and 5, and linkage of FOP to the BMP-4 gene was excluded. It is concluded that clinical, radiographic, and biochemical data in these two families with FOP establish clinical and molecular heterogeneity and also suggest the possibility of genetic heterogeneity.
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PMID:Phenotypic and molecular heterogeneity in fibrodysplasia ossificans progressiva. 1044 61

Fibrodysplasia (or Myositis) Ossificans Progressiva (FOP) is a rare genetic disease with variable expression, characterized by the association of congenital anomalies of the toes and fingers and progressive appearance of ectopic bone within the skeletal muscles, often following a trauma or an infection. FOP initially affects the nape and thoracic paravertebral muscles. With age, there is a progression of ossifications to other muscular groups following a proximodistal and cranio-caudal extension. Patients develop a restrictive respiratory insufficiency with atelectasis. The diagnosis of FOP is clinical and does not require biopsy. Circumscribed post-traumatic ossifying myositis is the most important differential diagnosis. It is characterized by the appearance of painful ossifications, in young adults, following a trauma and is limited to one localisation. The conservative treatment of FOP remains unsatisfactory. Surgical removal of osteomas to restore joint mobility leads to the development of additional heterotopic ossifications. Each surgical attempt brings about a quasi-inevitable recurrence. Anaesthesia of patients with FOP is difficult because of spinal rigidity and ankylosis of the jaw. Surgery is indicated only with a focused indication to correct an invalidating deformity.
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PMID:Fibrodysplasia ossificans progressiva: diagnosis and surgical management. 2166 23