Extra-skeletal osteosarcoma: a review.

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Abstract

[Indexed for MEDLINE] 7. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):191-205. doi: 10.1016/j.berh.2007.11.007. Fibrodysplasia ossificans progressiva. Kaplan FS(1), Le Merrer M, Glaser DL, Pignolo RJ, Goldsby RE, Kitterman JA, Groppe J, Shore EM. Author information: (1)Departments of Orthopedic Surgery & Medicine, The University of Pennsylvania School of Medicine, c/o Hospital of The University of Pennsylvania, Philadelphia, PA, USA. frederick.kaplan@uphs.upenn.edu 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. DOI: 10.1016/j.berh.2007.11.007 PMCID: PMC2424023