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...

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Bibliographic Details
Published in:Best practice & research. Clinical rheumatology 2008-03, Vol.22 (1), p.191-205
Main Authors: Kaplan, Frederick S., MD, Le Merrer, Martine, MD, PhD, Glaser, David L., MD, Pignolo, Robert J., MD, PhD, Goldsby, Robert E., MD, Kitterman, Joseph A., MD, Groppe, Jay, PhD, Shore, Eileen M., PhD
Format: Article
Language:English
Subjects:
Activin Receptors, Type I - genetics
ACVR1
ALK2
Animals
BMP
bone morphogenetic protein
Bone Morphogenetic Protein Receptors, Type I - genetics
Bone Morphogenetic Proteins - genetics
Disease Models, Animal
fibrodysplasia ossificans progressiva (FOP)
heterotopic ossification
Humans
Mutation
Myositis Ossificans - diagnosis
Myositis Ossificans - diagnostic imaging
Myositis Ossificans - genetics
Myositis Ossificans - physiopathology
Myositis Ossificans - therapy
Ossification, Heterotopic
Radiography
Rheumatology
Smad Proteins - genetics
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Description
Summary: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)-β/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.
ISSN:1521-6942
1532-1770
DOI:10.1016/j.berh.2007.11.007