Fibrodysplasia ossificans progressiva

Frederick S. Kaplan, Martine Le Merrer, David L. Glaser, Robert J. Pignolo, Robert E. Goldsby, Joseph A. Kitterman, Jay Groppe, Eileen M. Shore

Research output: Contribution to journalReview articlepeer-review

210 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)191-205
Number of pages15
JournalBest Practice and Research: Clinical Rheumatology
Issue number1
StatePublished - Mar 2008


  • ACVR1
  • ALK2
  • BMP
  • bone morphogenetic protein
  • fibrodysplasia ossificans progressiva (FOP)
  • heterotopic ossification

ASJC Scopus subject areas

  • Rheumatology


Dive into the research topics of 'Fibrodysplasia ossificans progressiva'. Together they form a unique fingerprint.

Cite this