Fibrodysplasia ossificans progressiva (FOP): A disorder of osteochondrogenesis

Frederick S Kaplan¹, Mona Al Mukaddam², Alexandra Stanley³, O Will Towler⁴, Eileen M Shore⁵

Affiliations

¹ Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: Frederick.Kaplan@pennmedicine.upenn.edu.
² Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: Mona.AlMukaddam@pennmedicine.upenn.edu.
³ Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: astanley@health.ucsd.edu.
⁴ Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: otowler@pennmedicine.upenn.edu.
⁵ Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: shore@pennmedicine.upenn.edu.

PMID: 32730934
PMCID: PMC7502483
DOI: 10.1016/j.bone.2020.115539

Review

Fibrodysplasia ossificans progressiva (FOP): A disorder of osteochondrogenesis

Frederick S Kaplan et al. Bone. 2020 Nov.

. 2020 Nov:140:115539.

doi: 10.1016/j.bone.2020.115539. Epub 2020 Jul 27.

Authors

Frederick S Kaplan¹, Mona Al Mukaddam², Alexandra Stanley³, O Will Towler⁴, Eileen M Shore⁵

Affiliations

¹ Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: Frederick.Kaplan@pennmedicine.upenn.edu.
² Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: Mona.AlMukaddam@pennmedicine.upenn.edu.
³ Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: astanley@health.ucsd.edu.
⁴ Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: otowler@pennmedicine.upenn.edu.
⁵ Department of Orthopaedic Surgery, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA; The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: shore@pennmedicine.upenn.edu.

PMID: 32730934
PMCID: PMC7502483
DOI: 10.1016/j.bone.2020.115539

Abstract

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder of extraskeletal bone formation, but could appropriately be viewed as a seminal disorder of osteochondrogenesis. Many, if not most, of the musculoskeletal features of FOP are related to dysregulated chondrogenesis including abnormal articular cartilage formation, abnormal diarthrodial joint specification, growth plate dysplasia, osteochondroma formation, heterotopic endochondral ossification (HEO), and precocious arthropathy. In FOP, causative activating mutations of Activin receptor A type I (ACVR1), a bone morphogenetic protein (BMP) type I receptor, are responsible for the osteochondrodysplasia that impacts developmental phenotypes as well as postnatal features of this illustrative disorder. Here, we highlight the myriad developmental and postnatal effects on osteochondrogenesis that emanate directly from mutant ACVR1 and dysregulated bone morphogenetic protein (BMP) signaling in FOP.

Keywords: ACVR1; Arthropathy; Bone morphogenetic protein signaling pathway; Degenerative joint disease; Fibrodysplasia ossificans progressiva; Growth plate; Heterotopic ossification; Osteochondrodysplasia; Osteochondrogenesis; Osteochondroma.

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Figures

**Figure 1.**
A hypothetical schema of FOP includes the broad developmental features of joint dysplasia, growth plate dysplasia and osteochondroma formation as well as the predominant post-natal feature of FOP: heterotopic endochondral ossification (HEO).

See this image and copyright information in PMC

References

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Fibrodysplasia ossificans progressiva (FOP): A disorder of osteochondrogenesis

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Fibrodysplasia ossificans progressiva (FOP): A disorder of osteochondrogenesis

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