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Ectopic pseudojoints in fibrodysplasia ossificans progressiva
Robert J Pignolo1, Mona Al Mukaddam2,3,4, Stephen Broski5
1Department of Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, United States.
JBMR Plus
|August 4, 2025
Summary
Pseudoarthroses, or false joints, are reported at ectopic sites in patients with Fibrodysplasia ossificans progressiva (FOP). This finding suggests the BMP pathway
Area of Science:
- Genetics
- Orthopedics
- Biochemistry
Background:
- Pseudoarthroses typically occur in the normotopic skeleton following fracture complications.
- Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder causing progressive heterotopic ossification (HO) and congenital skeletal abnormalities.
- Ectopic pseudojoint formation has not been previously reported.
Observation:
- Six patients with FOP developed ectopic pseudojoints.
- These formations occurred after flare-ups and HO in soft tissues around the knee, hip, and forearm.
- This represents the first known instance of ectopic pseudojoints in humans.
Findings:
- Dysregulated BMP pathway signaling, mediated by mutant ACVR1, is implicated in both HO and ectopic pseudojoint formation in FOP.
- Ectopic pseudojoints can arise from de novo musculoskeletal elements.
- FOP is uniquely associated with ectopic pseudojoint formation.
Implications:
- This research expands the understanding of FOP's skeletal manifestations beyond HO.
- It highlights the role of the BMP pathway in complex ectopic tissue formation.
- Further research into ACVR1 signaling may reveal novel therapeutic targets for FOP and related conditions.
Keywords:
ACVR1BMP signalingfibrodysplasia ossificans progressivaheterotopic ossificationpseudoarthrosispseudojointMore Related Videos
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