Intracellular protein messengers, called Smads are activated by the addition of a phosphate group, and form complexes that deliver BMP signaling to the cell nucleus.
The activated Smads regulate gene expression so the recruitment of stem cells are misdirected to differentiate into cartilage which is replaced by heterotopic bone.
A genetic mutation causes excessive BMP signaling
The mutation allows the receptor to become more active, especially when bounded by ligands such as BMPs or Activins.
There is a typical pattern of bone formation in FOP, in which heterotopic ossification (HO) is usually seen first in the dorsal, axial, cranial and proximal regions of the body and later in the ventral, appendicular, caudal, and distal regions.1 The episodic timing of HO formation and when ankylosis may occur varies among patients.2
FOP can have severe, disabling and life-shortening consequences,3 with the main causes of death being cardio-respiratory failure, pneumonia, and falls.3 Those consequences include:
Heterotopic bone formation in FOP is usually preceded by a flare-up, is episodic and unpredictable, with disability cumulative and permanent.