Proximal Tibial Osteochondromas in Patients with Fibrodysplasia Ossificans Progressiva

Abstract

Proximal tibial osteochondromas are a common phenotypic feature of fibrodysplasia ossificans progressiva, a finding that expands the recognized consequences of recurrent activating mutations in activin A receptor type I to include not only congenital skeletal malformations and heterotopic skeletogenesis but also benign osteochondral neoplasms or orthotopic lesions of skeletal modeling. The present study provides insight into the genetic basis of osteochondroma formation in patients with fibrodysplasia ossificans progressiva and possibly into that of more common conditions in which these lesions occur.

Insights from a rare genetic disorder of extra-skeletal bone formation, fibrodysplasia ossificans progressiva (FOP)

“…Congenital malformation of the great toes ( Figure 1) is the earliest phenotypic feature of FOP [9][10][11]. This is the most recognizable skeletal feature of FOP, although other subtle skeletal changes (such as cervical spine fusions, short/broad femoral necks, and osteochondromas) also commonly occur [12][13][14].…”

Cell biology of osteochondromas: Bone morphogenic protein signalling and heparan sulphates

“…Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder resulting in progressive heterotopic ossification of skeletal muscle and soft connective tissue [7]. Dysregulation of the BMP signalling pathway is involved in the disease.…”

“…Dysregulation of the BMP signalling pathway is involved in the disease. FOP is known to be caused by a missense mutation in the ACVR1 gene resulting in the activation of BMP type I receptor ALK2 [7,33]. Skeletal similarities between FOP and MHE include short broad femoral necks and metaphyseal widening.…”

“…Skeletal similarities between FOP and MHE include short broad femoral necks and metaphyseal widening. Like MHE, FOP patients have a high incidence of osteochondroma formation, especially on the proximal tibia [7]. These similarities may suggest that the two conditions may share overlapping pathophysiological mechanisms [7].…”

“…Like MHE, FOP patients have a high incidence of osteochondroma formation, especially on the proximal tibia [7]. These similarities may suggest that the two conditions may share overlapping pathophysiological mechanisms [7]. Therefore, it is sensible to suggest that the BMP signalling pathway may play a role in MHE and osteochondroma formation.…”