Pay Attention to the Osteochondromas in Fibrodysplasia Ossificans Progressiva

Abstract

Background: Fibrodysplasia ossificans progressiva (FOP) is an extremely rare disease characterized by malformation of the bilateral great toes and progressive heterotopic ossification. The clinical features of FOP occur due to dysfunction of the bone morphogenetic protein (BMP) signaling pathway induced by the mutant activin A type I receptor/activin-like kinase-2 (ACVR1/ALK2) which contributes to the clinical features in FOP. Dysregulation of the BMP signaling pathway causes the development of osteochondroma. Poor awareness of the association between FOP and osteochondromas always results in misdiagnosis and unnecessary invasive operation.

Case presentation: In this study, we present a case of classical FOP involving osteochondroma. An 18-year-old male adolescent, born with deformity of bilateral big toes, complained multiple masses on his back for 1 year. The mass initially emerged with a tough texture and did not cause pain. It was misdiagnosed as an osteochondroma. After two surgeries, the masses became hard and spread around the entire back region. Meanwhile, extensive heterotopic ossification was observed around the back, neck, hip, knee, ribs, and mandible during follow-up. Osteochondromas were observed around the bilateral knees. No abnormalities were observed in the laboratory blood test results. Whole exome sequencing revealed missense mutation of ACVR1/ALK2 (c.617G > A; p.R206H) in the patient and confirmed the diagnosis of FOP.

Conclusion: In summary, classical FOP always behaves as a bilateral deformity of the big toes, as well as progressive ectopic ossification and osteochondromas in the distal femur and proximal tibia. An understanding of the association between osteochondromas and FOP aids in diagnosis and avoids unnecessary invasive management in patients.

Keywords: ACVR1/ALK2; Association; Bone Morphogenetic Protein; Fibrodysplasia Ossificans Progressiva; Osteochondromas.

FIGURE 1

Timeline of this disease.

FIGURE 2

(A) Multiple masses on the back (red arrow); (B) Bilateral valgus deformity of the great toes.

FIGURE 3

(A) Radiograph of the knee for consecutive 5 years demonstrated that the osteochondromas located at the bilateral distal femurs and proximal tibias kept constant in the morphology, volume and character. (B) Pathology of the mass revealed the osteochondromas with plenty of hyperplastic bone and cartilage.

FIGURE 4

Heterotopic ossifications. (A) The “armor‐like” ossification band on the back. (B) The heterotopic ossification of the right 8th rib and scoliosis to left. (C) and (D) The heterotopic ossification at bilateral hips and proximal humerus. (D‐H) The new formed heterotopic ossification at right thigh, bilateral knees, neck and the mandible after stopping taking the indomethacin. (I) The heterozygous mutation of the ACVR1 (c.617G>A; p.R206H) in this patient.