Pediatric Fibrodysplasia Ossificans Progressiva (Myositis Ossificans)

Updated: Oct 26, 2015
  • Author: Robert J Pignolo, MD, PhD; Chief Editor: Lawrence K Jung, MD  more...
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Overview

Background

Fibrodysplasia ossificans progressiva (FOP) is a rare and disabling genetic condition characterized by congenital malformations of the great toes and progressive heterotopic ossification (HO) in specific anatomic patterns. [1]

Extensive heterotopic ossification on the back of Extensive heterotopic ossification on the back of a patient with fibrodysplasia ossificans progressiva.
Characteristic malformed great toes and hallux val Characteristic malformed great toes and hallux valgus.

Most cases arise as a result of a spontaneous new mutation. Genetic transmission is autosomal dominant and can be inherited from either parent. Fibrodysplasia ossificans progressiva is the most catastrophic disorder of heterotopic ossification in humans. Flare-ups are episodic; immobility is cumulative.

Myositis ossificans is a misnomer, although the term myositis ossificans circumscripta continues to be used to describe nonhereditary forms of heterotopic ossification.

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Pathophysiology

Progressive postnatal heterotopic ossification in fibrodysplasia ossificans progressiva usually appears within the first decade of life as spontaneous or injury-induced exacerbations. The lesions are characterized by painful swellings in soft connective tissue, including tendons, ligaments, fascia, and skeletal muscle. [2]

Mounting evidence from all levels of investigation suggests involvement of the inflammatory component of the immune system in fibrodysplasia ossificans progressiva. The presence of macrophages, lymphocytes and mast cells in early fibrodysplasia ossificans progressiva lesions, macrophage and lymphocyte-associated death of skeletal muscle, flare-ups following viral infections, the intermittent timing of flare-ups, and the beneficial response of early flare-ups to corticosteroids support involvement of the innate immune system in the pathogenesis of fibrodysplasia ossificans progressiva lesions.

The genetic cause of fibrodysplasia ossificans progressiva was identified as a recurrent missense mutation in the GS activation domain of activin receptor Ia/activinlike kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor, in all individuals with classic fibrodysplasia ossificans progressiva. [3, 4] Recently, additional mutations have been identified in the GS-domain and kinase domain of ACVR1 in individuals with atypical forms of fibrodysplasia ossificans progressiva. [5, 6, 7] Noggin mutations have been reported but cannot be substantiated and are erroneous.

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Epidemiology

Frequency

International

Fibrodysplasia ossificans progressiva is rare with a worldwide prevalence of approximately 1 case in 2 million individuals.

Race

No ethnic, racial, or geographic predisposition is noted.

Sex

No sex predisposition is noted.

Age

Most children with fibrodysplasia ossificans progressiva develop episodic, painful inflammatory soft tissue swellings (or flare-ups) during the first decade of life. [1, 8]

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