Improving the Diagnosis of Fibrodysplasia Ossificans Progressiva

Abstract

Fibrodysplasia ossificans progressiva (FOP) is a distinctive but often-overlooked disorder, owing to its extreme rarity and insidious presentation. However, the signs of classic FOP are evident at birth, and the disease clinically manifests typically within the first decade of life. The characteristic and invariably early sign of FOP is congenital malformation of the great toes (Figure 1). 1 Pignolo R.J. Wang H. Kaplan F.S. Fibrodysplasia ossificans progressiva (FOP): a segmental progeroid syndrome. Front Endocrinol (Lausanne). 2020; 10: 908 Crossref PubMed Scopus (12) Google Scholar , 2 Pignolo R.J. Shore E.M. Kaplan F.S. Fibrodysplasia ossificans progressiva: clinical and genetic aspects. Orphanet J Rare Dis. 2011; 6: 80 Crossref PubMed Scopus (159) Google Scholar , 3 National Organization for Rare Disorders [homepage on the Internet]. 2020https://rarediseases.org/rare-diseases/fibrodysplasia-ossificans-progressiva/ Google Scholar In 50% of cases, the thumbs are similarly affected. Other findings at birth may include a broad femoral neck and bony malformation of the cervical spine. 4 Meyers C. Lisiecki J. Miller S. Levin A. Fayad L. Ding C. et al. Heterotopic ossification: a comprehensive review. JBMR Plus. 2019; 3: e10172 Crossref PubMed Scopus (95) Google Scholar , 5 The International Clinical Council on FOP (ICC) and Consultants [homepage on the Internet]. 2019https://d3n8a8pro7vhmx.cloudfront.net/ifopa/pages/212/attachments/original/1559059247/FOP_TREATMENT_GUIDELINES_June_2019.pdf Google Scholar , 6 International Fibrodysplasia Ossificans Progressiva Association (IFOPA) [homepage on the Internet]. 2020www.ifopa.org/what_is_fop Google Scholar Heterotopic ossification, the abnormal growth of bone in extraskeletal tissues, typically is not present at birth, although areas of soft-tissue swelling may be evident in neonates. Infants and children with FOP may present to pediatric orthopedic surgeons with progressive “bunions” or malformed great toes. However, it is rare that the disease is recognized at this stage. In most cases, unfortunately, the diagnosis of FOP is not made until affected persons have consulted several physicians and the associated deformity and disability are undeniable. 7 Kapan F. Xu M. Glaser D.L. Collins F. Connor M. Kitterman J. et al. Early diagnosis of fibrodysplasia ossificans progressiva. Pediatrics. 2008; 121: e1295-e1300 Crossref PubMed Scopus (113) Google Scholar It is estimated that 3500-4000 people worldwide have FOP, although the disorder has been diagnosed in only about 900 people. 3 National Organization for Rare Disorders [homepage on the Internet]. 2020https://rarediseases.org/rare-diseases/fibrodysplasia-ossificans-progressiva/ Google Scholar Although there are currently no approved treatments for FOP, early recognition and diagnosis is important to prevent unnecessary trauma, such as intramuscular vaccination or surgery, that may induce disease flares.