Fibrodysplasia Ossificans Progressiva: A Challenging Diagnosis

Abstract

Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic condition characterized by extraskeletal bone formation. Most of the musculoskeletal characteristics of FOP are related to dysregulated chondrogenesis, with heterotopic ossification being the most typical feature. Activating mutations of activin receptor A type I (ACVR1), a bone morphogenetic protein (BMP) type I receptor, are responsible for the skeletal and nonskeletal features. The clinical phenotype is always consistent, with congenital bilateral hallux valgus malformation and early-onset heterotopic ossification occurring spontaneously or, more frequently, precipitated by trauma. Painful, recurrent soft-tissue swellings (flare-ups) precede localized heterotopic ossification that can occur at any location, typically affecting regions near the axial skeleton and later progressing to the appendicular bones. A diagnosis of FOP is suspected in a proband presenting with hallux valgus malformation, heterotopic ossification, and confirmed by the identification of a heterozygous pathogenic variant in the ACVR1/ALK2 gene. Avoiding unnecessary surgical procedures, prescribing prophylactic corticosteroids, preventing falls, and using protective headgear represent essential interventions for care management. Different classes of medications to contain acute inflammation flare-ups have been proposed, with high dose corticosteroids and nonsteroidal anti-inflammatory drugs usually utilized. Here, we report on two FOP patients, with typical clinical features summarizing the principal aspects of FOP, and we aim to provide comprehensive information outlining some unusual findings, possibly contributing to FOP’s definition and management.