Prevalence of fibrodysplasia ossificans progressiva (FOP) in France: an estimate based on a record linkage of two national databases

Abstract

BackgroundFibrodysplasia ossificans progressiva (FOP) is a rare, severely disabling, and life-shortening genetic disorder that causes the formation of heterotopic bone within soft connective tissue. Previous studies found that the FOP prevalence was about one in every two million lives. The aim of this study is to estimate the FOP prevalence in France by probabilistic record-linkage of 2 national databases: 1) the PMSI (Programme de médicalisation des systèmes d’information), an administrative database that records all hospitalization activities in France and 2) CEMARA, a registry database developed by the French Centres of Reference for Rare Diseases.ResultsUsing a capture-recapture methodology to adjust the crude number of patients identified in both data sources, 89 FOP patients were identified, which results in a prevalence of 1.36 per million inhabitants (CI95% = [1.10; 1.68]). FOP patients’ mean age was 25 years, only 14.9% were above 40 years, and 53% of them were males. The first symptoms – beside toe malformations- occurred after birth for 97.3% of them. Mean age at identified symptoms was 7 years and above 18 years for only 6.9% of patients. Mean age at diagnosis was 10 years, and above 18 years for 14.9% of the patients. FOP patients were distributed across France.ConclusionsDespite the challenge of ascertaining patients with rare diseases, we report a much higher prevalence of FOP in France than in previous studies elsewhere. We suggest that efforts to identify patients and confirm the diagnosis of FOP should be reinforced and extended at both national and European level.

Longitudinal Evaluation of Pain, Flare‐Up, and Emotional Health in Fibrodysplasia Ossificans Progressiva: Analyses of the International FOP Registry

“…Fibrodysplasia ossificans progressiva (FOP) is an ultra‐rare (1:1,400,000 prevalence worldwide) and disabling inherited disorder that arises from missense mutations of the type I bone morphogenetic protein (BMP) receptor Activin A receptor type 1 (ACVR1) . To date, approximately 800 FOP cases have been documented.…”

“…F ibrodysplasia ossificans progressiva (FOP) is an ultra-rare (1:1,400,000 prevalence worldwide) and disabling inherited disorder that arises from missense mutations of the type I bone morphogenetic protein (BMP) receptor Activin A receptor type 1 (ACVR1). (1,2) To date, approximately 800 FOP cases have been documented. FOP is principally characterized by skeletal dysplasia and episodic heterotopic ossification (HO) of skeletal muscles, tendons, ligaments, and fascia.…”

Therapeutic advances for blocking heterotopic ossification in fibrodysplasia ossificans progressiva

“…Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition characterized by massive heterotopic ossification of the soft connective tissues, leading to progressive joint immobilization and disability . FOP affects approximately one in 1.3–2 million people worldwide and is typically diagnosed within the 1st decade of life . It is a progressive disease and is characterized by episodic flare‐ups in which patients develop painful, localized soft tissue inflammation, either spontaneously or in response to various triggers including trauma, injury, immunization or illness.…”

Molecular characterization of known and novel ACVR1 variants in phenotypes of aberrant ossification

“…Mutations in the bone morphogenetic protein (BMP) type I receptor, ACVR1, are known to cause the autosomal dominant connective tissue disorder, fibrodysplasia ossificans progressiva (FOP; MIM: 135100). Although rare, with a worldwide prevalence of ~1/2,000,000 (Connor & Evans, ), a more recent study estimates the prevalence in France as 1.36 per million inhabitants (Baujat et al, ). FOP is a severe condition with a young age of onset leading to debilitating ossifications starting in the first decade of life and decreased life expectancy (Pignolo, Shore, & Kaplan, ).…”