Prevalence of fibrodysplasia ossificans progressiva (FOP) in the United States: estimate from three treatment centers and a patient organization

Abstract

Background Fibrodysplasia ossificans progressiva (FOP), an ultra-rare, progressive, and permanently disabling disorder of extraskeletal ossification, is characterized by episodic and painful flare-ups and irreversible heterotopic ossification in muscles, tendons, and ligaments. Prevalence estimates have been hindered by the rarity of FOP and the heterogeneity of disease presentation. This study aimed to provide a baseline prevalence of FOP in the United States, based on contact with one of 3 leading treatment centers for FOP (University of Pennsylvania, Mayo Clinic, or University of California San Francisco), the International Fibrodysplasia Ossificans Progressiva Association (IFOPA) membership list, or the IFOPA FOP Registry through July 22, 2020. Results Patient records were reviewed, collected, and deduplicated using first and last name initials, sex, state, and year of birth. A Kaplan–Meier survival curve was applied to each individual patient to estimate the probability that he or she was still alive, and a probability-weighted net prevalence estimate was calculated. After deduplication, 373 unique patients were identified in the United States, 294 of whom who were not listed as deceased in any list. The average time since last contact for 284 patients was 1.5 years. Based on the application of the survival probability, it is estimated that 279 of these patients were alive on the prevalence date (22 July 2020). An adjusted prevalence of 0.88 per million US residents was calculated using either an average survival rate estimate of 98.4% or a conservative survival rate estimate of 92.3% (based on the Kaplan–Meier survival curve from a previous study) and the US Census 2020 estimate of 329,992,681 on prevalence day. Conclusions This study suggests that the prevalence of FOP is higher than the often-cited value of 0.5 per million. Even so, because inclusion in this study was contingent upon treatment by the authors, IFOPA membership with confirmed clinical diagnosis, and the FOP Registry, the prevalence of FOP in the US may be higher than that identified here. Thus, it is imperative that efforts be made to identify and provide expert care for patients with this ultra-rare, significantly debilitating disease.

Protocol paper: a multi-center, double-blinded, randomized, 6-month, placebo-controlled study followed by 12-month open label extension to evaluate the safety and efficacy of Saracatinib in Fibrodysplasia Ossificans Progressiva (STOPFOP)

“…Firstly, rare diseases by their very definition have a limited number of patients, often distributed across the globe. The low prevalence of FOP, estimated to be 1 in 1 million [ 4 , 5 , 26 ], and that only a subset of these patients will be both willing to participate and eligible for participation, the STOPFOP project opted for a RCT design combined with open label extension and comparison to a natural history data. This strategy allows for increased statistical power with a lower number of patients.…”

“…An especially devastating rare disease is Fibrodysplasia Ossificans Progressiva (FOP): this genetic, disease is characterized by severe heterotopic ossifications (HO) in muscle, tendons and ligaments and has a prevalence of about 1 in 1 million [ 4 , 5 ]. HO is often, but not always, preceded by inflammatory symptoms (e.g.…”

Extensive progressive heterotopic ossification post-Covid-19 in a man

“…Genetic HO has a significant clinical severity compared to non-genetic causes and includes fibrodysplasia ossificans progressiva (FOP), previously known as myositis ossificans progressive. It is an extremely rare genetic skeletal disorder with an apparent prevalence that varied substantially from 0.65 per million in the United States to 1.4 in Sweden [7] , [8] . It is caused by heterozygous mutation in the ACVR1/ALK2 gene (OMIM: #135100) encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic protein (BMP) type I receptor [9] , [10] .…”

Limitations of Jaw Movement in Fibrodysplasia Ossificans Progressiva: A Review

“…Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder with a prevalence of 1 in 2 million people ( 1 , 2 ). It is characterized by congenital malformation of the great toes (bilateral hallux valgus) and by progressive heterotopic ossification (HO) of the skeletal muscles, fascia, tendons and ligaments ( 3 , 4 ).…”