Natural history of fibrodysplasia ossificans progressiva: cross-sectional analysis of annotated baseline phenotypes

• Published in: Orphanet journal of rare diseases 2019-05, Vol.14 (1), p.98-98, Article 98
• Main Authors: Pignolo, Robert J, Baujat, Geneviève, Brown, Matthew A, De Cunto, Carmen, Di Rocco, Maja, Hsiao, Edward C, Keen, Richard, Al Mukaddam, Mona, Sang, Kim-Hanh Le Quan, Wilson, Amy, White, Barbara, Grogan, Donna R, Kaplan, Frederick S
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Biomarkers; Birth defects; Blood; Child; Child, Preschool; Clinical trial endpoints; Clinical trials; Clinical Trials as Topic; Congenital defects; Cross-sectional analysis; Cross-Sectional Studies; Cytokines; Development and progression; Disease Progression; Dysplasia; Fascia; Female; Fibrodysplasia Ossificans Progressiva; Genetic aspects; Genetic disorders; Health aspects; Heterotopic ossification; Humans; Identification and classification; Information systems; Laboratories; Ligaments; Male; Medical imaging; Medical research; Middle Aged; Muscles; Mutation; Myositis ossificans; Myositis Ossificans - pathology; Natural history; Objectives; Ossification (ectopic); Ossification, Heterotopic - pathology; Patients; Phenotypes; Phosphatase; Product development; Proteins; Rare diseases; Regression analysis; Statistical analysis; Surveys and Questionnaires; Tendons; Tomography; Urine; Young Adult
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-019-1068-7

Fibrodysplasia Ossificans Progressiva (FOP; OMIM#135100) is an ultra-rare, severely disabling genetic disease characterized by congenital malformation of the great toes and progressive heterotopic ossification (HO) in muscles, tendons, ligaments, fascia, and aponeuroses often preceded by painful, recurrent soft tissue swelling (flare-ups). The formation of HO leads to progressive disability, severe functional limitations in joint mobility, and to a shortened life-span. In this prospective natural history study, we describe the baseline, cross-sectional disease phenotype of 114 individuals with FOP. All subjects underwent protocol-specified baseline assessments to determine their disease status. Cross-sectional analyses were performed using linear regression in which functional evaluations (Cumulative Analogue Joint Involvement Scale [CAJIS] and the FOP-Physical Function Questionnaire [FOP-PFQ]) and the burden of HO as measured by low-dose whole body CT (volume of HO and number of body regions with HO) were assessed. Findings from 114 subjects (age range 4 to 56 years) were evaluated. While subject age was significantly (p