Journal
GENETICS IN MEDICINE
Volume 24, Issue 12, Pages 2422-2433Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.gim.2022.08.013
Keywords
Fibrodysplasia ossificans progressiva; Natural history study
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Funding
- Ipsen
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This study presents the first prospective, international, natural history study of fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder. The results demonstrate the debilitating effects and progressive nature of FOP, with the most significant progression observed during childhood and early adulthood.
Purpose: We report the first prospective, international, natural history study of the ultra-rare genetic disorder fibrodysplasia ossificans progressiva (FOP). FOP is characterized by painful, recurrent flare-ups, and disabling, cumulative heterotopic ossification (HO) in soft tissues. Methods: Individuals aged <= 65 years with classical FOP (ACVR1(R206H) variant) were assessed at baseline and over 36 months. Results: In total, 114 individuals participated; 33 completed the study (mean follow up: 26.8 months). Median age was 15.0 (range: 4-56) years; 54.4% were male. During the study, 82 (71.9%) individuals reported 229 flare-ups (upper back: 17.9%, hip: 14.8%, shoulder: 10.9%). After 84 days, 14 of 52 (26.9%) imaged flare-ups had new HO at the flare-up site (mean new HO volume: 28.8 x 10(3) mm(3)). Mean baseline low-dose whole-body computed tomography (excluding head) HO volume was 314.4 x 10(3) mm(3); lowest at 2 to <8 years (68.8 x 10(3) mm(3)) and increasing by age (25-65 years: 575.2 x 10(3) mm(3)). The mean annualized volume of new HO was 23.6 x 10(3) mm(3)/year; highest at 8 to <15 and 15 to <25 years (21.9 x 10(3) and 41.5 x 10(3) mm(3)/year, respectively) and lowest at 25 to 65 years (4.6 x 10(3) mm(3)/year). Conclusion: Results from individuals receiving standard care for up to 3 years in this natural history study show the debilitating effect and progressive nature of FOP cross-sectionally and longitudinally, with greatest progression during childhood and early adulthood. (c) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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