TY - JOUR
T1 - The natural history of fibrodysplasia ossificans progressiva
T2 - A prospective, global 36-month study
AU - Pignolo, Robert J.
AU - Baujat, Geneviève
AU - Brown, Matthew A.
AU - De Cunto, Carmen
AU - Hsiao, Edward C.
AU - Keen, Richard
AU - Al Mukaddam, Mona
AU - Le Quan Sang, Kim Hanh
AU - Wilson, Amy
AU - Marino, Rose
AU - Strahs, Andrew
AU - Kaplan, Frederick S.
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/12
Y1 - 2022/12
N2 - 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 (ACVR1R206H 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 × 103 mm3). Mean baseline low-dose whole-body computed tomography (excluding head) HO volume was 314.4 × 103 mm3; lowest at 2 to <8 years (68.8 × 103 mm3) and increasing by age (25-65 years: 575.2 × 103 mm3). The mean annualized volume of new HO was 23.6 × 103 mm3/year; highest at 8 to <15 and 15 to <25 years (21.9 × 103 and 41.5 × 103 mm3/year, respectively) and lowest at 25 to 65 years (4.6 × 103 mm3/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.
AB - 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 (ACVR1R206H 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 × 103 mm3). Mean baseline low-dose whole-body computed tomography (excluding head) HO volume was 314.4 × 103 mm3; lowest at 2 to <8 years (68.8 × 103 mm3) and increasing by age (25-65 years: 575.2 × 103 mm3). The mean annualized volume of new HO was 23.6 × 103 mm3/year; highest at 8 to <15 and 15 to <25 years (21.9 × 103 and 41.5 × 103 mm3/year, respectively) and lowest at 25 to 65 years (4.6 × 103 mm3/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.
KW - Fibrodysplasia ossificans progressiva
KW - Natural history study
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U2 - 10.1016/j.gim.2022.08.013
DO - 10.1016/j.gim.2022.08.013
M3 - Article
C2 - 36152026
AN - SCOPUS:85138833026
SN - 1098-3600
VL - 24
SP - 2422
EP - 2433
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 12
ER -