Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by painful, recurrent episodes of soft tissue swelling (flare-ups) that result in abnormal bone formation in muscles, tendons, and ligaments. Flare-ups begin early in life and may occur spontaneously or after soft tissue trauma, vaccinations, or influenza infections. Recurrent flare-ups progressively restrict movement by locking joints leading to cumulative loss of function and disability. This 3-year, non-interventional, two-part, natural history study is designed to gain insight into total body HO, FOP disease progression, the impact of FOP on subjects' physical functioning, and clinical features and biomarkers that may be useful in the diagnosis and monitoring of disease progression. This natural history study will also provide important information to inform the design of subsequent interventional trials.

This is a multi-center, natural history, non-interventional, longitudinal study in subjects with classic FOP. A thorough baseline examination will be performed to determine the current status of disease in each subject. In Part A, two imaging modalities assessed total body HO at baseline, and the optimal method (low-dose whole body CT scan [excluding head]) will be employed in Part B for the balance of the study. Progression will be assessed at annual in-clinic visits (ie, at Months 12, 24, and 36) at which time the procedures conducted at the baseline visit will be repeated. In addition, site personnel will telephone subjects midway between the annual visits (ie, at Months 6, 18, and 30).

During the 36-month follow-up period, at least one new flare-up (with a maximum of one per year) will be carefully studied. An in-clinic visit will be performed within 14 days following the subject's identification of his/her flare-up. Additional visits at Day 42 and Day 84 (after the initial flare-up clinic visit) will be performed. An additional future visit may be scheduled after Day 84 at the discretion of the Principal Investigator (PI) for prolonged flare-ups. However, subjects with an eligible flare-up may elect to participate in an ongoing Clementia interventional study rather than continue in this natural history study.

Inclusion Criteria:

- Subjects clinically diagnosed with classical FOP with documented R206H mutation or believed to carry the R206H mutation

Exclusion Criteria:

- Participation in an interventional clinical research study within the 4 weeks prior to enrollment

Individuals with classic FOP (R206H mutation).