Only three patients were suspected as having FOP by the pathologist on the basis of early cartilage and bone formation. Three additional biopsies showed mature heterotopic bone, but the patients were not diagnosed with FOP for unknown reasons. Radionuclide bone scanning with 99mTc-MDP was performed to determine active or residual foci of heterotopic ossification in 41 patients who had symptoms of FOP flare-ups including focal swelling, pain and/or decreased range of motion within the year prior to their clinic visit. 5-FU concentration Radioisotope uptake indicating mature heterotopic bone was

detected at remote sites of previously resolved flare-ups, as expected, in most individuals. However, if the patient was experiencing symptoms of an intercurrent flare-up of FOP at the time of the scan (focal pain, swelling) but heterotopic bone had not yet formed, no radionuclide uptake was detected. In Galunisertib order almost all cases of suspected clinical flare-up, heterotopic bone eventually formed. In only 3 among 50 cases with spontaneous onset did

the flare-up resolve spontaneously without forming clinically or radiographically evident heterotopic bone. Therefore, 99mTc-MDP bone scanning as performed in this FOP patient cohort was not a sensitive method for diagnosing early FOP flare-ups and was less accurate than clinical observation. Forty-one patients who had an FOP flare-up in the year prior to their initial evaluation had measurement for serum high-sensitivity C-reactive protein (hsCRP). Only two patients among the 41 had increased levels of hsCRP which were 12.0 and 27.3 mg/L respectively (normal: < 10 mg/L) [22]. China is the world's most populous nation with more than 1.3 billion people. Considering the extreme rarity of FOP and the predicted point prevalence of approximately 1:2,000,000, one would estimate the existence of at least 650 patients in China [2]. Until recently, only a few FOP patients

from China had been reported. Here we report 72 patients with confirmed FOP in China, the largest ethnically homogeneous population of FOP patients in the world. Together with the earlier case reports of six classic FOP patients [16], [17], [18], [19], [20] and [21], putatively 12% (78/650) of the population SPTBN5 of this disorder in China has been phenotypically and genotypically identified. Therefore, 88% of the expected FOP patients in China remain either undiagnosed or unknown to this medical team and are at risk of lifelong complications from misdiagnosis unless active educational programs are instituted to identify patients at risk. The early diagnosis of FOP can alert doctors and patients alike to avoid diagnostic misadventures [4] and [8]. Unfortunately, the misdiagnosis experience for FOP in China is similar to that reported elsewhere [4].