Fibrodysplasia Ossificans Progressiva: Early Diagnosis Is Critical yet Challenging

Figure 3. Chest magnetic resonance imaging performed 1 month after the initial presentation as a baseline study for FOP follow-up (axial T2-weighted image). Soft tissue swelling with abnormal signal (hyperintense on T2-weighted and short tau inversion recovery [STIR] images, hypointense on T1-weighted images) in the left paravertebral muscles and the muscles and fascial planes in the lateral and posterior aspect of the left chest wall. These findings are in keeping with FOP, although there was no pathologic calcification on gradient sequences. A mass after a fall from a chair 3 weeks earlier. Ultrasound scanning findings were consistent with intramuscular trauma. Seven days later, with another ultrasound scan, a postero-lateral thoracic mass extending to the posterior neck was shown. Infection or malignancy was suspected, and biopsy of the lesion was considered. However, a radiologist recognized that the history of remote minor back trauma was discordant with persistent swelling and tenderness and reviewed all imaging. Foot radiographs taken at 2 years of age (Figure 1) and clinical findings (Figure 2) were pathognomonic for fibrodysplasia ossificans progressiva (FOP). FOP is a rare (prevalence, 0.61 per million) but progressive, debilitating disease with no effective treatment. FOP can be diagnosed on the basis of two classic clinical findings: congenital skeletal malformation of the great toes and progressive heterotopic ossification. Shortening of the first metatarsal and hallux valgus occurs in 75% of patients. The development of rapidly growing masses, usually in the neck or paravertebral region (Figure 3), is caused by fibroblastic proliferation and ossification of subcutaneous fat, fascia, muscles, tendons, aponeuroses, and ligaments. The soft tissue masses can grow spontaneously, but trauma can accelerate the growth and calcification. FOP is poorly recognized and often diagnosed late (in our case, a 3-year delay) or misdiagnosed (approximately 90%), often as tumor-like lesions, which may result in unnecessary and harmful biopsies, surgery (two-thirds), or both that exacerbate the condition, resulting in permanent harm in >50% of cases. Therefore, awareness of the clinical features of FOP by all physicians, but particularly pediatricians, is essential for timely diagnosis. We suggest that for any child with malformed great toes, especially those associated with soft tissue swellings, FOP should be suspected. Then genetic testing can be conducted and iatrogenic harm can be avoided and perhaps disease progression slowed. n