Thu0547 fibrodysplasia Ossificans Progressiva in Pediatric Rheumatology Practice: Large Series Experience of the Single Center

Abstract

BackgroundFibrodysplasia Ossificans Progressiva (FOP), also known as a “second skeleton disease” is extremely rare (1: 2000000) and disabling genetic disorder, caused by mutation of ACVR1 gene, a bone morphogenetic protein receptor. Among medical specialties there are no certain, capable to provide not only diagnostics, but also all medical maintenance (assessment and monitoring of extent of damages, the differentiated drug treatment, rehabilitation, contact with adjacent experts). It would be reasonable if the rheumatologist carried out a role of the main attending physician for the patient with FOP. It seems to be a lot of similarities between rheumatic diseases, especially spondyloarthritis (SpA) and FOP in the pathophysiology, clinical manifestation and the therapy approach.Objectives: to present the single-center experience of the FOP patients and to identify similar symptoms in FOP and rheumatic disease.MethodsThe analysis of the large series of patients with FOP, who observed in the rheumatologic clinic.ResultsOur single center experience includes 26 patients with FOP. All 26 patients (13 male and 13 female) had 3 basic FOP clinical manifestations. In 23 patients molecular-genetic tests were performed and typical mutation (Arginine 206) occurred in 22 cases and one had an extremely rare mutation (Glicine 328). 22 (85%) patients had common for FOP massive heterotopic ossifications. 3 of them had formed heterotopic ossification through the X-ray negative stage to visible changes. Among typical phenotypic stigmas were: great toe malformation; thumbs malformation; peripheral osteochondromas; cervical spine abnormalities. Majority of the cases presented some similarities to SpA manifestations: ankylosis of the apophysial joints and vertebral bodies mostly in cervical spine; X-ray/CT evidence of the sacroiliitis in all patients, who were examined (n=8). Because of severe body deformity or metal details after previous surgery intervention there were no possibility to perform MRI in most patients, but we confirm typical sacroiliitis with extended bone edema on MRI in 3 patients. Recurrent episodes of the large joints synoviitis were present in 5 patients. 4 patients demonstrated gradually formation of great toe ankylosis during the follow-up observation. The involution and decreasing of new FOP nodes associated with non-steroidal anti-inflammatory drug intake and/or glucocorticoids therapy were occurred in all patients.Clinical featuresMalefemaleTotal N of patientsSex ratio131326 (1:1)Age of initial manifestations (years) <1819 (35%) 1-96814 (54%) >10033 (11%)Great toe malformation131225 (96%)Thumbs malformation235 (19%)Cervical spine abnormalities12921 (81%)Peripheral osteochondromas8715 (58%)Massive heterotopic ossifications121022 (85%)CT/X-Ray/MRI picture of sacroiliitis2 (of 2)6 (of 6)8 of 8 (100%)ConclusionAppearance of the similarities in FOP and SpA manifestation and the therapy approach could identify FOP as a potential rheumatic disease. Clinical observation of FOP patients could provide the important inf...