Fibrodysplasia Ossificans Progressiva - Recognising the Early features and Avoid Doing Harm

Abstract

Fibrodysplasia ossificans progressive (FOP) is an extremely rare noninflammatory disease that involves heterotrophic bone formation after tissue injury. Diagnosis of FOP is based on clinical suspicion for children presenting with bilateral hallux valgus and acute soft tissue swelling after trauma. Genetic analysis for mutation of the ACVR1 gene is considered a confirmatory test. We present 2 children with FOP that were diagnosed at seven years and twenty months of age respectively. The first patient presented with acute tissue swelling over the back and an incidental finding of hallux valgus. Genetic study revealed heterozygous c617G>A mutation in exon 4 of the ACVR1 gene suggestive of FOP. She had several relapses, and management pitfalls are highlighted. This first case alerted early diagnosis of FOP in a twentymonth-old boy with bilateral hallux valgus. Introduction Fibrodysplasia ossificans progressive is a rare noninflammatory disease involving genetic mutation of the ACVR1 gene, characterised by heterotopic bone formation and recurrent episodes of painful soft tissue swelling that arises spontaneously or is triggered by minor trauma.1 As with almost all rare diseases, there are various scientific and medical challenges in FOP diagnosis and management. As trauma is a stimulant event, biopsy and surgical interventions can cause devastating results at the site of ossification. Thus, it is essential to recognise early features of FOP including bilateral hallux valgus and recurrent soft tissue swelling and avoid tissue biopsy in suspected cases. We present 2 children with FOP and the management issues. Case 1 A 7-year-old girl presented with progressive left upper back swelling for three weeks after a minor contusion against the table corner. She had a history of mild bilateral conductive hearing impairment, otherwise unremarkable past health. Physical examination revealed mild scoliosis with diffuse swelling, erythema, and tenderness over the left paraspinal muscles. There was reduced movement over her back in all directions, especially over left lateral flexion, and reduced range of movement of both hips on internal and external rotation. Bilateral hallux valgus was noted. Autoimmune markers including anti-nuclear antibody, rheumatoid factor and anti-extractable nuclear antigen were negative. Magnetic resonance imaging (figure 1) revealed T2 hyper-intensity with soft tissue swelling around both scapulae, more severe over the left side. Bony structures appeared unremarkable. She was initially managed with regular physiotherapy for suspected muscle strain and treated with nonsteroidal anti-inflammatory drugs (NSAIDS) to control the inflammation. The treatment did not reduce the muscle discomfort, but stretching exercise aggravated the extent of muscle pain and subsequent “disease flared” over her right sternocleidomastoid muscle. The diagnosis of FOP was then considered. Genetic study revealed heterozygous c617G>A mutation in exon 4 of the ACVR1 gene. ACVR1 encodes for activin A receptor type I/ activin-like kinase 2, a bone morphogenetic protein type I receptor.2 Diagnosis of fibrodysplasia ossificans progressive was established. Since both parents did not have this mutation, it is likely a sporadic case. Subsequent disease flare-up involved the right thorax and right iliac crest, then left chest wall, followed by the left shoulder, then right arm, and her left thigh. Currently she is 17 years of age. During the flares, she had acute progressive swelling, tenderness, erythema with a limited range of movement over the affected site with or without a preceding trauma history. Short courses of high doses intravenous or oral corticosteroid were used for acute management of the flares. Despite that, progressive ossification could not be prevented. She currently has a marked fixation in the axial skeleton with severe kyphosis. Her spine is in 60-degree flexion, and her neck hyperextended at 10 degrees. She has severe micrognathia with receding chins. Her X-ray spine (figure 2a) revealed periosteal new bone over vertebral body L3-5. Her X-ray pelvis (figure 2b) showed bilateral acetabular dysplasia with multiple ossifications over the right hip joint and coxa magna. X-ray cervical spine (figure 2c) showed fusion of neural arches from C2 to C7. The hyperextension of the neck and severe micrognathia Address for Correspondance: Dr Natalie Wing Tung HO, Department of Paediatrics, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong SAR. Email: mandylamhiuching@gmail.com ©2021 Pediatric Oncall ARTICLE HISTORY Received 28 May 2021 Accepted 20 August 2021