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Case Reports Indian Pediatrics 2003; 40:786-788 |
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Fibrodysplasia Ossificans Progressiva (FOP) |
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Luciana Brandão Paim Bernadete de Lourdes Liphaus Clovis Artur Almeida da Silva
Abstract: Fibrodysplasia ossificans progressiva (FOP) is a rare deforming disease, affecting the skeleton and is associated with progressive endochondral ossification of the striated muscles. Swelling of the soft parts is rare and can be the initial manifestation. We report three patients where initial swelling preceded the ossification. Key words: Endochondral ossification, FOP. Fibrodysplasia ossificans progressiva (FOP) is a connective tissue dominantly inherited autosomal disorder, in which defects in skeletal patterning are associated with progressive endochondral ossification of the large striated muscles(1-3). We present three patients with a diagnosis of FOP and initial swelling. Case Report Case 1: A 2-year-old female child presented with chronic facial swelling for 8 months followed by acute swelling and ossification in the scapula 3 years and 8 months later. Thumbs and big toes were hypoplastic along with hallux valgus malformation. Initial laboratory investigations were normal. Progressive skeletal radiographs showed ectopic ossification in neck, shoulders, sacral region, ankles and knees. The cutaneous and muscle biopsies showed juvenile fibro-matosis. Despite therapy (alendronate), the patient coursed with further evolutives ossifications (time of disease duration 1 year and 3 months). Case 2: A 9-year-old male child presented with trauma in left knee with claudication followed by acute swelling for three months and local ossification 3 years later. Hypoplasia of thumbs and big toes (Fig. 1), hallux valgus, complete sinodactyly and malformations of cervical vertebrae (C3-C6-C7) were observed. Laboratory Investigations were normal. Skeletal radiograph showed ectopic ossification in neck, shoulders, thoracic and abdominal walls, wrists, hips and legs. The cutaneous and muscle biopsies showed fibromatosis colli. Despite the therapy (colchicine, ethylenediaminetetraacetic acid -EDTA and methotrexate), the patient coursed with further evolutives ossifications (time of disease duration 3 years and 4 months).
Case 3: A 4-year-old female child presented with recurrent facial swelling for one year followed by swelling and ossification in the back. Hypoplasia of thumbs and big toes, hallux valgus, clinodactyly of all toes and fingers were observed. The laboratory investigations were normal, except for high levels of alkaline phosphatase. Progressive skeletal radiographies showed ectopic ossification in neck, thoracic walls, wrists, upper limbs and hips (Fig. 2). Despite the therapy (colchicine, EDTA and metho-trexate), the patient coursed with further ossifications until today, After three years, pulmonary function showed restrictive lung disease and the patient suffered permanent immobility after trauma and needed a wheel chair.
Discussion FOP is a disease of the mesodermal tissue, characterized by initial inflammation and subsequently coursing to proliferation of the fibrous tissue and formation of ectopic bone tissue. Its incidence is one case per two million inhabitants(4). The pre-bone lesion of FOP is indistinguishable histologically from the proliferative lesion of aggressive fibro-matosis(5), as in cases 1 and 2 that presented histological diagnoses of juvenile fibro-matosis and fibromatosis colli, respectively. The ectopic bone tissue formed is located in soft parts, mainly in the connective tissue of the striated musculature. The lesions begin in the paravertebral musculature and progress into the scapula, proximal portion of the arms, pelvis, jaw and skull(5,6). The ossification process can intensify in the presence of trauma, as occurred in cases 2 and 3(7). Initial swelling occurred in all our patients, and preceded the ossification. It is explained by the intense angiogenesis found in the precocious FOP lesion. Moriatis, et al.(8) reviewed 74 medical records and showed that acute swelling in the upper limbs occurred in all patients and acute swelling in the lower limbs occurred in 64% of the 74 patients. Chronic swelling in the upper limbs occurred in 12% and was not seen before the age of 12 years. Chronic swelling in the lower limbs occurred in 49% of the patients and was not seen before the age of 9 years(8). Symmetrical congenital malformations of the hands and feet occur in up to 90% of the cases and are considered essential for its diagnosis. The most frequent congenital abnormalities are hypoplasia of the thumbs, big toes and hallux valgus, these are due to shortening of the first phalange, as observed in all three patients. There are no specific laboratory alterations in FOP. Initially, the serum alkaline phosphatase can become elevated(5), as occurred in Case 3. Skeletal radiography is the preferential examination for its diagnosis and follow-up, by depicting the appearance of new ossification. FOP is a chronic disease with variable clinical course, characterized by periods of remission and exacerbation, since the ossified areas tend to remain stable(9). To date, there are no effective therapies to impede progression of the disease. However, several drugs have been suggested for the treatment of FOP, such as: retinoic acid(10), warfarin, and diphosphonate(11). Cortico-steroids can be useful for the acute process, but they do not prevent ectopic calcification. Some authors have demonstrated that the use of oral or intravenous diphosphonate(11-13), appears to be a therapeutic alternative to reduce ectopic calcifications. Despite therapy all the patients developed new ossification. Contributors: All the authors were involved in case management and writing the manuscript. Funding: None. Competiting interests: None stated.
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