Presentation

Fibrodysplasia ossificans progressiva (FOP) — formerly named “Myositis Ossificans Progressiva” — is a rare disorder of mesodermal tissue. FOP constitutes one of the most disabling congenital skeletal anomalies, characterized by progressive heterotopic ossification (HO) affecting soft tissues (muscles, fasciae, tendons, ligaments, aponeurosis). Its estimated prevalence is 1 per 2 million. FOP has an autosomal dominant inheritance pattern; however, de novo cases prevail. Most cases explain a heterozygous missense mutation in the bone morphogenetic protein (BMP) type I receptor, activin A receptor type I (ACVR1) gene on exon 6 (c.617G > A, p.R206H), which results in a gain of function. Based on clinical and molecular data, FOP can be classified as classic and non-classic [1,2,3].

We present a 3-year-old male with a confirmed diagnosis of classical FOP harboring the typical mutation. Since the newborn period, bilateral hallux valgus malformation was diagnosed. At 2 years, he presented heterotopic calcifications in the gluteal region. (Fig. 1a–c). Afterward, he developed enamel fragility, and additional HOs appeared, restricting his functional capacity and daily activities. No physical trauma was referred in relationship to HO occurrence.

Fig. 1
figure 1

a Bilateral hallux valgus deformity found in the patient. At birth b–d CT scan images: Axial image at pelvic level (b) and volumetric skeletal reconstructions (c, d), highlighting confluent bands of heterotopic ossifications in a male patient with FOP (yellow arrows)

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Discussion

FOP’s natural history includes minor congenital malformations of the great toes (hypoplasia, synostosis), leading to broad and short toes and hallux valgus deformity. Soft tissue local inflammation episodes develop from birth through adolescence and progress to HO. These “flare-ups” are frequently triggered by minor physical trauma or invasive medical interventions (injections or surgery); however, up to 40% are not related to trauma. The sternocleidomastoid muscle is usually the initial site of involvement; it can descend towards the shoulder girdle, the upper arms, the spine, and the pelvis [4]. The result is one or more ossification bridges between the limbs and the torso and between the thorax and the pelvis, leading to severe restriction of movement; the extent and severity of flare-ups are heterogeneous [1, 3]. Joint ankylosis may occur because of ossification of the nearby soft tissue structures and not the articular cartilage or synovial membrane involvement. Extra-skeletal involvement may include middle ear ossification leading to conductive deafness, demyelination, lymphedema, and venous thrombosis [5].

Plain radiographs and computed tomography may corroborate the diagnosis and assess its extent. Characteristic X-ray findings include ectopic calcifications within the soft tissues, bony bridges between the axial and appendicular skeleton that can be seen in advanced stages. In addition, magnetic resonance imaging plays a significant role in diagnosing early (preosseous stage) [4, 5].

No curative therapy is currently available, and corticosteroids and non-steroidal anti-inflammatory drugs are recommended for the acute phase of the flare-ups. Additionally, physical activity such as swimming is recommended to preserve joint mobility. Full recommendations have been published by The International Clinical Council on FOP (ICC) and Consultants [6]. The patient presented here developed HO events at an early age; even in the absence of physical trauma, these two features could mislead the diagnosis. Unawareness of this condition might lead to misdiagnosis, for example, juvenile idiopathic arthritis has been considered in some FOP patients [7]. Awareness needs to be spread among all medical specialties which potentially can face a case of FOP. Delayed diagnosis increases the risk of unnecessary interventions, such as biopsies or surgical procedures [1,2,3]. Education to healthcare professionals and patients’ families is imperative for early diagnosis and prevention of trauma of affected individuals.