Abstract
We present two cases of Fibrodysplasia Ossificans Progressiva (FOP), a rare genetic disorder characterized by heterotopic ossification and malformation of the great toes. The heterotopic ossification is preceded by episodic soft tissue swellings (flare-ups) and results in restricted mobility of the joints. Its rarity, especially in the maxillofacial region, often results in misdiagnosis. Episodes of painful new bone results from any surgical attempt to excise the heterotopic bone. It is imperative for clinicians to be aware of this condition in order to make early diagnosis and to prevent iatrogenic harm to these patients through unnecessary diagnostic or surgical procedures. In addition, with this information, clinicians can take the necessary precautions in the prevention of oral disease and maintenance of meticulous oral hygiene.
Highlights
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Fibrodysplasia Ossificans Progressive (FOP) is a rare genetic disorder.
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It is characterized by heterotopic ossification and malformation of the great toes.
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We present two cases of Fibrodysplasia Ossificans Progressiva.
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Early and correct diagnosis of FOP helps in preventing iatrogenic harm.
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The rarity of FOP justifies publication of the two present cases to increase awareness amongst clinicians.
1
Introduction
Fibrodysplasia ossificans progressive (FOP) is an extremely rare, heritable disorder of connective tissue metamorphosis, characterized by congenital malformation of the great toes and progressive postnatal heterotopic ossification of skeletal muscles, tendons, ligaments, aponeurosis and fascia [ ]. The heterotopic ossification is preceded by soft tissue swellings with heat and pain, colloquially referred to as “flare-ups”. FOP occurs due to a recurrent heterozygous activating genetic mutation in the intracellular glycine-serine-rich (GS) domain of Activin receptor type 1A/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenic protein (BMP) type 1 receptor signalling endochondral ossification4, 5, 6. This bone morphogenic protein receptor mutation results in the activation of the BMP Smad 1/5/8 signalling pathway, with resultant induction of extraskeletal bone formation in FOP patients . It usually occurs de novo, but there are cases described with autosomal dominant inheritance.
The incidence of FOP is reported to be 1 in 2 million. Its rarity often results in misdiagnosis and unnecessary treatment. We report on two cases of FOP that occurred in 6-year-old girls. These cases are of particular interest in that correct and early diagnosis resulted in urgent treatment under strict guidelines in the one and avoided counterproductive surgery in the other.
2
Case presentation
2.1
Case 1
A 6 1 / 2 -year-old girl presented to the Chris Hani Baragwanath Academic Hospital (CHBAH) Maxillofacial and Oral Surgery unit with a chief complaint of progressive stiffening of her joints and subsequent severe restriction in mouth opening of two years’ duration ( Fig. 1 ).
She had a history of restricted movements of her arms and neck. She had swellings involving the neck, shoulders and over the back, which began when she was four years of age. She consulted a regional hospital, which then referred her to our institution with a differential diagnosis of myositis ossificans. The patient did not present with any medical or dental history of significance other than the history of an acute soft tissue flare-ups that were treated at another tertiary hospital. Details of this treatment was not documented. She reported that the flare-ups started spontaneously on the back of her neck and extended over the head. Since then she noticed the bony exostosis and limited joint movement, especially on the shoulders, temporomandibular joints and elbows.
2.1.1
Clinical examination
Patient presented with a weight of 20 kg, height of 122 cm and head circumference of 55 cm. Patient presented with a prominent occiput, and restricted mouth opening (5 mm) due to stiffness of the temporomandibular joints ( Fig. 1 ). A pectus excavatum deformity was noted on the chest. Multiple irregular bony hard lumps were noted on the chest and at the back in the posterior thorax ( Figs. 1 and 2 ).
The fingers appeared long with bilateral clinodactyly of the 5th digits. The halluces were laterally deviated and short ( Fig. 3 ). Severely restricted range of motion (ROM) in the elbow joints, temporomandibular joints, left knee joint and limited flexion of the cervical spine were noted. The cardiovascular, abdomen, female genitalia and skin examinations were normal.
2.1.2
Special investigation
Lateral skull and cervical spine radiograph revealed bony bridging bone formation (heterotopic ossification) between occipital and spinous processes of Axis and 3rd cervical vertebra ( Fig. 4 ). Interspinous ligament ossification spanning between Axis and cervicothoracic junction was also noted.
Lower limb radiographs displayed ossification on the femoral and tibial condyles ( Fig. 5 ). Antero-posterior (AP) chest radiograph showed linear ossification along the lateral chest wall surrounding both scapulae ( Fig. 6 ). Also visible on this view were ossifications around the right elbow joint.
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