fibrodysplasia ossificans progressiva ( fop ) is a rare autosomal dominant genetic disorder and characterized by postnatal progressive heterotopic ossification of the connective tissue .
there are difficulties in diagnosing fop , thus delayed or misdiagnosis and mismanagement is common .
3d printers have now become widely available and inexpensive , and can be used to rapidly produce life - size models based on ct scans of an individual patient .
the availability of patient specific , accurate and detailed models of complex acetabular fractures can aid planning of surgical management on a patient specific basis .
we present the diagnosis and surgical management of a 9-year old indonesian girl with fop .
total excision of occipito - cervico - lumbar and paravertebral ossification and also exostoses at bilateral shoulder was done . at three years
follow up , she had local recurrence with similar range of movement of the shoulder and cervical spine .
it is difficult to diagnose and manage fop , therefore delayed or misdiagnosis and also inappropriate management is common .
fibrodysplasia ossificans progressiva ( fop ) , once called myositis ossificans progressiva , is a rare autosomal disorder that involves connective tissue .
one of the famous case of fop is harry eastlack ( 1933 - 1973 ) , who died because of pneumonia and fully ossified body , his lips were the only body part that could be used properly .
ectopic ossification is preceded by a soft tissue enlargement that may spontaneously resolve or gradually form an ectopic bone . delayed or missed
we report a rare case of fop arising at occipito - cervical spine , paravertebrae , and bilateral shoulders focusing on diagnostic procedure and surgical management .
a 9-year - old girl presented to our orthopaedic clinic , with main complaint of a mass which was getting bigger on her upper back .
the initial mass size was around 1 cm in diameter ( like a marble ) located just below the tip of both scapulae .
it was accompanied by difficulty in moving both shoulders and neck since 4 years . because of these complains , her family tried various traditional medicines without improvement .
six months prior to admission , she fell down on her back , and since then the masses grew progressively .
she was brought to a district hospital in other province and then referred to our hospital to get more appropriate treatment .
there was no history of similar disease in her family . on physical examination , general condition was good and no abnormality was found in other organ .
we found multiple bony prominences measuring about 2 cm in diameter at paravertebral region from cervical to lumbar and posterior thoracic wall .
they made bone bridges starting from inferior occipital bone to cervical spine and extending to paravertebral lumbar region .
the shoulder , cervical , and thoracal spine ranges of movement were limited ( fig 1 ) .
there were multiple bony prominence measuring 2 cm in diameter at the back from cervical to lumbar and posterior thoracic region ( arrows ) , they made bony bridges from inferior occipital bone , cervical spine , extending to paravertebral lumbar region .
( b ) slight valgus deformity of right great toe ( arrow ) radiograph of the cervical spine showed new bone formation starting from occipital bone , cervical , until upper thoracal spine .
chest and shoulder radiographs also showed new bone formation at both humerus bridging to the tip of scapulae , with subluxation of both humeral head superiorly .
the radiologist saw it as mustiple exostoses ( osteochondroma lesion ) with the differential diagnosis progressive myositis ossificans .
hla - b27 was negative , it was investigated since we also thought ankylosing spondylitis as a differential diagnosis . the 3d computerized tomography ( ct ) reconstruction revealed multifocal ossification on soft tissue including right pectoral muscle , bilateral latissimus dorsi , and left longisimus thoracis muscle .
magnetic resonance imaging ( mri ) showed similar result with ct scan and no other abnormality detected at the spine .
radiograph of the cervical spine lateral view showed bone formation starting from occiput , cervical , and upper thoracic spine ( arrows ) .
( b ) chest and shoulder radiographs also showed bone formation at the bilateral humerus bridging to the tip of scapula ( arrows ) .
( c ) ct reconstruction revealed multifocal ossification which supported radiographic finding , paravertebral bony bridge ( arrow head ) , bony bridges from bilateral humerus to tip of scapula ( arrows ) because of the problem was multiple exostoses and stiffness , total excision of occipito - cervico - lumbar and paravertebral ossification and also exostoses at bilateral shoulder was done .
histopathological findings showed tissue consisting of cartilaginous component , irregular underlying bony trabeculae , and bone marrow between trabeculae .
after review of all patient s data in one of the clinicopathological conference , we concluded that it was fibrodysplasia ossificans progressiva ( fop ) .
four months after surgery local recurrences were detected , which was confirmed with radiograph ( fig 4 ) . at three years follow up , she had similar signs and symptoms as before surgery .
( a)histopathology showed formation of endochondral ossification ( arrow ) ( h&e , 100x ) .
( b ) skeletal muscle and formation of endochondral ossification ( arrow ) ( h&e , 100x ) . ( c )
formation of endochondral ossification ( arrow head ) , bone trabeculae and marrow ( arrow ) ( h&e , 100x ) .
( a ) clinical picture 4 months after surgery , local recurrences were detected ( arrow ) .
( b ) cervical radiograph 4 months after surgery , there was local recurrence of bony bridge from occiput , cervical , and upper thoracic spine ( arrow ) .
( c ) thoracic radiograph 4 months after surgery , there was recurrence of bony bridge from bilateral humerus to the tip of scapula ( arrow head ) .
fop is an autosomal dominant disorder and has a variable expression that is the most catastrophic disorder of heterotopic ossification in humans .
primary genetic defects in fop are currently unknown . events which may precipitate formation of lesion are trauma , invasive medical procedure , muscle fatigue , influenza like infection , and immunization .
however , it is still unclear how clinical events which initiate the formation of lesion ultimately lead to extraskeletal ossification .
a study in japan involving 19 fop subjects has successfully identified gene mutation that could induce ectopic bone formation in fop .
fop lesion is usually triggered by soft tissue injury , predominantly in muscle , causing release of inflammatory cytokines and migratory factors .
potential soluble mediators include prostaglandins ( pgs ) , smad1 and smad5 , stromal cell derived factor 1 , and bmp-4 .
pge2 has an anabolic effect on bone marrow stromal cells and may enhance osteoblastic differentiation in - vitro , presumably through the recruitment of nonadherent mesenchymal progenitor cells into adherent osteoblast precursors .
elevated levels of a low - molecular - weight pg - like molecule have been detected in the plasma of patients with fop .
stromal cell derived factor 1 is a mediator of lesion formation in a mouse model of pulmonary fibrosis and may signal circulating fibrocytes to homing regions that eventually become fibrotic .
heterotopic bone formation may occur in pulmonary fibrosis and the circulating fibrocytes are abundant in patient with fop with active exacerbations .
taken together , these observations suggest a plausible mechanism for extraskeletal ossification in fop that invokes the recruitment of circulating osteogenic cells . whereas bmp-4 may induce ectopic ossification in animal models , it is known to be dysregulated in fop .
children who have fop appear normal at birth except for congenital malformations of the great toes .
typically , during the first decade of life , sporadic episodes of painful soft tissue swellings ( flare - ups ) occur and are commonly mistaken for tumors .
however , in our patient , no malformations of the great toes were clearly detected except slight valgus of right great toe .
the ossification started from occipital bone and posterior paravertebral soft tissue , which caused limitation of neck movement , whereas ossification on both humerus and scapula caused limitation of the shoulder joint movement . eventually , the ossification process forms bridges between axial bones .
most of literature stated that ectopic ossification usually started from the cervical area , then extended down paravertebrally to lower back and progressively formed
bony projections in our case were similar to multiple exostoses , whereas the location of lesions was uncommon for that kind of  tumor  . based on our clinical diagnosis , we performed excision of  all multiple exostoses  which were located from occipital bone until lumbar spine and the bridging bones between scapula and both bilaterally .
histopathology showed fragmented tissue consisting of cartilaginous component and irregular underlying bony trabeculae ( endochondral ossification ) .
there was also bone marrow between trabeculae , a histopathologic feature commonly found in exostosis .
at discussion in our routine fop , we re - evaluated the slides and processed the whole specimen .
microscopically the specimen also showed fibrous tissue , skeletal muscle mixed with endochondral ossification , and foci of calcification .
although histologically , a very early fop lesions look identical to the fibroproliferative lesions of aggressive juvenile fibromatosis , in aggressive juvenile fibromatosis , the lesions do not progress beyond the connective tissue growth phase , whereas in fop , they mature through an endochondral process to form cartilage and bone
one study mentioned that nearly 90% of patients with fop worldwide are misdiagnosed and 67% undergo dangerous and unnecessary diagnostic procedures .
tumor , fibromatosis , bunion , myositis ossificans , calcified hematoma , exostoses , and also ankylosing spondylitis   are considered in the differential diagnosis .
surgical therapy which aims to improve range of movement in this patient has proven to trigger further ossification . in this patient ,
follow up , she presented with the same complaint and similar range of movement of shoulder and cervical spine as before surgery .
radiation therapy may be considered after surgery to prevent recurrence , but there is no clear evidence that radiotherapy is effective in patients with fop , except in small number of patients .
medications that have theoretical application to fop such as leukotriene inhibitor and investigational new drugs such as signal transduction inhibitor and monoclonal targeting acvr1 may show a promising result in fop patient . research in fop has reached genetic level , but not yet in molecular level that it might produce a gene therapy .
so , we have to make early clinical diagnosis and the mainstay of therapy is education to the patient and family to prevent further trauma .
it is difficult to diagnose and manage fop , therefore delayed or misdiagnosis and also inappropriate management is common .
although rare , we should consider fop as a differential diagnosis in patient complaining of multiple masses with soft tissue ossification .
we should avoid dangerous and unnecessary diagnostic procedure as well as inappropriate management which may lead to futher exacerbations .
 introduction : fibrodysplasia ossificans progressiva ( fop ) is a rare autosomal dominant genetic disorder and characterized by postnatal progressive heterotopic ossification of the connective tissue 
 . there are difficulties in diagnosing fop , thus delayed or misdiagnosis and mismanagement is common.3d printers have now become widely available and inexpensive , and can be used to rapidly produce life - size models based on ct scans of an individual patient . 
 the availability of patient specific , accurate and detailed models of complex acetabular fractures can aid planning of surgical management on a patient specific basis.case report : we present the diagnosis and surgical management of a 9-year old indonesian girl with fop . 
 she presented with extensive involvement of cervical spine and both shoulders . 
 total excision of occipito - cervico - lumbar and paravertebral ossification and also exostoses at bilateral shoulder was done . at three years 
 follow up , she had local recurrence with similar range of movement of the shoulder and cervical spine.conclusion:fop is an extremely rare case . 
 it is difficult to diagnose and manage fop , therefore delayed or misdiagnosis and also inappropriate management is common . 
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Case Report
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