- Email: [email protected]
Myositis ossificans progressiva: five generations where the disease was exclusively limited to the maxillofacial region
Copyright 9 Munksgaard1998 ln~nat;~alJoumal
Int. J. Oral Maxillofac. Surg. 1998; 27." 299-302 Printed in Denmark. All rights reserved
Ord& Maxal ad Surgay ISSN 0901-5027
Pathology
Myositis ossificans progressiva: five generations where the disease was exclusively limited to the maxillofacial region
C. Debeney-Bruyerre 1, L. Chlkhsni 1, R. Lockhart 1, E. Favre-Dauvergne ~, B. Weschler 2, J. Ch. Bertrand 1, F. Gullbert 1 1Clinique et UFR de Stomatologie et de Chirurgie Maxillo-facial, H6pital de la Salp6td~re, 2Service de M6decine Interne, H6pital de la Piti6, Pads, France
A case report C Debeney-Bruyerre, L. ChikhanL R. Lockhart, E. Favre-Dauvergne, B. Weschler, J. Ch. Bertrand, F. Guilbert: Myositis ossificans progressiva: five generations where the disease was exclusively limited to the maxillofacial region. A case report. Int. J. Oral Maxillofac. Surg. 1998; 27: 299-302. 9 Munksgaard, 1998
Abstract. Myositis ossificans progressiva is an unusual autosomal-dominant inherited disease characterized by congenital malformations and osseous metaplasia of the fascia of the muscles and connective tissue leading to ossification of the relevant area. The case report is remarkable in that eight members of the same family over five generations manifested the exclusive localization of the disease in the maxillofacial region.
Myositis ossificans progressiva (MOP) is a rare autosomal-dominant interested disease characterized by multiple congenital malformations and osseous metaplasia of the muscles and connective tissue leading to progressive ossification of the relevant areas. The presented case is unusual by its exclusivity to the maxillofacial region and by the fact that seven other members of the same family have been afiticted over five generations. It will describe the pathophysiology of the disease, and discuss the therapeutic options for the appropriate treatment of the patient.
plaining of painful swelling of the left angle of the mandible, pain in the right angle of the mandible, and restricted mandibular opening that had appeared 15 days earlier. Her past medical history included trauma to the right angle of the mandible, three months before, and the surgical re-
: i;)i;
~
Key words: myositis ossificans progressiva; tdsmus; inherited disease. Accepted for publication 10 January 1998
moval of her four third molars under general anaesthesia, two months prior to her visit. At that time, after an uneventful postoperative course, mandibular opening returned to normal. Clinical examination revealed painful trismus which restricted mandibular open-
....
Case report A 2l-year-old woman, in good general health, presented in September 1994 com-
Fig. 1. Orthopantomogram showing diffuse calcifications of right sigmoid notch.
300
D e b e n e y - B r u y e r r e et al.
ing to 25 mm, lateral displacement of the mandible, inability of the condyle to move upon translation, and pain in the mandibular coronoid process upon palpation. A panorex radiograph (Fig. 1) revealed visible third molar sockets as a result of the extractions, an advanced position of the right mandibular condyle and some diffuse radiopaque structures at the right sigmoid notch, which had not been present in the preoperative films. Computed tomography (CT) (Fig. 2) performed at that time showed an isolated calcification along the distribution of the right lateral pterygoid muscle. Six weeks later, the restriction of the mandibular opening had become almost complete. Magnetic resonance imaging (MRI) was performed (Fig. 3) and confirmed calcification of the right lateral
l
x
sj ~f
Fig. 2. CT scan showing isolated calcification along right lateral pterygoid muscle.
pterygoid muscle. A T2-weighted hypersignal in the left medial pterygoid muscle was detected. The progressive calcification of this lesion was confirmed three weeks later by CT scan (Fig. 4) which illustrated not only the previous calcification of the right lateral pterygoid muscle but also calcification of the left medial pterygoid muscle. A complete examination did not reveal ossification in any other areas especially in the cervical vertebrae. Clinically and radiographically her hands and feet were normal, as were the complete laboratory studies. A family history enabled the establishment of pedigree in which the possible penetrance of the disease in five generations is depicted (Fig. 5): seven other members of the family over five generations had been similarly affected. This disease manifested in every generation, 75% o f those afflicted were women, and the involvement was exclusively in the maxillofacial region. They all had absolute restriction of mandibular opening which manifested at the age of 23. The hands and feet were normal and the average life span was 73 years. In our patient, the bilateral ossification of the muscles of mastication and the family history of such an involvement led to the diagnosis of MOP despite the absence of congenital malformations. A genetic linkage study of the family would have been informative but unfortunately the family refused to participate. It was decided not to attempt surgery. The patient was treated with nonsteroidal anti-inflammatory drugs and then calcium chelators. Although the clinical evolution of the disease seemed to be stabilized, a control CT scan showed new calcifications of the left masseter muscle and the left temporalis muscle. A CT scan performed one year later did not reveal further progression of the disease but continued to reveal the calcifications of the right and left pterygoid, temporalis and masseter muscles.
Discussion
)
,
Fig. 3. MRI showing calcification of fight lateral pterygoid muscle and T2-weighted hypersignal of left medial pterygoid muscle.
MOP, also called Munchmeyer's disease or fibrodysplasia ossificans progressiva, is a rare autosomal-dominant inherited disease o f varying expression and penetrance; 95% o f the cases are sporadic 14. The incriminating gene is located on chromosome 20 and codes for the synthesis o f bone morphogenetic protein 2a z3. The disease exhibits no sexual or racial predilection. Patients suffering from this disease are fertile 9,29 and, therefore genetic counselling is of eminent importance. Clinically, M O P is characterized by congenital malformations coupled with progressive ossification o f the striated muscles. Congenital malfor-
i
Fig. 4. C T scan three weeks after M R | shows calcification of previously detected right lateral pterygoid muscle and new ossification of left medial pterygoid muscle.
,
,rh
HI I
,in
4
,0
s~
0--" I--I-Fig. 5. Pedigree showing that eight family members have probably been afflicted over five generations.
mations 6,8,25,27,28 include microdactyly of the big toe and, more rarely, the thumb, hallus valgus and vertebral malformation, and are present in 80% of cases. They are transmitted with complete penetrance. Should one o f the two parents be afflicted, the in utero ultrasonographic examination revealing an abnormal big toe indicates the transmission o f the disease to the fetus. Ossification of striated muscles 4,5,19,21,26,27 manifests around the age of five and appears as a constant, cold, painful muscle swelling. The individual's overall general condition remains good. Within three to four weeks,
Myositis ossificansprogressiva this lesion becomes ossified, immobilizing the associated joints. The involvement preferentially affects the muscles of the cervical or dorsal-lumbar vertebrae, the pelvic and pectoral girdles, and the limbs. Involvement of the spine leads to scoliosis and subsequent restrictive respiratory insufficiency. Trauma, iatrogenic or not, is considered a triggering factor. The disease progresses by successive bilateral sporadic episodes in a cephalocaudal-axial to peripheral direction, affecting one or several muscles. Each episode leaves functional sequelae that are additive over time leading to a bedridden state. On average, death occurs around the age of 35 years. Maxillofacial involvement 3,5,1~176 leading to the permanent restriction of mandibular opening is seen in 55% of cases and occurs around the average age of 17.5 years. Other pathologic conditions that are seen are: synovial chondromatosis, pseudo-parahypothyroidism, polyostotic fibrodysplasia, transmission deafness and baldness i,6,H,27. CT scanning 16,2~ without injection of contrast medium usually shows hypodense swelling along the muscle well before these calcifications are evident on standard radiographs. Once the lesions are formed, multifocal sites of ossification can be seen within the soft tissues. Ultrasonography 1,8,17 shows a thickening of the soft tissues with the presence of a central echogenic zone surrounded by a well defined hypoechogenic zone about three months before the calcifications can be visualized on radiographs. As the disease progresses this technique usually reveals solid ossified nodules. An M R I 2,15 is able to illustrate an even earlier T2-weighted hypersignal at the level of the affected muscle as was evident in our patient's left medial pterygoid. Scintigraphy 13A5 may reveal abundant isotope uptake at the level of ectopic ossification sites at the onset of the disease. Because this procedure gives a view of the entire body, known loci of ossification can be monitored and new sites, still undetectable by radiographic examination, can be identified. Standard radiographs 13,27 can only detect signs of ossification after 6-12 months of progression. They show calcified diffuse opacities with irregular contours. Once the lesions have evolved, the radiographs help to visual-
ize the progression of the ossification which follows the contour of the affected musculature. In our patient, bone formation appeared after 1.5 months. The laboratory tests usually reveal no abnormality, and phosphate and calcium values are within normal limits. Biopsy is contraindicated because any trauma can trigger a new episode of ossification. In practice, however, a biopsy is often performed at the onset of the disease in order to eliminate the possibility of a malignant tumour. Two successive phases of the disease have been described 12. The early phase, with abundant primary vascular cells and angiogenesis, and the ossification phase, where premature ectopic bone is seen. Osteogenesis is always endochondral. The only possibility that exists in the differential diagnosis is post-traumatic myositis ossificans circumscripta. This entity is usually limited to a single and dearly delineated painful swelling of the soft tissues, that occurs in young adults subsequent to trauma. It may be treated surgically and there is usually no recurfence after the lesion has been excised. The poor understanding of the pathophysiology of MOP explains the lack of treatment protocols capable of stopping the progression of the disease. Numerous medical regimens 1,7,11,18,19,22,25,27,3~ have been prescribed including calcitonin, nonsteroidal anti-inflammatory drugs, antimitotic agents, isotretinoin, and warfarin, but their efficacy has yet to be proven. A calcium chelator, like Didronel | (Procter & Gamble, Neuilly-sur-Seine, France), may be more effective. Surgery 5,7,13,2s exposes the patient to the risk of exacerbation and recurrence within two months and can trigger an accelerated progression of the disease. Respiratory physical therapy can delay the appearance of the restrictive syndrome and is also indicated for episodes of bronchial superinfection. This familial study is remarkable because of the completeness of its pedigree, and the exclusivity of the maxillofacial manifestation of the disease. In all of the affected members, there was an absence of congenital malformations and late onset of symptoms. Women were predominantly affected and the disease had no effect on the life expectancy of the patient. The initiation of the appearance of the condition in the patient is
301
probably the trauma she received to her mandible, followed by the removal of her third molars prior to manifestation of the condition.
References 1. Bguh~ L, GIAMMARXAP, TOZZIMC, CAMPARCOLAD, SCOPINAgOE IMPERATOC. Fibrodysplasia ossificans progressiva. An l 1-year-old boy treated with a diphosphonate. Act Paed Scand 1990: 79: 9948. 2. CARONKH, DI PIETROMA, AISENAM, HEIDELBERGERgP, PHILLIPSWA, MARTELW. MR imaging of early fibrodysplasia ossificans progressiva. J Comput Assist Tomogr 1990: 14: 318-21. 3. CERN~AP, BATAILLER, CR~PYC, MAZZA R, TONNELmRP. Constriction permanente htrtditaires des m~choires. Rev Stomatol: 1965: 66: 59-64. 4. COHEN RB, HAHN GV, TABASJA, et al. The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. J Bone Joint Surg (Am) 1993: 75: 215-9. 5. CON'NORJM, EVANSDAP. Extra-articular ankylosis in fibrodysplasia ossificans progressiva. BrJ Oral Surg 1982: 20: 117-21. 6. CON'NORJM, SKmTON H, LUNT PW. A three generation family with fibrodysplasia ossificans progressiva [see comments]. J Med Genet 1993: 30: 687-9. 7. CROFFOROLJ, BRAHIMJS, ZASLOFFMA, MARnm JC. Failure of surgery and isotretinoin to relieve jaw immobilization in fibrodysplasia ossificans progressiva: report of two cases. J Oral Maxillofac Surg 1990: 48: 204-8. 8. DALTROFFG, LUTZ P, BELLOCQP, et al.
Fibromatose et fibrodysplasie ossificante progressive: un erreur diagnostique 6vitable. Arch Fr Pediatr 1992: 49: 441-4. 9. Fox S, KHOURY A, MOOTAaAR H, Gm~a~VALDET. Myositis ossificans progressiva and pregnancy. Obstet Gyne~ol 1987: 69: 453-5. 10. IRIRTEJI, COULONJR, REYCHLERH. Ankylose temporo-mandibulaire et myosite ossifiante progressive. Rev Stomatol Chir Maxillofac 1990: 91: 51-5. 11. KALIFAG, ADAMSBAUMC, JoB-DESLANDE C, DUBOUSSET J. Fibrodysplasia ossi-
ficans progressiva and synovial chondromatosis. Pediatr Radiol 1993: 23: 913. 12. KAPLAN FS, TABASJA, GANNON FH, FINKELG, HAHNGV, ZASLOFFMA. The histopathology of fibrodysplasia ossificans progressiva. An endochondral process. J Bone Joint Surg (Am) 1993: 75: 220-30. 13. KAPLANFS, STREARCM, ZASLOFFMA. Radiographic and scintigraphic features of modeling and remodeling in the heterotopic skeleton of patients who have
302
Debeney-Bruyerre et al.
fibrodysplasia ossificans progressiva. Clin Orthop 1994: 304: 238--47. 14. KAPLAN FS, MCCLusKEY W, HAHN G, TABASJA, MtmNKEM, ZASLOFFMA. Genetic transmission of fibrodysplasia ossificans progressiva. Report of a family. J Bone Joint Surg (Am) 1993: 75: 1214-20. 15. KRANSDORF M J, MEIS JM. From the archives of the AFIE Extraskeletal osseous and cartilaginous tumors of the extremities. Radiographics 1993: 13: 85384. 16. LINDHOUT D, GOLDING RP, TAETS VAN AMERONGEN AH. Fibrodysplasia ossificans progressiva: current concepts and the role of CT in acute changes. Pediatr Radiol 1985: 15: 211-3. 17. McATE-ER EJ, HALLAM LA, HENDRY GM. Ultrasonic appearances of the early changes in fibrodysplasia ossiiicans progressiva. Br J Radiol 1990: 63: 809-12. 18. MOORE SE, JUMP AA, SMILEYJD. Effect of warfarin sodium therapy on excretion of 4-carboxy-L-glutamicacid in sclerodermia, dermatomyosis, and myosite ossificans progressiva. Arthritis Rheum 1986: 29: 344-51. 19. NEWTON MC, ALLEN PW, RYAN DC. Fibrodyspla~ia ossificans progressiva. Br J Anaesth 1990: 64: 246-50. 20. NUNELLY JF, YOSSEN PS. Computed tomographic finding in patients with
limited jaw movement due to myositis ossificans progressiva. J Oral Maxillofac Surg 1986: 44: 818-21. 21. PAZZAGLI G, BELLUFI A, COLOMBO A, M ~ c m A, Coco L, CECILIA,. Myositis ossificans in the new born. J Bone Joint Surg (Am) 1986: 68: 456-8. 22. PmTTE E, REYCI-ILER H. Traitd de pathologic buccale et maxillo-faciale. Bruxelles: De Boek Universitt, 1991: 1465~. 23. RAG V~, LOrrL~R C, W o z m JM, HANSMANNI. The gene for bone morphogenetic protein 2a (bmp2a) is localized to human chromosome 20p 12 by radioactive and nonradioactive in situ hybridization. Hum Genet 1992: 90: 299-302. 24. RErmo JW, HILL SC, FANG M, MARrNI J, ZASLOFF MA. Fibrodysplasia ossificans progressiva: CT appearance. Radiology 1986: 159: 153-7. 25. RENTON P, PARKIN SF, STAMP TCB. Abnormal temporo-mandibular joints in fibrodysplasia ossificans progressiva. Br J Oral Surg 1982: 20: 31-8. 26. ROCKE DM, ZASLOFF M, PEEPER J, COHEN RB, KAPLAN US. Age- and joint-specific risk of initial heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. Clin Orthop 1994: 301: 243-8. 27. SEGUINP, DELMASP, BOUVmRR, FREIDEL
M. Constriction permanente des maxillaircsrtv~latriced'une myositc ossifiante progressive.Rev Stomatol ClairMaxillofac 1987: 88.'190-5. 28. SHAI-IPB, ZASLOFe M A , DRLrMMOm) D, KAPLAN FS. Spinal deformity in patients who have fibrodysplasia ossificans progressiva. J Bone Joint Surg (Am) 1994: 76: 1442-50. 29. THORNTON YS, BIRNBAUMSJ, Lmowrrz N. A viable pregnancy in patient with Myositis ossificans progressiva. Am J Obstet Gynecol 1987: 156: 577-8. 30. ZASLOFF M, HILL S, MARINI JC. Dense metaphysal bands and growth arrest associated with isoretinoin therapy. Am J Dis Child 1988: 142: 316-8.
Address:
Dr C. Debeney-Bruyerre Service de Stomatologie et Chirurgie Maxillo-facial (Prof. J. Ch. Bertrand) Groupe Hospitalier Piti~-Salp#tri~re 4743 Blvd de l'Htpital F-75651 Paris Cedex 13 France E-mail." [email protected].
Int. J. Oral Maxillofac. Surg. 1998; 27." 299-302 Printed in Denmark. All rights reserved
Ord& Maxal ad Surgay ISSN 0901-5027
Pathology
Myositis ossificans progressiva: five generations where the disease was exclusively limited to the maxillofacial region
C. Debeney-Bruyerre 1, L. Chlkhsni 1, R. Lockhart 1, E. Favre-Dauvergne ~, B. Weschler 2, J. Ch. Bertrand 1, F. Gullbert 1 1Clinique et UFR de Stomatologie et de Chirurgie Maxillo-facial, H6pital de la Salp6td~re, 2Service de M6decine Interne, H6pital de la Piti6, Pads, France
A case report C Debeney-Bruyerre, L. ChikhanL R. Lockhart, E. Favre-Dauvergne, B. Weschler, J. Ch. Bertrand, F. Guilbert: Myositis ossificans progressiva: five generations where the disease was exclusively limited to the maxillofacial region. A case report. Int. J. Oral Maxillofac. Surg. 1998; 27: 299-302. 9 Munksgaard, 1998
Abstract. Myositis ossificans progressiva is an unusual autosomal-dominant inherited disease characterized by congenital malformations and osseous metaplasia of the fascia of the muscles and connective tissue leading to ossification of the relevant area. The case report is remarkable in that eight members of the same family over five generations manifested the exclusive localization of the disease in the maxillofacial region.
Myositis ossificans progressiva (MOP) is a rare autosomal-dominant interested disease characterized by multiple congenital malformations and osseous metaplasia of the muscles and connective tissue leading to progressive ossification of the relevant areas. The presented case is unusual by its exclusivity to the maxillofacial region and by the fact that seven other members of the same family have been afiticted over five generations. It will describe the pathophysiology of the disease, and discuss the therapeutic options for the appropriate treatment of the patient.
plaining of painful swelling of the left angle of the mandible, pain in the right angle of the mandible, and restricted mandibular opening that had appeared 15 days earlier. Her past medical history included trauma to the right angle of the mandible, three months before, and the surgical re-
: i;)i;
~
Key words: myositis ossificans progressiva; tdsmus; inherited disease. Accepted for publication 10 January 1998
moval of her four third molars under general anaesthesia, two months prior to her visit. At that time, after an uneventful postoperative course, mandibular opening returned to normal. Clinical examination revealed painful trismus which restricted mandibular open-
....
Case report A 2l-year-old woman, in good general health, presented in September 1994 com-
Fig. 1. Orthopantomogram showing diffuse calcifications of right sigmoid notch.
300
D e b e n e y - B r u y e r r e et al.
ing to 25 mm, lateral displacement of the mandible, inability of the condyle to move upon translation, and pain in the mandibular coronoid process upon palpation. A panorex radiograph (Fig. 1) revealed visible third molar sockets as a result of the extractions, an advanced position of the right mandibular condyle and some diffuse radiopaque structures at the right sigmoid notch, which had not been present in the preoperative films. Computed tomography (CT) (Fig. 2) performed at that time showed an isolated calcification along the distribution of the right lateral pterygoid muscle. Six weeks later, the restriction of the mandibular opening had become almost complete. Magnetic resonance imaging (MRI) was performed (Fig. 3) and confirmed calcification of the right lateral
l
x
sj ~f
Fig. 2. CT scan showing isolated calcification along right lateral pterygoid muscle.
pterygoid muscle. A T2-weighted hypersignal in the left medial pterygoid muscle was detected. The progressive calcification of this lesion was confirmed three weeks later by CT scan (Fig. 4) which illustrated not only the previous calcification of the right lateral pterygoid muscle but also calcification of the left medial pterygoid muscle. A complete examination did not reveal ossification in any other areas especially in the cervical vertebrae. Clinically and radiographically her hands and feet were normal, as were the complete laboratory studies. A family history enabled the establishment of pedigree in which the possible penetrance of the disease in five generations is depicted (Fig. 5): seven other members of the family over five generations had been similarly affected. This disease manifested in every generation, 75% o f those afflicted were women, and the involvement was exclusively in the maxillofacial region. They all had absolute restriction of mandibular opening which manifested at the age of 23. The hands and feet were normal and the average life span was 73 years. In our patient, the bilateral ossification of the muscles of mastication and the family history of such an involvement led to the diagnosis of MOP despite the absence of congenital malformations. A genetic linkage study of the family would have been informative but unfortunately the family refused to participate. It was decided not to attempt surgery. The patient was treated with nonsteroidal anti-inflammatory drugs and then calcium chelators. Although the clinical evolution of the disease seemed to be stabilized, a control CT scan showed new calcifications of the left masseter muscle and the left temporalis muscle. A CT scan performed one year later did not reveal further progression of the disease but continued to reveal the calcifications of the right and left pterygoid, temporalis and masseter muscles.
Discussion
)
,
Fig. 3. MRI showing calcification of fight lateral pterygoid muscle and T2-weighted hypersignal of left medial pterygoid muscle.
MOP, also called Munchmeyer's disease or fibrodysplasia ossificans progressiva, is a rare autosomal-dominant inherited disease o f varying expression and penetrance; 95% o f the cases are sporadic 14. The incriminating gene is located on chromosome 20 and codes for the synthesis o f bone morphogenetic protein 2a z3. The disease exhibits no sexual or racial predilection. Patients suffering from this disease are fertile 9,29 and, therefore genetic counselling is of eminent importance. Clinically, M O P is characterized by congenital malformations coupled with progressive ossification o f the striated muscles. Congenital malfor-
i
Fig. 4. C T scan three weeks after M R | shows calcification of previously detected right lateral pterygoid muscle and new ossification of left medial pterygoid muscle.
,
,rh
HI I
,in
4
,0
s~
0--" I--I-Fig. 5. Pedigree showing that eight family members have probably been afflicted over five generations.
mations 6,8,25,27,28 include microdactyly of the big toe and, more rarely, the thumb, hallus valgus and vertebral malformation, and are present in 80% of cases. They are transmitted with complete penetrance. Should one o f the two parents be afflicted, the in utero ultrasonographic examination revealing an abnormal big toe indicates the transmission o f the disease to the fetus. Ossification of striated muscles 4,5,19,21,26,27 manifests around the age of five and appears as a constant, cold, painful muscle swelling. The individual's overall general condition remains good. Within three to four weeks,
Myositis ossificansprogressiva this lesion becomes ossified, immobilizing the associated joints. The involvement preferentially affects the muscles of the cervical or dorsal-lumbar vertebrae, the pelvic and pectoral girdles, and the limbs. Involvement of the spine leads to scoliosis and subsequent restrictive respiratory insufficiency. Trauma, iatrogenic or not, is considered a triggering factor. The disease progresses by successive bilateral sporadic episodes in a cephalocaudal-axial to peripheral direction, affecting one or several muscles. Each episode leaves functional sequelae that are additive over time leading to a bedridden state. On average, death occurs around the age of 35 years. Maxillofacial involvement 3,5,1~176 leading to the permanent restriction of mandibular opening is seen in 55% of cases and occurs around the average age of 17.5 years. Other pathologic conditions that are seen are: synovial chondromatosis, pseudo-parahypothyroidism, polyostotic fibrodysplasia, transmission deafness and baldness i,6,H,27. CT scanning 16,2~ without injection of contrast medium usually shows hypodense swelling along the muscle well before these calcifications are evident on standard radiographs. Once the lesions are formed, multifocal sites of ossification can be seen within the soft tissues. Ultrasonography 1,8,17 shows a thickening of the soft tissues with the presence of a central echogenic zone surrounded by a well defined hypoechogenic zone about three months before the calcifications can be visualized on radiographs. As the disease progresses this technique usually reveals solid ossified nodules. An M R I 2,15 is able to illustrate an even earlier T2-weighted hypersignal at the level of the affected muscle as was evident in our patient's left medial pterygoid. Scintigraphy 13A5 may reveal abundant isotope uptake at the level of ectopic ossification sites at the onset of the disease. Because this procedure gives a view of the entire body, known loci of ossification can be monitored and new sites, still undetectable by radiographic examination, can be identified. Standard radiographs 13,27 can only detect signs of ossification after 6-12 months of progression. They show calcified diffuse opacities with irregular contours. Once the lesions have evolved, the radiographs help to visual-
ize the progression of the ossification which follows the contour of the affected musculature. In our patient, bone formation appeared after 1.5 months. The laboratory tests usually reveal no abnormality, and phosphate and calcium values are within normal limits. Biopsy is contraindicated because any trauma can trigger a new episode of ossification. In practice, however, a biopsy is often performed at the onset of the disease in order to eliminate the possibility of a malignant tumour. Two successive phases of the disease have been described 12. The early phase, with abundant primary vascular cells and angiogenesis, and the ossification phase, where premature ectopic bone is seen. Osteogenesis is always endochondral. The only possibility that exists in the differential diagnosis is post-traumatic myositis ossificans circumscripta. This entity is usually limited to a single and dearly delineated painful swelling of the soft tissues, that occurs in young adults subsequent to trauma. It may be treated surgically and there is usually no recurfence after the lesion has been excised. The poor understanding of the pathophysiology of MOP explains the lack of treatment protocols capable of stopping the progression of the disease. Numerous medical regimens 1,7,11,18,19,22,25,27,3~ have been prescribed including calcitonin, nonsteroidal anti-inflammatory drugs, antimitotic agents, isotretinoin, and warfarin, but their efficacy has yet to be proven. A calcium chelator, like Didronel | (Procter & Gamble, Neuilly-sur-Seine, France), may be more effective. Surgery 5,7,13,2s exposes the patient to the risk of exacerbation and recurrence within two months and can trigger an accelerated progression of the disease. Respiratory physical therapy can delay the appearance of the restrictive syndrome and is also indicated for episodes of bronchial superinfection. This familial study is remarkable because of the completeness of its pedigree, and the exclusivity of the maxillofacial manifestation of the disease. In all of the affected members, there was an absence of congenital malformations and late onset of symptoms. Women were predominantly affected and the disease had no effect on the life expectancy of the patient. The initiation of the appearance of the condition in the patient is
301
probably the trauma she received to her mandible, followed by the removal of her third molars prior to manifestation of the condition.
References 1. Bguh~ L, GIAMMARXAP, TOZZIMC, CAMPARCOLAD, SCOPINAgOE IMPERATOC. Fibrodysplasia ossificans progressiva. An l 1-year-old boy treated with a diphosphonate. Act Paed Scand 1990: 79: 9948. 2. CARONKH, DI PIETROMA, AISENAM, HEIDELBERGERgP, PHILLIPSWA, MARTELW. MR imaging of early fibrodysplasia ossificans progressiva. J Comput Assist Tomogr 1990: 14: 318-21. 3. CERN~AP, BATAILLER, CR~PYC, MAZZA R, TONNELmRP. Constriction permanente htrtditaires des m~choires. Rev Stomatol: 1965: 66: 59-64. 4. COHEN RB, HAHN GV, TABASJA, et al. The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. J Bone Joint Surg (Am) 1993: 75: 215-9. 5. CON'NORJM, EVANSDAP. Extra-articular ankylosis in fibrodysplasia ossificans progressiva. BrJ Oral Surg 1982: 20: 117-21. 6. CON'NORJM, SKmTON H, LUNT PW. A three generation family with fibrodysplasia ossificans progressiva [see comments]. J Med Genet 1993: 30: 687-9. 7. CROFFOROLJ, BRAHIMJS, ZASLOFFMA, MARnm JC. Failure of surgery and isotretinoin to relieve jaw immobilization in fibrodysplasia ossificans progressiva: report of two cases. J Oral Maxillofac Surg 1990: 48: 204-8. 8. DALTROFFG, LUTZ P, BELLOCQP, et al.
Fibromatose et fibrodysplasie ossificante progressive: un erreur diagnostique 6vitable. Arch Fr Pediatr 1992: 49: 441-4. 9. Fox S, KHOURY A, MOOTAaAR H, Gm~a~VALDET. Myositis ossificans progressiva and pregnancy. Obstet Gyne~ol 1987: 69: 453-5. 10. IRIRTEJI, COULONJR, REYCHLERH. Ankylose temporo-mandibulaire et myosite ossifiante progressive. Rev Stomatol Chir Maxillofac 1990: 91: 51-5. 11. KALIFAG, ADAMSBAUMC, JoB-DESLANDE C, DUBOUSSET J. Fibrodysplasia ossi-
ficans progressiva and synovial chondromatosis. Pediatr Radiol 1993: 23: 913. 12. KAPLAN FS, TABASJA, GANNON FH, FINKELG, HAHNGV, ZASLOFFMA. The histopathology of fibrodysplasia ossificans progressiva. An endochondral process. J Bone Joint Surg (Am) 1993: 75: 220-30. 13. KAPLANFS, STREARCM, ZASLOFFMA. Radiographic and scintigraphic features of modeling and remodeling in the heterotopic skeleton of patients who have
302
Debeney-Bruyerre et al.
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Address:
Dr C. Debeney-Bruyerre Service de Stomatologie et Chirurgie Maxillo-facial (Prof. J. Ch. Bertrand) Groupe Hospitalier Piti~-Salp#tri~re 4743 Blvd de l'Htpital F-75651 Paris Cedex 13 France E-mail." [email protected].