- Email: [email protected]
A Rare Sporadic Case of Camurati-Engelmann Disease With Jaw Involvement
Accepted Manuscript A rare sporadic case of Camurati Engelmann disease with jaw involvement Maria Fyrgiola, Violeta Lianou, Konstantinos Katoumas, Ioannis Dimopoulos PII:
S0278-2391(17)30391-9
DOI:
10.1016/j.joms.2017.03.059
Reference:
YJOMS 57752
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 20 February 2017 Revised Date:
29 March 2017
Accepted Date: 31 March 2017
Please cite this article as: Fyrgiola M, Lianou V, Katoumas K, Dimopoulos I, A rare sporadic case of Camurati Engelmann disease with jaw involvement, Journal of Oral and Maxillofacial Surgery (2017), doi: 10.1016/j.joms.2017.03.059. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT A rare sporadic case of Camurati Engelmann disease with jaw involvement.
Fyrgiola Maria MD, DDS, Resident of the department of Oral and Maxillofacial
Athens, Greece Corresponding author contact information: Fyrgiola Maria
RI PT
Surgery, General Hospital “G. Gennimatas”, Mesogeion 154 Str., GR 11527,
Telephone (cell phone): +30-6974623681
M AN U
Telephone (home): +30- 2105023411
SC
Address (home): , Ikarias 11, GR 13231, Petroupoli, Athens, Greece
Fax (home): +30-
E-mail: [email protected] Co-authors
TE D
1. Violetta Lianou MD, DDS, MSc, PhD, Senior Registrar of the department of Oral and Maxillofacial Surgery, General Hospital “G.
EP
Gennimatas”, Mesogeion 154 Str., GR 11527, Athens, Greece
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2. Konstantinos Katoumas MD, DDS, MSc, PhD, Resident of the department of Oral and Maxillofacial Surgery, General Hospital “G. Gennimatas”, Mesogeion 154 Str., GR 11527, Athens, Greece
3. Ioannis Dimopoulos DDS, Head of the department of Oral and Maxillofacial Surgery, General Hospital “G. Gennimatas”, Mesogeion 154 Str., GR 11527, Athens, Greece
ACCEPTED MANUSCRIPT A rare sporadic case of Camurati Engelmann disease with jaw involvement. Maria Fyrgiola, Violeta Lianou, Konstantinos Katoumas, Ioannis Dimopoulos Department of Oral and Maxillofacial Surgery, Georgios Gennimatas General Hospital, 154 Mesogeion Str., Athens, GR 11527, Greece
Camurati-Engelmann disease Progressive diaphyseal dysplasia Tori Mandible enlargement
SC
Abstract
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Keywords
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Camurati-Engelmann disease (CED), or progressive diaphyseal dysplasia, is an uncommon bone dysplasia, which is inherited in an autosomal dominant pattern. The disease mainly affects the diaphyses of the long bones, but can also induce sclerotic changes to the facial skeleton and the skull base. The diagnosis of CED is based on clinical and radiological features. The purpose of the article is to present the clinical and radiological characteristics of the jaws, as shown in cone-beam computed tomography images of a 46-year old-female diagnosed with CED.
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Introduction
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In 1922, Camurati first reported the disease, followed by Engelmann in 1929. Camurati-Engelmann disease, also known as progressive diaphyseal dysplasia, is a rare autosomal dominant disorder, resulting from mutations of the TGFβ1(transforming growth factor) gene (1). The responsible gene has been identified on chromosome 19q13. TGFβ1 plays a significant role in bone remodeling, stimulating bone formation and suppressing bone resorption under normal circumstances. (1), (2) Moreover, it suppresses myoblast maturation and adipogenesis and it impedes muscle reconstruction. (3) This condition typically results in cortical thickening of the diaphysis of the long bones and sclerotic alterations of the skull base (4). The diagnosis is challenging, due to lack of published guidelines. Approximately 306 cases have been reported so far (5). In our case we emphasize on the clinical and radiological manifestations of the facial skeleton in a female patient. Case Report In November 2015, a 46-year-old female was self-referred to the outpatient department of the oral and maxillofacial clinic, due to the presence of multiple firm nodules of the maxillary labial gingiva and of the hard palate. She reported that she had been diagnosed with CED since 2000 and has been under regular observation by a rheumatologist (Fig.1) .She had no other health problems. The patient has been treated with intravenous zoledronic
ACCEPTED MANUSCRIPT acid, prednisolone and alphacalcidol since diagnosis. During this time, she has developed presbyopia, hearing loss and walking abnormalities, progressive decrease in mouth opening and alterations of the external features of her face. None of her family’s members had similar symptoms, therefore we assumed she was a sporadic case.
M AN U
SC
RI PT
On physical examination the patient had an average height , a normal physical and mental growth, and difficulty in hearing and walking. Frontal bossing, bilateral exophthalmos and facial asymmetry without midline shift coexisted. The shape of the face was round, while the midface was normal. The mandible was enlarged, with increased height and width, particularly on the right side. The dental occlusion was Angle’s class II, division 2. The mouth opening was reduced (Fig. 2) .The dental eruption was normal and the maxillary first premolars had been extracted. There were maxillary tori, bilaterally, among maxillary lateral incisor and premolarand apically of the first molars (Fig.3) . A torus palatinus was noted at the midline of the hard palate (Fig.4) . We recommended the patient undergo further examination with cone beam computed tomography.
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The radiological images confirmed the initial diagnosis of CED. Marked enlargement and sclerotic imaging of the jaws were noted (Fig. 5,6) . As far as the maxilla was concerned, a torus palatinus was formed towards the posterior part of the hard palate in the midline (Fig. 7) and small exostoses arised bucally outward of the alveolar bone. A small exostosis arised bucally at the right side of the mandible. Possibly small tori mandibularis coexisted (Fig. 8) . No signs of osteonecrosis were noted; however, this was hard to estimate, due to the sclerotic pattern of the bone. The reduced mouth opening can be probably attributed to the significant enlargement of coronoid processes bilaterally, creating a physical restriction to mandibular mobility. (Fig. 9) We informed the patient of a possible surgical removal of the tori mentioned above, with special emphasis on the concomitant complications, as a result of the long-term use of bisphosphonates. We recommended she undergo conservative treatment with a six month follow-up observation. Discussion
The average age of the symptom onset is at the age of 14, but varies from birth until the age of 76. The sex incidence is equal, although it is noticeable that men appear with worse symptoms (6). There is no racial predisposition and the exact prevalence is unknown. Natural history is unpredictable, as there is great variability in the expression of clinical manifestations (7). 90% of patients complain of bone pain, principally at the lower limbs, which is constant, dull, deteriorated by exertion, stress and cold (8).Other symptoms are difficulty to walk, fatigue, muscle weakness and headache. (9), (10)
ACCEPTED MANUSCRIPT
SC
RI PT
Clinical examination reveals decreased muscle mass of upper and lower limbs, proximal muscle weakness and difficulty in standing up from a sitting position. 64% of patients obtain a wide-based, waddling gait, while 43% may have joint contractures. Scoliosis, lumbar lordosis , kyphosis , coxae or genua valga, flat feet can also coexist (5). The bones involved in decreasing order of frequency are femur, tibia, fibula, humerus,ulna and radius (11). Visual manifestations appear later and include blurred vision, papilledema, exophthalmos, even globe subluxation (12). Calvarial hyperostosis starts at the skull base, with consequent hearing or visual loss, facial nerve palsy, due to the encroachment of cranial nerves. It also appears at the frontal bone, as bossing. The mandible is sclerotic at 25% of patients and frequently enlarged. The dental eruption is normal, while the hyperostosis of the condyle and the coronoid process can induce reduced mobility (13). Facial and jaw alterations appear at severely infected individuals later in life. Systemic manifestations, such as anemia, leucopenia, hepatosplenomegaly, are rarely reported (14). Patients may have decreased incidence of fractures and osteoporosis, as a result of increased bone density. (6)
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M AN U
The diagnosis is based on clinical symptoms and radiological images. Patients can often be misdiagnosed for muscular dystrophy (15). Nevertheless, the disease should be considered, when a patient presents proximal muscle weakness, limb pain and waddling gait. Bone biopsy has non-typical findings, while the biochemical markers are usually within normal levels(6), (7). The typical radiological finding is hyperostosis of long bones, which is bilateral, symmetrical and usually starts at the diaphyses (2). Thickened cortices result from endosteal and periosteal bone formation. (16) Gradually the metaphyses can be involved, rarely the epiphyses and eventually the entire skeleton. Furthermore, the paranasal sinuses lose pneumatization, as they fill with bone. Despite the fact that radiological findings compatible with skull base sclerosis may appear at 50% of patients, less than 25% of them develop a cranial nerve dysfunction (17).
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Vanhoenacker et al. (2003), as well as Wallace et al. (2004) report that individuals, who carried the gene mutation and had no clinical symptoms, had positive radiological features. Bone scintigraphy can be used as a tool to estimate disease activity, but there are no sufficient data for its prognostic value (18). Tc-99m MDP uptake is positive in asymptomatic members of affected families and negative radiological findings. Nevertheless, bone scintigraphy can be normal in some relatives with positive radiological features. (19) Molecular analysis can provide additional information to establish a diagnosis. (16) Differential diagnosis includes van Buchem disease, which is autosomal recessive and manifests itself with mandibular enlargement and skull thickening. (6) Ribbing’s disease has radiographically similar features, but neuromuscular symptoms are milder and cranial nerve deficits are rare. (10) Craniodiaphyseal dysplasia, which is autosomal recessive, restricts to diaphyses and has milder cranial involvement. Chronic sclerosing osteomyelitis should also be excluded.
ACCEPTED MANUSCRIPT
RI PT
There are no published guidelines for CED management. Glucocorticoids, biosphosphonates, calcitonin, acetylsalicylic acid have been used. Glucocorticoids have an anti-inflammatory and immunosuppressive effect, inhibiting osteoblastic and inducing osteoclastic activity, preventing ossification (8). Controversial data exist in regard to clinical improvement of bone pain after treatment with biosphosphonates (18), (20). Recent reviews report clinical improvement after admission of losartan, an angiotensin II receptor antagonist for patients with Marfan syndrome, which is also characterized by hyperactive TGFΒ1 signaling. Losartan has been shown to inhibit TGFβ1 signaling, but its usage in CED needs further clinical research (3), (21). Conclusions
SC
Camurati Engelmann disease is a rare bone dysplasia, which can potentially affect the jaws. It can cause enlargement mainly of the mandible dimensions, reduced mouth opening and multiple exostoses.
M AN U
Conflict of interest None. Figures
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References
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Clinical view of the patient Reduced mouth opening Maxillary tori Torus palatinus 3D image of the maxilla as shown in CBCT 3D image of the mandible as shown in CBCT Torus palatinus as shown in CBCT Buccal exostosis at the right side of the mandible as shown in CBCT Enlargement of coronoid processes as shown in CBCT
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1. 2. 3. 4. 5. 6. 7. 8. 9.
1.Janssens K, Vanhoenacker F, Bonduelle M, Verbruggen L, Van Maldergem L, Ralston S, Guañabens N, Migone N, Wientroub S, Divizia MT, Bergmann C, Bennett C, Simsek S, Melançon S, Cundy T, Van Hul W : Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment. J Med Genet 43(1):1-11,Jan 2016
2. Bhadada SK, Sridhar S, Steenackers E, Dhiman V, Mortier G, Bhansali A, Van Hul W: Camurati-Engelmann disease (progressive diaphyseal dysplasia): reports of an Indian kindred. Calcif Tissue Int. 94(2):240-7, Feb 2014 3. Ayyavoo A, Derraik JG, Cutfield WS, Hofman PL:Elimination of pain
ACCEPTED MANUSCRIPT and improvement of exercise capacity in Camurati-Engelmann disease with losartan. J Clin Endocrinol Metab.99(11):3978-82,Nov 2014 4. Campos-Xavier B, Saraiva JM, Savarirayan R, Verloes A, Feingold J, Faivre L, Munnich A, Le Merrer M, Cormier-Daire V :Phenotypic variability at the TGF-beta1 locus in Camurati-Engelmann disease. Hum Genet 109(6):653-8,Dec 2001
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5. Wallace SE,Wilcox WR: Camurati-Engelmann disease. Gene Rev 25 June 2004
SC
6. Wallace SE, Lachman RS, Mekikian PB, Bui KK, Wilcox WR :Marked phenotypic variability in progressive diaphyseal dysplasia (CamuratiEngelmann disease): report of a four-generation pedigree, identification of a mutation in TGFB1, and review. Am J Med Genet A. 129A(3):235-47, Sep 2004
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7. Sparkes RS, Graham CB: Camurati-Engelmann disease. Genetics and clinical manifestations with a review of the literature. J Med Genet.9(1):73-85,Mar 1972 8. Mundra V, Taxel P: Camurati-Engelmann disease--a rare cause of bone pain. Conn Med 76(1):33-7,Jan 2012
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9. Ramon Y, Buchner A: Camurati-Engelmann's disease affecting the jaws. Oral Surg Oral Med Oral Pathol. 22(5):592-9,Nov 1966 10. Vanhoenacker FM, Janssens K, Van Hul W, Gershoni-Baruch R, Brik R, De Schepper AM. :Camurati-Engelmann disease. Review of radioclinical features. Acta Radiol. 44(4):430-4,Jul 2003
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11. Aggarwal P, Wali JP, Sharma SK: Progressive diaphyseal dysplasia: case report and literature review. Orthopedics.13(8):901-4,Aug 1990
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12. Alam T, Khurram M, Hamidi H, Khan AA:Visual and otologic manifestation of Camurati-Engelmann's disease: a case report. Radiol Case Rep.10(4):61-4,Oct 2015 13. Demas PN, Sotereanos GC: Facial-skeletal manifestations of Engelmann's disease. Oral Surg Oral Med Oral Pathol 68(6):686-90, Dec 1989 14. Crisp AJ, Brenton DP : Engelmann's disease of bone--a systemic disorder? Ann Rheum Dis.(2):183-8,Apr 1982 15. Plaiasu V, Costin A : Skeletal Dysplasia Presenting as a Neuromuscular Disorder - Report or a Family with CamuratiEngelmann Syndrome. Maedica (Buchar)10(1):48-51, Mar 2015 16. Bartuseviciene A, Samuilis A, Skucas J: Camurati-Engelmann disease: imaging, clinical features and differential diagnosis. Skeletal Radiol.
ACCEPTED MANUSCRIPT 38(11):1037-43,Nov 2009 17. Carlson ML, Beatty CW, Neff BA, Link MJ, Driscoll CL: Skull base manifestations of Camurati-Engelmann disease. Arch Otolaryngol Head Neck Surg 136(6):566-75, Jun 2010
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18. Castro GR, Appenzeller S, Marques-Neto JF, Bértolo MB, Samara AM, Coimbra I: Camurati-Engelmann disease: failure of response to bisphosphonates: report of two cases. Clin Rheumatol. 24(4):398401,Aug 2005
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19. Clybouw C, Desmyttere S, Bonduelle M, Piepsz A.: CamuratiEngelmann disease: contribution of bone scintigraphy to genetic counseling. Genet Couns.5(2):195-8, 1994
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20. Iba K, Takada J, Kamasaki H, Oda T, Hatakeyama N, Wada T, Yamashita T:Α significant improvement in lower limb pain after treatment with alendronate in two cases of Camurati-Engelmann disease. J Bone Miner Metab.26(1):107-9,Jan 2008
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21. Brooke BS, Habashi JP, Judge DP, Patel N, Loeys B, Dietz HC 3rd: Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. N Engl J Med. 358(26):2787-95,Jun 2008
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S0278-2391(17)30391-9
DOI:
10.1016/j.joms.2017.03.059
Reference:
YJOMS 57752
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 20 February 2017 Revised Date:
29 March 2017
Accepted Date: 31 March 2017
Please cite this article as: Fyrgiola M, Lianou V, Katoumas K, Dimopoulos I, A rare sporadic case of Camurati Engelmann disease with jaw involvement, Journal of Oral and Maxillofacial Surgery (2017), doi: 10.1016/j.joms.2017.03.059. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT A rare sporadic case of Camurati Engelmann disease with jaw involvement.
Fyrgiola Maria MD, DDS, Resident of the department of Oral and Maxillofacial
Athens, Greece Corresponding author contact information: Fyrgiola Maria
RI PT
Surgery, General Hospital “G. Gennimatas”, Mesogeion 154 Str., GR 11527,
Telephone (cell phone): +30-6974623681
M AN U
Telephone (home): +30- 2105023411
SC
Address (home): , Ikarias 11, GR 13231, Petroupoli, Athens, Greece
Fax (home): +30-
E-mail: [email protected] Co-authors
TE D
1. Violetta Lianou MD, DDS, MSc, PhD, Senior Registrar of the department of Oral and Maxillofacial Surgery, General Hospital “G.
EP
Gennimatas”, Mesogeion 154 Str., GR 11527, Athens, Greece
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2. Konstantinos Katoumas MD, DDS, MSc, PhD, Resident of the department of Oral and Maxillofacial Surgery, General Hospital “G. Gennimatas”, Mesogeion 154 Str., GR 11527, Athens, Greece
3. Ioannis Dimopoulos DDS, Head of the department of Oral and Maxillofacial Surgery, General Hospital “G. Gennimatas”, Mesogeion 154 Str., GR 11527, Athens, Greece
ACCEPTED MANUSCRIPT A rare sporadic case of Camurati Engelmann disease with jaw involvement. Maria Fyrgiola, Violeta Lianou, Konstantinos Katoumas, Ioannis Dimopoulos Department of Oral and Maxillofacial Surgery, Georgios Gennimatas General Hospital, 154 Mesogeion Str., Athens, GR 11527, Greece
Camurati-Engelmann disease Progressive diaphyseal dysplasia Tori Mandible enlargement
SC
Abstract
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Keywords
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Camurati-Engelmann disease (CED), or progressive diaphyseal dysplasia, is an uncommon bone dysplasia, which is inherited in an autosomal dominant pattern. The disease mainly affects the diaphyses of the long bones, but can also induce sclerotic changes to the facial skeleton and the skull base. The diagnosis of CED is based on clinical and radiological features. The purpose of the article is to present the clinical and radiological characteristics of the jaws, as shown in cone-beam computed tomography images of a 46-year old-female diagnosed with CED.
TE D
Introduction
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In 1922, Camurati first reported the disease, followed by Engelmann in 1929. Camurati-Engelmann disease, also known as progressive diaphyseal dysplasia, is a rare autosomal dominant disorder, resulting from mutations of the TGFβ1(transforming growth factor) gene (1). The responsible gene has been identified on chromosome 19q13. TGFβ1 plays a significant role in bone remodeling, stimulating bone formation and suppressing bone resorption under normal circumstances. (1), (2) Moreover, it suppresses myoblast maturation and adipogenesis and it impedes muscle reconstruction. (3) This condition typically results in cortical thickening of the diaphysis of the long bones and sclerotic alterations of the skull base (4). The diagnosis is challenging, due to lack of published guidelines. Approximately 306 cases have been reported so far (5). In our case we emphasize on the clinical and radiological manifestations of the facial skeleton in a female patient. Case Report In November 2015, a 46-year-old female was self-referred to the outpatient department of the oral and maxillofacial clinic, due to the presence of multiple firm nodules of the maxillary labial gingiva and of the hard palate. She reported that she had been diagnosed with CED since 2000 and has been under regular observation by a rheumatologist (Fig.1) .She had no other health problems. The patient has been treated with intravenous zoledronic
ACCEPTED MANUSCRIPT acid, prednisolone and alphacalcidol since diagnosis. During this time, she has developed presbyopia, hearing loss and walking abnormalities, progressive decrease in mouth opening and alterations of the external features of her face. None of her family’s members had similar symptoms, therefore we assumed she was a sporadic case.
M AN U
SC
RI PT
On physical examination the patient had an average height , a normal physical and mental growth, and difficulty in hearing and walking. Frontal bossing, bilateral exophthalmos and facial asymmetry without midline shift coexisted. The shape of the face was round, while the midface was normal. The mandible was enlarged, with increased height and width, particularly on the right side. The dental occlusion was Angle’s class II, division 2. The mouth opening was reduced (Fig. 2) .The dental eruption was normal and the maxillary first premolars had been extracted. There were maxillary tori, bilaterally, among maxillary lateral incisor and premolarand apically of the first molars (Fig.3) . A torus palatinus was noted at the midline of the hard palate (Fig.4) . We recommended the patient undergo further examination with cone beam computed tomography.
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EP
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The radiological images confirmed the initial diagnosis of CED. Marked enlargement and sclerotic imaging of the jaws were noted (Fig. 5,6) . As far as the maxilla was concerned, a torus palatinus was formed towards the posterior part of the hard palate in the midline (Fig. 7) and small exostoses arised bucally outward of the alveolar bone. A small exostosis arised bucally at the right side of the mandible. Possibly small tori mandibularis coexisted (Fig. 8) . No signs of osteonecrosis were noted; however, this was hard to estimate, due to the sclerotic pattern of the bone. The reduced mouth opening can be probably attributed to the significant enlargement of coronoid processes bilaterally, creating a physical restriction to mandibular mobility. (Fig. 9) We informed the patient of a possible surgical removal of the tori mentioned above, with special emphasis on the concomitant complications, as a result of the long-term use of bisphosphonates. We recommended she undergo conservative treatment with a six month follow-up observation. Discussion
The average age of the symptom onset is at the age of 14, but varies from birth until the age of 76. The sex incidence is equal, although it is noticeable that men appear with worse symptoms (6). There is no racial predisposition and the exact prevalence is unknown. Natural history is unpredictable, as there is great variability in the expression of clinical manifestations (7). 90% of patients complain of bone pain, principally at the lower limbs, which is constant, dull, deteriorated by exertion, stress and cold (8).Other symptoms are difficulty to walk, fatigue, muscle weakness and headache. (9), (10)
ACCEPTED MANUSCRIPT
SC
RI PT
Clinical examination reveals decreased muscle mass of upper and lower limbs, proximal muscle weakness and difficulty in standing up from a sitting position. 64% of patients obtain a wide-based, waddling gait, while 43% may have joint contractures. Scoliosis, lumbar lordosis , kyphosis , coxae or genua valga, flat feet can also coexist (5). The bones involved in decreasing order of frequency are femur, tibia, fibula, humerus,ulna and radius (11). Visual manifestations appear later and include blurred vision, papilledema, exophthalmos, even globe subluxation (12). Calvarial hyperostosis starts at the skull base, with consequent hearing or visual loss, facial nerve palsy, due to the encroachment of cranial nerves. It also appears at the frontal bone, as bossing. The mandible is sclerotic at 25% of patients and frequently enlarged. The dental eruption is normal, while the hyperostosis of the condyle and the coronoid process can induce reduced mobility (13). Facial and jaw alterations appear at severely infected individuals later in life. Systemic manifestations, such as anemia, leucopenia, hepatosplenomegaly, are rarely reported (14). Patients may have decreased incidence of fractures and osteoporosis, as a result of increased bone density. (6)
TE D
M AN U
The diagnosis is based on clinical symptoms and radiological images. Patients can often be misdiagnosed for muscular dystrophy (15). Nevertheless, the disease should be considered, when a patient presents proximal muscle weakness, limb pain and waddling gait. Bone biopsy has non-typical findings, while the biochemical markers are usually within normal levels(6), (7). The typical radiological finding is hyperostosis of long bones, which is bilateral, symmetrical and usually starts at the diaphyses (2). Thickened cortices result from endosteal and periosteal bone formation. (16) Gradually the metaphyses can be involved, rarely the epiphyses and eventually the entire skeleton. Furthermore, the paranasal sinuses lose pneumatization, as they fill with bone. Despite the fact that radiological findings compatible with skull base sclerosis may appear at 50% of patients, less than 25% of them develop a cranial nerve dysfunction (17).
AC C
EP
Vanhoenacker et al. (2003), as well as Wallace et al. (2004) report that individuals, who carried the gene mutation and had no clinical symptoms, had positive radiological features. Bone scintigraphy can be used as a tool to estimate disease activity, but there are no sufficient data for its prognostic value (18). Tc-99m MDP uptake is positive in asymptomatic members of affected families and negative radiological findings. Nevertheless, bone scintigraphy can be normal in some relatives with positive radiological features. (19) Molecular analysis can provide additional information to establish a diagnosis. (16) Differential diagnosis includes van Buchem disease, which is autosomal recessive and manifests itself with mandibular enlargement and skull thickening. (6) Ribbing’s disease has radiographically similar features, but neuromuscular symptoms are milder and cranial nerve deficits are rare. (10) Craniodiaphyseal dysplasia, which is autosomal recessive, restricts to diaphyses and has milder cranial involvement. Chronic sclerosing osteomyelitis should also be excluded.
ACCEPTED MANUSCRIPT
RI PT
There are no published guidelines for CED management. Glucocorticoids, biosphosphonates, calcitonin, acetylsalicylic acid have been used. Glucocorticoids have an anti-inflammatory and immunosuppressive effect, inhibiting osteoblastic and inducing osteoclastic activity, preventing ossification (8). Controversial data exist in regard to clinical improvement of bone pain after treatment with biosphosphonates (18), (20). Recent reviews report clinical improvement after admission of losartan, an angiotensin II receptor antagonist for patients with Marfan syndrome, which is also characterized by hyperactive TGFΒ1 signaling. Losartan has been shown to inhibit TGFβ1 signaling, but its usage in CED needs further clinical research (3), (21). Conclusions
SC
Camurati Engelmann disease is a rare bone dysplasia, which can potentially affect the jaws. It can cause enlargement mainly of the mandible dimensions, reduced mouth opening and multiple exostoses.
M AN U
Conflict of interest None. Figures
AC C
References
TE D
Clinical view of the patient Reduced mouth opening Maxillary tori Torus palatinus 3D image of the maxilla as shown in CBCT 3D image of the mandible as shown in CBCT Torus palatinus as shown in CBCT Buccal exostosis at the right side of the mandible as shown in CBCT Enlargement of coronoid processes as shown in CBCT
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1. 2. 3. 4. 5. 6. 7. 8. 9.
1.Janssens K, Vanhoenacker F, Bonduelle M, Verbruggen L, Van Maldergem L, Ralston S, Guañabens N, Migone N, Wientroub S, Divizia MT, Bergmann C, Bennett C, Simsek S, Melançon S, Cundy T, Van Hul W : Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment. J Med Genet 43(1):1-11,Jan 2016
2. Bhadada SK, Sridhar S, Steenackers E, Dhiman V, Mortier G, Bhansali A, Van Hul W: Camurati-Engelmann disease (progressive diaphyseal dysplasia): reports of an Indian kindred. Calcif Tissue Int. 94(2):240-7, Feb 2014 3. Ayyavoo A, Derraik JG, Cutfield WS, Hofman PL:Elimination of pain
ACCEPTED MANUSCRIPT and improvement of exercise capacity in Camurati-Engelmann disease with losartan. J Clin Endocrinol Metab.99(11):3978-82,Nov 2014 4. Campos-Xavier B, Saraiva JM, Savarirayan R, Verloes A, Feingold J, Faivre L, Munnich A, Le Merrer M, Cormier-Daire V :Phenotypic variability at the TGF-beta1 locus in Camurati-Engelmann disease. Hum Genet 109(6):653-8,Dec 2001
RI PT
5. Wallace SE,Wilcox WR: Camurati-Engelmann disease. Gene Rev 25 June 2004
SC
6. Wallace SE, Lachman RS, Mekikian PB, Bui KK, Wilcox WR :Marked phenotypic variability in progressive diaphyseal dysplasia (CamuratiEngelmann disease): report of a four-generation pedigree, identification of a mutation in TGFB1, and review. Am J Med Genet A. 129A(3):235-47, Sep 2004
M AN U
7. Sparkes RS, Graham CB: Camurati-Engelmann disease. Genetics and clinical manifestations with a review of the literature. J Med Genet.9(1):73-85,Mar 1972 8. Mundra V, Taxel P: Camurati-Engelmann disease--a rare cause of bone pain. Conn Med 76(1):33-7,Jan 2012
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9. Ramon Y, Buchner A: Camurati-Engelmann's disease affecting the jaws. Oral Surg Oral Med Oral Pathol. 22(5):592-9,Nov 1966 10. Vanhoenacker FM, Janssens K, Van Hul W, Gershoni-Baruch R, Brik R, De Schepper AM. :Camurati-Engelmann disease. Review of radioclinical features. Acta Radiol. 44(4):430-4,Jul 2003
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