0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Article |

Skull Base Manifestations of Camurati-Engelmann Disease FREE

Matthew L. Carlson, MD; Charles W. Beatty, MD; Brian A. Neff, MD; Michael J. Link, MD; Colin L. W. Driscoll, MD
[+] Author Affiliations

Author Contributions: Departments of Otolaryngology–Head and Neck Surgery (Drs Carlson, Beatty, Neff, Link, and Driscoll) and Neurologic Surgery (Drs Link and Driscoll), Mayo Clinic School of Medicine, Rochester, Minnesota.


Arch Otolaryngol Head Neck Surg. 2010;136(6):566-575. doi:10.1001/archoto.2010.68.
Text Size: A A A
Published online

Objective  To describe presenting symptoms, evaluation findings, and surgical management of cranial base hyperostosis in patients with Camurati-Engelmann disease (CED).

Design  Retrospective study and literature review.

Setting  The Mayo Clinic, Rochester, Minnesota.

Patients  A total of 306 patients diagnosed as having CED, including 12 primarily evaluated at our institution between 1968 and 2008, and 294 identified in the international literature.

Main Outcome Measures  Presenting symptoms, methods of diagnosis, treatment strategies, and patient outcomes.

Results  One hundred seventy-three of 306 patients (56.5%) had radiographically proven skull base hyperostosis, whereas less than one-fourth were symptomatic. The most common manifestations of cranial base involvement were hearing loss (19.0%), headache (10.4%), exophthalmos (8.2%), and frontal bossing (7.2%); less common were vision changes, vertigo, facial weakness, symptomatic brainstem compression, facial numbness, and hyposmia. Although corticosteroids and bisphosphates may treat torso and extremity involvement, they demonstrate no benefit for symptomatic skull base disease. In select symptomatic patients, aggressive decompression surgery may provide the only means of treatment. Decompression surgery is more challenging with thick sclerotic bone, loss or obscuration of bony landmarks, and decreased supratentorial space. Patients must be counseled on the increased risks associated with surgery and the potential for redeposition of bone and recurrence of symptoms.

Conclusions  Physicians should include CED in the differential diagnosis for patients with radiographic evidence of skull base thickening and synchronous cranial neuropathies or symptoms of elevated intracranial pressure. In mild forms of the disease, the clinical course of patients should be followed with serial examination, audiometric testing, and radiography. In select patients with progressive cranial base symptoms, aggressive wide decompression of involved neurovascular structures may provide benefit.

Figures in this Article

Camurati-Engelmann disease (CED), also known as progressive diaphyseal dysplasia, is a rare autosomal dominant disorder characterized by progressive symmetric diaphyseal sclerosis of the long bones and potential cranial hyperostosis. Camurati-Engelmann disease belongs to the larger class of craniotubular bone disorders that include osteopetrosis, craniodiaphyseal dysplasia, and van Buchem disease.1 Since its first report in 1920 by Cockayne2 and later descriptions by Camurati3 and subsequently Engelmann,4 we identified a total of 306 cases published in the international literature.

The gene linked to the development of CED codes for the β1 subunit of transforming growth factor (TGFB1; OMIM 190180)57 was isolated to chromosome 19q in 2000.8,9 Mutations of this gene result in increased transforming growth factor activity5,10 and subsequent stimulation of osteoblastic bone formation and suppression of osteoclastic resorption.11

Presenting symptoms commonly include musculoskeletal complaints of lower limb weakness, muscle pain, and gait unsteadiness,12 whereas cranial base manifestations occur in less than a quarter of patients. The mandible is sclerotic in approximately 25% of patients and infrequently may be enlarged.1315 Symptomatic cranial base involvement is variable and is caused by bony overgrowth of the skull base, leading to foraminal stenosis and diminished cranial vault volume resulting in neurovascular compromise and potentially increased intracranial pressure (ICP), respectively.1619

After institutional review board approval, we performed a retrospective review from 1968 through 2008 using the electronic medical record, and all patients diagnosed as having CED were included. Data were collected with respect to age, sex, presenting symptoms, evaluation, imaging, surgical management, and treatment outcomes. In addition, a literature review dating back to the first reported case in 19202 was performed to calculate the prevalence and characteristics of presenting symptoms, treatment outcomes, and associated skull base findings.

In the past 40 years, a total of 12 patients (4 male and 8 female) with the diagnosis of CED underwent evaluation and treatment at the Mayo Clinic. Of these, 8 (67%) were found to have radiographic evidence of skull base thickening and concurrent cranial base signs and symptoms of disease (Table 1). The average age at onset of symptomatic cranial base involvement was 24 (range, 15-35) years.

Table Graphic Jump LocationTable 1. Demographic Data, Findings, and Surgical Treatments in Patients Diagnosed as Having CED-Associated Skull Base Involvement
INITIAL PRESENTATION OF DISEASE

The mean age of first symptom onset was 8.7 (range, 1.5-30) years, with 11 of 12 patients initially reporting lower extremity pain, 9 describing gait unsteadiness or ataxia, and 2 complaining of lower extremity weakness. In addition to pain and gait instability, patient 3 experienced a pathologic fracture of his left tibia at 4 years of age, which led to the diagnosis of CED, and patient 8 required extensive spinal fusion surgery at 19 years of age for severe scoliosis. Two unrelated patients (3 and 5) experienced rapid growth in their later teenage years, one of whom required epiphysiodesis to remedy her uncontrolled lower extremity growth and pain. Both patients underwent additional molecular diagnostic testing and were found to have a heterogeneous missense mutation (c.652C→T [R218C]) of the TGFB1 gene. Nine of 12 patients had a known family history of disease, whereas 3 cases appeared to be sporadic.

OPHTHALMOPATHY, HEADACHE, AND BRAINSTEM INVOLVEMENT

Four patients (mean age, 29 years) developed progressive bilateral symmetric exophthalmia (Figure 1A and B), 3 of whom were asymptomatic without optic neuropathy. The fourth (patient 2) experienced deteriorating visual acuity. All 4 patients had radiographic anterior cranial floor thickening and shallow orbits, and 3 of 4 demonstrated considerable frontal bossing.

Place holder to copy figure label and caption
Figure 1.

Clinical findings in patient 5 (Table 1) with Camurati-Engelmann disease. Bilateral exophthalmia (A), square jaw line and frontal bossing (B), bony overgrowth of the mandible (C), and thickened craniotomy bone plate during a middle fossa approach (D) are demonstrated.

Graphic Jump Location

At 14 years of age, patient 2 underwent evaluation for increased headaches, blurred vision, and papilledema. During lumbar puncture she was found to have an elevated opening pressure of 35 cm H2O. Skull base radiography demonstrated diffuse bony thickening. At 30 years of age (1976), after worsening headaches and deteriorating vision, she underwent a right subtemporal decompression with postoperative improvement of her neurological symptoms. She is now 63 years of age and has not had a recurrence of visual symptoms or headache.

Patient 6 experienced headache and vision changes in the absence of exophthalmia or radiographic anterior cranial fossa involvement. Early in the third decade of life, he developed worsening dysphagia to solids and liquids, vision changes, and intermittent debilitating headaches exacerbated by Valsalva maneuvers. Plain radiographs of the skull base demonstrated a stenotic heart-shaped foramen magnum, and magnetic resonance imaging found an Arnold-Chiari malformation. At 41 years of age (2001), he underwent a suboccipital craniectomy with C1 laminectomy, which completely resolved his headaches, visual symptoms, and dysphagia without recurrence.

Four other patients experienced headaches but, in contrast to patients 2 and 6, they did not report vision changes or other overt symptoms of increased ICP or brainstem compression.

AUDIOVESTIBULAR AND FACIAL NERVE INVOLVEMENT

A total of 6 patients were diagnosed as having hearing loss (4 bilateral and 2 unilateral), 3 of whom reported concurrent dizziness, while none demonstrated facial nerve weakness or spasm. All 6 patients with hearing loss had pure sensorineural deficits most commonly affecting the higher frequencies, and no patients were found to have mixed or conductive losses. Patients 2, 5, and 8 underwent surgical intervention for progressive internal auditory canal (IAC) stenosis, whereas patients 3, 6, and 7 were conservatively observed with no worsening of symptoms.

By 40 years of age, patient 2 experienced deteriorating hearing and balance without facial nerve weakness. Further testing revealed a hypofunctioning right labyrinth and bilateral moderate sloping to profound sensorineural hearing loss (SNHL). Computed tomography of the head and temporal bones demonstrated significant skull base thickening with bilateral IAC stenosis. In 1987, she subsequently underwent a right retrosigmoid craniotomy with IAC decompression. Postoperatively she experienced profound right-sided SNHL and complete facial paralysis requiring right lateral tarsorrhaphy. Her balance and vision remained stable, and hearing in the left ear (which did not undergo surgery) continued to deteriorate.

By the middle of the fourth decade of life, patient 5 noted subjective hearing loss, and an audiogram found symmetric bilateral high-frequency SNHL. Computed tomography of the temporal bone confirmed the presence of severe narrowing of her IACs bilaterally (Figure 2A and B). She denied any vertiginous symptoms but felt generally unsteady; results of vestibular testing were within normal limits. Given her worsening hearing, considerable bilateral IAC stenosis, and family history of aggressive phenotypic disease, at 42 years of age she elected to proceed with staged bilateral middle fossa IAC decompressions in 2008 and 2009 (Figure 2C and D). During the year since surgery, she demonstrated no deterioration of hearing.

Place holder to copy figure label and caption
Figure 2.

Preoperative and postoperative computed tomographic (CT) images in patient 5 (see Table 1) with Camurati-Engelmann disease. Preoperative left-sided coronal (A) and axial (B) high-resolution CT images of the temporal bone demonstrating bony overgrowth of the internal auditory canal (arrows). Postoperative coronal (C) and axial (D) CT images of the left temporal bone demonstrating interval decompression of the facial and vestibulocochlear nerve complex (arrows) through a middle fossa craniotomy.

Graphic Jump Location

During the fifth decade of life, patient 8 experienced increasing bilateral high-pitched tinnitus, vertigo, and bilateral hearing loss. Electronystagmography demonstrated bilateral vestibular hypofunction, and audiometric evaluation found profound bilateral SNHL. At 58 years of age (2001), he underwent a planned 2-stage procedure that included middle fossa decompression of his right IAC and subsequent cochlear implantation 2 months later. He was observed for 6 years after the initial implantation and continued to derive benefit from his device. Soon thereafter, he died of unrelated pulmonary disease.

Patient 3 developed progressive hearing loss and tinnitus spanning a 15-year period starting in the middle of the third decade of life. An audiogram demonstrated normal hearing in the right ear and mild sloping to moderate downsloping SNHL in the left ear. He denied symptoms of dizziness. At 38 years of age, his hearing had remained stable and he had not undergone any surgical intervention.

During his adolescent years, patient 6 developed mild bilateral hearing loss and high-pitched tinnitus without vestibulopathy or facial nerve weakness. Plain radiographs of the skull base demonstrated sclerotic petrous ridges. Despite radiographic evidence of lateral skull base involvement, his audiovestibular symptoms remained stable. At 49 years of age, he showed no further deterioration.

By 38 years of age, patient 7 reported significant right-sided hearing loss, dizziness, and high-frequency tinnitus. Audiometric evaluation demonstrated mild right-sided high-frequency SNHL. Results of subsequent vestibular testing were within normal limits. Given her mild unilateral symptoms, no surgical interventions were pursued. At 48 years of age, she had stable audiovestibular symptoms and had not required surgical decompression.

MEDICAL MANAGEMENT

Eleven of 12 patients were medically treated for chronic lower extremity pain. Of these, only 2 found relief with nonsteroidal anti-inflammatory drugs, 6 improved with the addition of prednisone therapy, and 1 required a combination of nonsteroidal anti-inflammatory drugs, corticosteroids, and narcotic pain medications. Two patients experienced chronic refractory pain and underwent a trial of bisphosphonate treatment with no additional perceived benefit. Despite any reported improvements in lower extremity pain, corticosteroid and bisphosphonate therapy did not improve headache or other neurological symptoms in any patients with skull base involvement.

During the past 30 years, we have examined a total of 12 patients who were ultimately diagnosed as having CED, 8 of whom were found to have symptomatic skull base involvement (Table 1). We performed a review of the literature dating back to the first account with Cockayne2 in 1920 and, including the present 12 patients, there have been a total of 306 unique cases of CED. The average age at the onset of symptoms was 13.4 years, with 45.7% of patients being male and 54.3% female. Documented radiographic skull base involvement was described in 173 patients (56.5%). The most common skull base symptoms included hearing loss, headaches, frontal bossing, and ophthalmopathy (Table 2). Many of the published cases did not specifically focus on skull base or neurological disease and therefore may have left out certain details; as a result, we acknowledge that our review of the literature may underreport associated signs and symptoms of skull base involvement.

Table Graphic Jump LocationTable 2. Prevalence of Skull Base Manifestations Among 306 Published Cases
DIAGNOSIS AND RADIOGRAPHIC FINDINGS

The symptoms and physical manifestations of CED are extremely variable even among affected kindred.7,20 Only 74% of patients with TGFB1 mutations express clinical symptoms, whereas radiographic abnormalities are found in approximately 94% of patients.12 Multiple reports in the literature describe asymptomatic patients who were diagnosed as having CED after incidental radiographic findings21,22 or molecular testing.23 Owing to the phenotypic variability and incomplete penetrance, establishing sensitive clinical criteria has proven difficult.7,12 Among reports, a large variety of diagnostic and prognostic tools have been described in the evaluation of CED. Radiography and genomic mutational analysis have proven highly sensitive, whereas other investigatory strategies that include biopsy,2426 peripheral blood smear, erythrocyte sedimentation rate, and measurement of serum calcium, phosphorus, and alkaline phosphatase levels have been met with less success.23

Radiographic screening with plain x-rays and computed tomography is a sensitive diagnostic tool and provides valuable information for making the initial diagnoses and establishing the extent of involvement. Bone scintigraphy has been shown to complement standard radiographic evaluation when determining disease activity and progression.27 The hallmark of CED is progressive symmetric diaphyseal hyperostosis of the lower extremities and is found in 94% to 98% of patients.12,23 Skull base involvement has been estimated to occur in more than half of all patients12 and, in our review, cranial base sclerosis occurred in 173 of 306 published cases (56.5%).

The defining characteristics and differential diagnosis of CED are well described in previous publications.1,20,28,29 There are multiple sclerosing bone disorders in patients with normal stature that commonly affect the skull base. Van Buchem disease (generalized cortical hyperostosis) is a rare autosomal recessive disease characterized by sclerosis of the skull, mandible, and clavicles. A common, striking feature is a large overbearing mandible, and, rarely, the circumference of the skull is enlarged. Craniodiaphyseal dysplasia can be distinguished with characteristic massive facial bone enlargement, hypertelorism, paranasal bossing, and nasal flattening.1 Ribbing disease is often viewed as a milder variant of CED; in contrast, Ribbing disease affects the skeletal system in an asymmetric manner.30,31

Genetic screening may be helpful, particularly in cases of no known family history of CED (≤30% of cases are sporadic) or when symptoms are subtle and results of diagnostic tests are inconclusive. In their report, Janssens and colleagues12 reviewed 100 cases from 24 separate families and found mutations in the gene coding for TGFB1 in virtually all symptomatic patients.

SKULL BASE MANIFESTATIONS AND MANAGEMENT

Although more than 50% of patients with CED will have radiographically confirmed skull base involvement, less than 25% experience cranial nerve dysfunction. Owing to the symmetric but often irregular cranial base involvement,29 the laterality and progression of individual cranial neuropathies are unpredictable. Some patients may note abrupt unilateral hearing loss, facial nerve paralysis, or vision loss; others may experience gradual or fluctuating unilateral or bilateral symptoms.16,32 Hyperostosis is 2 to 3 times more common in the anterior and middle fossa compared with the posterior fossa.29 Cranial neuropathies are thought to result from foraminal narrowing or increased ICP.18,19,33 Generalized vasculopathy occurs in many patients, resulting in thickening of vessel walls,13,3438,175 which may further compromise tenuous vascular flow through already stenotic bony canals.

Given the rarity of CED, there are currently no randomized controlled trials documenting pharmacologic effectiveness of corticosteroid or bisphosphonate therapy. Multiple isolated reports document improvement in lower extremity gait coordination, muscle pain, exercise tolerance, and appetite after corticosteroid administration.14,21,3949,176 Radiographic and histological reversal of disease has been described in select cases,40,42,46,48 whereas others report no such improvements.49 Bisphosphonate therapy has been met with less success; few reports document improvement,50 whereas most report no change51,52 or detrimental effects.46 Medical therapy, including corticosteroids and bisphosphonates, does not appear to benefit cranial base disease progression or symptoms.18,42,43,45,53

The primary management of progressive symptomatic skull base involvement remains surgical decompression in carefully selected patients. Surgery is technically demanding, with sclerotic bony changes,18,177 decreased pneumatization of paranasal sinuses,15,18,29 reduced space for supratentorial access,53 and potential obscuration or loss of critical landmarks.16,5355 Patients should be counseled on the increased risks associated with surgery,17,18,56,57 and additional measures such as intraoperative image guidance should be considered particularly for cranial nerve decompression. Cranial base manifestations of disease are mainly caused by foraminal stenosis and increased ICP; as such, interventions addressing both conditions are met with the most success.17,19 Bony regrowth after decompression remains a concern. In our literature review, 3 of 28 decompression procedures had radiographically proven bony regrowth.16,23,54,58

Temporal bone involvement may result in cochleovestibulopathy and facial nerve weakness. In our review of 306 cases, hearing loss was the most commonly cited cranial base symptom and occurred in 58 of 306 patients (19.0%).12,1419,23,24,3033,35,38,41,53,5578 In a 1996 review, Higashi and Matsuki67 found a similar rate of 17.7% (23 of 130). Hearing loss can be conductive, caused by external auditory canal stenosis,18,35,65 ossicular56 or stapes fixation,73,78 chronic effusion secondary to eustachian tube narrowing and dysfunction,63,67,76 overgrowth of the round or oval window,53 and cholesteatoma formation.63 Sensorineural hearing loss may result from otic capsule involvement56,78 or IAC neurocompression, and mixed hearing loss can occur from a combination of these factors. The type of hearing loss was documented in 34 of the 58 cases (64.7% SNHL, 11.8% conductive hearing loss, and 23.5% mixed hearing loss). Gait unsteadiness is a frequently encountered symptom, whereas vertigo was found in only 13 of 306 patients (4.2%).16,30,53,55,63,70,77,78 Similar to many patients with SNHL, vertigo is most likely related to neurovascular compression from critical IAC stenosis.53,55 Facial nerve weakness or spasm is the most common motor cranial neuropathy and has been documented in 13 cases (4.2%).12,15,17,18,23,31,32,35,57,62,64,69 Less commonly, trigeminal neuropathy occurs, manifesting as facial numbness with or without masticatory weakness.17,71

Treatment of hearing loss requires a keen understanding of the disease process and potential sites of involvement.78 Conductive hearing loss may be managed by conventional hearing aid amplification,56,57 bone-anchored hearing devices,56 stapedectomy,78 or ventilation tube insertion,76 depending on the underlying cause. Those with early or mild SNHL and radiographic IAC stenosis may initially benefit from conventional hearing aids57 but should consider middle fossa79 or retrosigmoid55 IAC decompression with the goal of longer-term hearing preservation. Those with advanced SNHL may benefit from cochlear implantation with79 or without57 IAC decompression, depending on the degree of IAC stenosis. Current knowledge dictates that critical IAC stenosis is a contraindication to cochlear implantation178; however, we have found that staged cochlear implantation after adequate IAC decompression is beneficial for hearing restoration in patients with CED.79

Internal auditory canal decompression in CED is technically demanding given the sclerotic nature of the bone and obscuration of normal surgical landmarks. Including patients in the present series, we identified a total of 14 IAC decompressions (in 11 patients) performed for hearing loss, vestibular symptoms, or facial nerve weakness16,17,23,32,35,53,55,57; 3 of these reported iatrogenic injuries to the facial or cochleovestibular nerve complex,17,57 8 demonstrated lasting hearing improvement or stabilization,16,32,53,55 and 3 were met with initial hearing stabilization followed by eventual hearing decline and recurrence of symptoms.16,23 Two reports discuss isolated 8- and 15-dB high-frequency SNHL after successful IAC decompression for vestibular symptoms; they implicate acoustic trauma or heat injury associated with prolonged drilling with a diamond burr.53,55

The progression of facial nerve involvement is unpredictable.16,32 It has been hypothesized that those with an intermittent progressive course may be afflicted by repeated acute viral inflammation resulting in neural edema and arterial tamponade, as in Bell’s palsy.16,179 Those with a more indolent course may have progressive venous congestion associated with foraminal overgrowth, resulting in edema and subsequent arterial occlusion.16 Although there are multiple reports of successful facial nerve decompressions in other skull base hyperostotic syndromes,32,179,180 only 4 patients with CED underwent decompression for facial nerve weakness or spasm.16,17,32,57 Two of these documented long-term success, attributing favorable outcomes to extensive IAC and fallopian canal decompression.16,32 Given the potential for multilevel involvement, full facial canal (or, at a minimum, IAC and labyrinthine segment) decompression is advocated.32,53,179

Ophthalmopathy occurred in less then 10% of patients and included exophthalmos,28,30,33 papilledema,23,24,38,54,58,60,62,75,76,8083 and optic nerve atrophy.30,33,54,60,84 Ocular changes are attributed to bony overgrowth of the orbit, optic canal stenosis, and increased ICP.62 Anterior fossa involvement commonly manifests with frontal bossing and exophthalmos,29 and hyposmia has been reported in 1 patient.23 Most patients with globe protrusion are asymptomatic, but a small percentage may experience diplopia and, in extreme circumstances, globe subluxation.85 Early reports had attributed vision loss and blindness to optic nerve compression, and surgical management primarily involved optic nerve sheath fenestration and narrow field optic nerve or orbital decompression; however, such strategies were met with only limited success.54,58,60,62 Growing evidence suggests that ophthalmologic deterioration is caused by the effects of optic nerve compression and increased ICP; only after aggressive broad cranial decompression (usually through a subtemporal craniotomy) and restoration of normal ICP are orbital symptoms consistently improved.19,54,76,81,82

Increased ICP is thought to result from diminished intracranial volume from diffuse bony overgrowth and jugular foramen stenosis, resulting in compromised internal jugular venous outflow.17,76 The true incidence of elevated ICP in CED is unknown because only symptomatic patients may undergo lumber puncture.19,62 Presentation is variable and may include headache28 (10%), vision changes74 (4%), papilledema (3%), and other cranial neuropathies. Associated gait changes may be difficult to appreciate given that most patients demonstrate lower extremity weakness and muscle pain as presenting symptoms independent of skull base involvement.12

Including 1 patient from this report, a total of 5 patients with CED had symptomatic brainstem herniation.18,19,81,82 The exact mechanism is unclear but is theorized to result from caudal displacement of the brainstem due to progressive intracranial volume loss combined with elevated ICP.18,19,81,82 All 5 patients experienced severe headaches and vision changes, 4 had progressive imbalance,18,19,81 and 2 experienced dysphagia.18 There has been only 1 report of dysphagia and diminished gag reflex outside those with symptomatic brainstem compression.17 Jugular foramen syndromes manifesting with compression of cranial nerves IX, X, and XI have not been associated with CED; we suspect this is because of the infrequent involvement of the posterior fossa29 and the relatively large diameter of the jugular foramen.

Acetazolamide therapy,19,62,82 therapeutic lumbar puncture,19,62 and ventriculoperitoneal shunting55,81 have been used for temporary management, but most patients eventually require decompressive craniotomies. Isolated suboccipital craniectomy procedures have been met with mixed success, and 1 case documents intraoperative death.18 It is generally recommended that patients with increased ICP with or without brainstem herniation undergo broad decompressive craniectomies to improve or restore cranial vault space.81,82

RECOMMENDATIONS FOR FOLLOW-UP

The management of cranial base involvement requires multidisciplinary surveillance and treatment. On diagnosis, those with CED should undergo screening radiographic bone surveys, and all patients with skull base involvement should have baseline computed tomography of the head and neck to confirm the presence and extent of disease. Since more than half of all patients with skull base hyperostosis are asymptomatic, and because there may be disconcordance between the degree of sclerosis and symptoms, only patients who are symptomatic require further imaging.

Surveillance in patients with asymptomatic skull base involvement should include annual ophthalmologic, otolaryngologic, and neurological examinations. Eye examination should evaluate for proptosis, exposure keratitis, papilledema, and loss of visual acuity; evaluation by the otolaryngologist may provide insight into cranial neuropathies and audiovestibular abnormalities; neurological assessment should emphasize cranial nerve involvement but also evaluate for signs of increased ICP and brainstem herniation. More rigorous monitoring is required for those with progressive symptomatic disease who would consider surgical intervention because earlier decompression may result in more favorable outcomes.

Camurati-Engelmann disease is a rare disease that results in symptomatic cranial base hyperostosis in less than one-fourth of patients. Hearing loss and headache are the most frequent findings, whereas ophthalmopathy, facial nerve weakness, brainstem herniation, and trigeminal neuropathies are less common. In asymptomatic and mild forms of disease, patients should be followed up with serial examination, audiometric testing, and imaging.

Unfortunately, there remains no known pharmacologic or surgical strategy for disease reversal. In contrast to lower extremity disease progression, medical therapy has not been successful in treating associated skull base symptoms. Surgery with aggressive wide bony decompression is technically challenging but remains the only option for patients with advanced disease.

Correspondence: Colin L. W. Driscoll, MD, Department of Otorhinolaryngology–Head and Neck Surgery, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (driscoll.colin@mayo.edu).

Submitted for Publication: October 19, 2009; final revision received November 19, 2009; accepted January 13, 2010.

Author Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Carlson, Beatty, Link, and Driscoll. Acquisition of data: Carlson and Driscoll. Analysis and interpretation of data: Carlson, Beatty, and Neff. Drafting of the manuscript: Carlson, Neff, and Driscoll. Critical revision of the manuscript for important intellectual content: Carlson, Beatty, Link, and Driscoll. Study supervision: Carlson, Beatty, Neff, Link, and Driscoll.

Financial Disclosure: None reported.

Gorlin  RCohen  MHennekam  RSyndromes of the Head and Neck. 4th ed. New York, NY Oxford University Press2001;
Cockayne  E Case for diagnosis. Proc R Soc Med 1920;13132- 136
PubMed
Camurati  M Di un raro caso di osteite simmetrica ereditaria degli arti inferiori. Chir Organi Mov 1922;6662- 665
Engelmann  G Ein Fall von Osteopathia hyperostotica multiplex infantilis. Fortschr Geb Rontgenstr Nuklearmed 1929;391101- 1106
Janssens  Kten Dijke  PRalston  SHBergmann  CVan Hul  W Transforming growth factor-β1 mutations in Camurati-Engelmann disease lead to increased signaling by altering either activation or secretion of the mutant protein. J Biol Chem 2003;278 (9) 7718- 7724
PubMed
Kinoshita  ASaito  TTomita  H  et al.  Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease. Nat Genet 2000;26 (1) 19- 20
PubMed
Campos-Xavier  BSaraiva  JMSavarirayan  R  et al.  Phenotypic variability at the TGF-β1 locus in Camurati-Engelmann disease. Hum Genet 2001;109 (6) 653- 658
PubMed
Ghadami  MMakita  YYoshida  K  et al.  Genetic mapping of the Camurati-Engelmann disease locus to chromosome 19q13.1-q13.3. Am J Hum Genet 2000;66 (1) 143- 147
PubMed
Janssens  KGershoni-Baruch  RVan Hul  E  et al.  Localisation of the gene causing diaphyseal dysplasia Camurati-Engelmann to chromosome 19q13. J Med Genet 2000;37 (4) 245- 249
PubMed
Saito  TKinoshita  AYoshiura  K-i  et al.  Domain-specific mutations of a transforming growth factor (TGF)-β1 latency-associated peptide cause Camurati-Engelmann disease because of the formation of a constitutively active form of TGF-β1. J Biol Chem 2001;276 (15) 11469- 11472
PubMed
Janssens  Kten Dijke  PJanssens  SVan Hul  W Transforming growth factor-β1 to the bone. Endocr Rev 2005;26 (6) 743- 774
PubMed
Janssens  KVanhoenacker  FBonduelle  M  et al.  Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment. J Med Genet 2006;43 (1) 1- 11
PubMed
Ramon  YBuchner  A Camurati-Engelmann's disease affecting the jaws. Oral Surg Oral Med Oral Pathol 1966;22 (5) 592- 599
PubMed
Crisp  AJBrenton  DP Engelmann's disease of bone: a systemic disorder? Ann Rheum Dis 1982;41 (2) 183- 188
PubMed
Demas  PNSotereanos  GC Facial-skeletal manifestations of Engelmann's disease. Oral Surg Oral Med Oral Pathol 1989;68 (6) 686- 690
PubMed
Miyamoto  RTHouse  WFBrackmann  DE Neurotologic manifestations of the osteopetroses. Arch Otolaryngol 1980;106 (4) 210- 214
PubMed
Applegate  LJApplegate  GRKemp  SS MR of multiple cranial neuropathies in a patient with camurati-engelmann disease: case report. AJNR Am J Neuroradiol 1991;12 (3) 557- 559
PubMed
Simpson  RK  JrFischer  DKGall  GKRose  JE Fatal cerebellar herniation secondary to Camurati-Englemann's disease. J Neurol Neurosurg Psychiatry 1988;51 (10) 1349- 1352
PubMed
van Dalsem  VFGenant  HKNewton  TH Progressive diaphyseal dysplasia: report of a case with thirty-four years of progressive disease. J Bone Joint Surg Am 1979;61 (4) 596- 598
PubMed
Saraiva  JM Progressive diaphyseal dysplasia: a three-generation family with markedly variable expressivity. Am J Med Genet 1997;71 (3) 348- 352
PubMed
Low  LCStephenson  JBStuart-Smith  DA Progressive diaphyseal dysplasia mimicking childhood myopathy: clinical and biochemical response to prednisolone. Aust Paediatr J 1985;21 (3) 193- 196
PubMed
Girdany  B Engelmann's disease (progressive diaphyseal dysplasia): a nonprogressive familial form of muscular dystrophy with characteristic bone changes. Clin Orthop Relat Res 1959;14102- 109
Wallace  SELachman  RSMekikian  PBBui  KKWilcox  WR Marked phenotypic variability in progressive diaphyseal dysplasia (Camurati-Engelmann disease): report of a four-generation pedigree, identification of a mutation in TGFB1, and review. Am J Med Genet A 2004;129A (3) 235- 247
PubMed
Cohen  JStates  JD Progressive diaphyseal dysplasia: report of a case with autopsy findings. Lab Invest 1956;5 (6) 492- 508
PubMed
Bondestam  JMayranpaa  MKIkegawa  SMarttinen  EKroger  HMakitie  O Bone biopsy and densitometry findings in a child with Camurati-Engelmann disease. Clin Rheumatol 2007;26 (10) 1773- 1777
PubMed
Yoshioka  HMino  MKiyosawa  N  et al.  Muscular changes in Engelmann's disease. Arch Dis Child 1980;55 (9) 716- 719
PubMed
Kumar  BMurphy  WAWhyte  MP Progressive diaphyseal dysplasia (Engelmann disease): scintigraphic-radiographic-clinical correlations. Radiology 1981;140 (1) 87- 92
PubMed
Naveh  YKaftori  JKAlon  UBen-David  JBerant  M Progressive diaphyseal dysplasia: genetics and clinical and radiologic manifestations. Pediatrics 1984;74 (3) 399- 405
PubMed
Kaftori  JKKleinhaus  UNaveh  Y Progressive diaphyseal dysplasia (Camurati-Engelmann): radiographic follow-up and CT findings. Radiology 1987;164 (3) 777- 782
PubMed
Lennon  ESchechter  MHornabrook  R Engelmann's disease: report of a case with a review of the literature. J Bone Joint Surg Br 1961;43 (2) 273- 284
Makita  YNishimura  GIkegawa  SIshii  TIto  YOkuno  A Intrafamilial phenotypic variability in Engelmann disease (ED): are ED and Ribbing disease the same entity? Am J Med Genet 2000;91 (2) 153- 156
PubMed
Benecke  JE  Jr Facial nerve dysfunction in osteopetrosis. Laryngoscope 1993;103 (5) 494- 497
PubMed
Smith  RWalton  RJCorner  BDGordon  IR Clinical and biochemical studies in Engelmann's disease (progressive diaphyseal dysplasia). Q J Med 1977;46 (182) 273- 294
PubMed
Singleton  EBThomas  JRWorthington  WWHild  JR Progressive diaphyseal dysplasia (Engelmann's disease). Radiology 1956;67 (2) 233- 241
PubMed
Sparkes  RSGraham  CB Camurati-Engelmann disease: genetics and clinical manifestations with a review of the literature. J Med Genet 1972;9 (1) 73- 85
PubMed
Bedogni  C The vascular origin of Camurati-Engelmann disease (familial symmetrical sclerotic polyosteopathy) [in Italian]. Chir Organi Mov 1962;51156- 166
PubMed
Anczykowa  ABernasowska-Knapczykowa  KZamorska  L Camurati-Engelman syndrome in three siblings [in Polish]. Pol Przegl Radiol Med Nukl 1967;31 (2) 169- 178
PubMed
Trunk  GNewman  ADavis  TE Progressive and hereditary diaphyseal dysplasia: Engelmann's disease. Arch Intern Med 1969;123 (4) 417- 422
PubMed
Bourantas  KTsiara  SDrosos  AA Successful treatment with corticosteroid in a patient with progressive diaphyseal dysplasia. Clin Rheumatol 1995;14 (4) 485- 486
PubMed
Allen  DTSaunders  AMNorthway  WH  JrWilliams  GFSchafer  IA Corticosteroids in the treatment of Engelmann's disease: progressive diaphyseal dysplasia. Pediatrics 1970;46 (4) 523- 531
PubMed
Lindstrom  JA Diaphyseal dysplasia (Engelmann) treated with corticosteroids. Birth Defects Orig Artic Ser 1974;10 (12) 504- 507
PubMed
Minford  AMHardy  GJForsythe  WIFitton  JMRowe  VL Engelmann's disease and the effect of corticosteroids: a case report. J Bone Joint Surg Br 1981;63 (4) 597- 600
PubMed
Naveh  YLudatshcer  RAlon  USharf  B Muscle involvement in progressive diaphyseal dysplasia. Pediatrics 1985;76 (6) 944- 949
PubMed
Schapira  DMiliteanu  DIsrael  OMisselevich  IScharf  Y Progressive diaphyseal dysplasia masquerading as shoulder capsulitis in an adult. Clin Rheumatol 1995;14 (5) 582- 585
PubMed
Naveh  YAlon  UKaftori  JKBerant  M Progressive diaphyseal dysplasia: evaluation of corticosteroid therapy. Pediatrics 1985;75 (2) 321- 323
PubMed
Inaoka  TShuke  NSato  J  et al.  Scintigraphic evaluation of pamidronate and corticosteroid therapy in a patient with progressive diaphyseal dysplasia (Camurati-Engelmann disease). Clin Nucl Med 2001;26 (8) 680- 682
PubMed
Royer  PVermeil  GApostolides  PEngelmann  F Engelmann's disease: results of treatment with prednisone [in French]. Arch Fr Pediatr 1967;24 (6) 693- 702
PubMed
Baş  FDarendeliler  FPetorak  I  et al.  Deflazacort treatment in progressive diaphyseal dysplasia (Camurati-Engelmann disease). J Paediatr Child Health 1999;35 (4) 401- 405
PubMed
Heymans  OGebhart  MAlexiou  JSokolow  Y Camurati-Engelmann disease: effects of corticosteroids. Acta Clin Belg 1998;53 (3) 189- 192
PubMed
Iba  KTakada  JKamasaki  H  et al.  A significant improvement in lower limb pain after treatment with alendronate in two cases of Camurati-Engelmann disease. J Bone Miner Metab 2008;26 (1) 107- 109
PubMed
Simsek  SJanssens  KKwee  MLVan Hul  WVeenstra  JNetelenbos  JC Camurati-Engelmann disease (progressive diaphyseal dysplasia) in a Moroccan family. Osteoporos Int 2005;16 (9) 1167- 1170
PubMed
Castro  GRAppenzeller  SMarques-Neto  JFBertolo  MBSamara  AMCoimbra  I Camurati-Engelmann disease: failure of response to bisphosphonates: report of two cases. Clin Rheumatol 2005;24 (4) 398- 401
PubMed
Hellier  WPBrookes  GB Vestibular nerve dysfunction and decompression in Engelmann's disease. J Laryngol Otol 1996;110 (5) 462- 465
PubMed
Krohel  GBWirth  CR Engelmann's disease. Am J Ophthalmol 1977;84 (4) 520- 525
PubMed
Hanson  WParnes  LS Vestibular nerve compression in Camurati-Engelmann disease. Ann Otol Rhinol Laryngol 1995;104 (10, pt 1) 823- 825
PubMed
Moumoulidis  IDe  RRamsden  RMoffat  D Unusual otological manifestations in Camurati-Engelmann's disease. J Laryngol Otol 2006;120 (10) 892- 895
PubMed
Friedland  DRWackym  PARhee  JSFinn  MS Cochlear implantation for auditory rehabilitation in Camurati-Engelmann disease. Ann Otol Rhinol Laryngol 2000;109 (2) 160- 162
PubMed
Yen  JKBourke  RSPopp  AJWirth  CR Camurati-Engelmann disease (progressive hereditary craniodiaphyseal dysplasia): case report. J Neurosurg 1978;48 (1) 138- 142
PubMed
Dannenmaier  BWeber  B Observations on the Camurati-Engelmann syndrome: demonstration of changes of the petrous bone using high-resolution computed tomography [in German]. Rofo 1989;151 (2) 175- 178
PubMed
Morse  PHWalsh  FB McCormick  JR Ocular findings in hereditary diaphyseal cysplasia (Engelmann's disease). Am J Ophthalmol 1969;68 (1) 100- 104
PubMed
Hoeffel  JCMainard  LLeyder  B Camurati-Engelmann disease: a case report. Eur Radiol 1999;9 (9) 1932- 1933
PubMed
Wright  MMiller  NR McFadzean  RM  et al.  Papilloedema, a complication of progressive diaphyseal dysplasia: a series of three case reports. Br J Ophthalmol 1998;82 (9) 1042- 1048
PubMed
Stasolla  AMagliulo  GBellussi  AParrotto  DBibbolino  CMarini  M Imaging of the temporal bone in Camurati-Engelmann dysplasia with an 11-year follow-up. Otol Neurotol 2005;26 (4) 773- 777
PubMed
Antunes  MLTesta  JRFrazatto  RBarberi  JASilva  RF Rare osteodysplasia of the temporal bone. Braz J Otorhinolaryngol 2005;71 (2) 228- 232
PubMed
Paludetti  GGalli  ALombardi  RAlmadori  GPujolas  FXMaurizi  M Otolaryngological aspects of Camurati-Engelmann disease (progressive diaphyseal dysplasia): review of literature and report of one case [in Spanish]. Acta Otorrinolaringol Esp 1994;45 (3) 207- 213
PubMed
Mastragelopulos  NBahr  RPfister  U Camurati-Engelmann disease (progressive diaphyseal dysplasia): differential diagnostic problems [in German]. Unfallchirurgie 1989;15 (2) 104- 107
PubMed
Higashi  KMatsuki  C Hearing impairment in Engelmann disease. Am J Otol 1996;17 (1) 26- 29
PubMed
Fallon  MDWhyte  MPMurphy  WA Progressive diaphyseal dysplasia (Engelmann's disease): report of a sporadic case of the mild form. J Bone Joint Surg Am 1980;62 (3) 465- 472
PubMed
Wetzel  H Contribution on Camurati-Engelmann disease [in German]. Dtsch Med Wochenschr 1963;88188- 190
PubMed
Lenarz  TGülzow  J Neuro-otologic early symptoms of Camurati-Engelmann disease [in German]. Laryngol Rhinol Otol (Stuttg) 1983;62 (10) 463- 467
PubMed
Mineta  YKakigi  ROda  KOkue  AShibasaki  H Case of progressive diaphyseal dysplasia (Engelmann) presenting with trigeminal neuropathy and hearing disorder [in Japanese]. Rinsho Shinkeigaku 1983;23 (8) 700- 705
PubMed
Thelen  PO Familial occurrence of Camurati-Engelmann disease [in German]. Fortschr Geb Rontgenstr Nuklearmed 1961;94713- 717
PubMed
Paul  LW Hereditary multiple diaphyseal sclerosis (Ribbing). Radiology 1953;60 (3) 412- 416
PubMed
Hundley  JDWilson  FC Progessive diaphyseal dysplasia: review of the literature and report of seven cases in one family. J Bone Joint Surg Am 1973;55 (3) 461- 474
PubMed
Tucker  ASKlein  LAntony  GJ Craniodiaphyseal dysplasia: evolution over a five-year period. Skeletal Radiol 1976;147- 53doi:10.1007/BF00347727
Mottram  MEHill  HA Diaphyseal dysplasia: report of a case. Am J Roentgenol Radium Ther Nucl Med 1965;95162- 167
PubMed
Wilhelm  KRLenarz  TWeise  DBaldauf  GFritz  PBihl  H Value of various radiological study results in the follow-up of Camurati-Engelmann disease [in German]. Rofo 1987;147 (3) 278- 282
PubMed
Huygen  PLCremers  CWVerhagen  WIJoosten  FB Camurati-Engelmann disease presenting as “juvenile otosclerosis.” Int J Pediatr Otorhinolaryngol 1996;37 (2) 129- 141
PubMed
Tibesar  RJBrissett  AEShallop  JKDriscoll  CL Internal auditory canal decompression and cochlear implantation in Camurati-Engelmann disease. Otolaryngol Head Neck Surg 2004;131 (6) 1004- 1006
PubMed
Wolf  BHFord  HW An unusual radiographic manifestation of Engelmann's disease in a young Negro child. Radiology 1971;99 (2) 401- 402
PubMed
Mocco  JKomotar  RJZacharia  BEFeldstein  NABruce  JN Aggressive cranial vault decompression for cranial hyperostosis: technical case report of two cases. Neurosurgery 2005;57 (1) ((suppl)) E212
PubMeddoi:10.1227/01.NEU.0000163686.75095.B8
Albert  L  JrHirschfeld  A Acquired Chiari malformation secondary to hyperostosis of the skull: a case report and literature review. Surg Neurol 2009;72 (2) 157- 161
PubMed
van Buchem  FHadders  HNHansen  JFWoldring  MG Generalized cortical hyperostosis [in Dutch]. Ned Tijdschr Geneeskd 1963;10764- 74
PubMed
Soni  JPGupta  BDSoni  MMund  VAneja  R Engelmann's disease with optic atrophy. Indian J Pediatr 2002;69 (9) 823- 824
PubMed
Brodrick  JD Luxation of the globe in Engelmann's disease. Am J Ophthalmol 1977;83 (6) 870- 873
PubMed
Aggarwal  PWali  JPSharma  SK Progressive diaphyseal dysplasia: case report and literature review. Orthopedics 1990;13 (8) 901- 904
PubMed
Anderson  FG Engelmann's disease. Br J Radiol 1953;26 (311) 603- 605
PubMed
Ballardini  PGulmini  LMargutti  GLelli  G Mesenteric fibromatosis in a patient with Camurati-Engelmann disease: a case report and literature review. Tumori 2005;91 (6) 552- 554
PubMed
Battaglia  LVenturi  R Hereditary symmetrical hyperostotic polyosteopathy (Camurati-Engelmann disease): clinical and anatomopathological study [in Italian]. Chir Organi Mov 1960;49179- 196
PubMed
Bingold  AC Engelmann's disease: osteopathia hyperostotica (sclerotisans) multiplex infantilis: progressive diaphysial dysplasia. Br J Surg 1950;37 (147) 266- 274
PubMed
Brat  HGHamoir  XMatthijs  PLambin  PVan Campenhoudt  M Camurati-Engelmann disease: a late and sporadic case with metaphyseal involvement. Eur Radiol 1999;9 (1) 159- 162
PubMed
Byanyima  RKNabawesi  JB Camurati-Engelmann's disease: a case report. Afr Health Sci 2002;2 (3) 118- 120
PubMed
Bye  AMHodson  EKewley  GKozlowski  K Progressive diaphyseal dysplasia and a low muscle carnitine. Pediatr Radiol 1988;18 (4) 340
PubMed
Cerrato  PBaima  CBergui  M  et al.  Juvenile vertebrobasilar ischaemic stroke in a patient with Camurati-Engelmann disease. Cerebrovasc Dis 2005;20 (4) 283- 284
PubMed
Chérié-Lignière  GSantalena  GParafioriti  A Pamidronate in the treatment of progressive diaphyseal dysplasia (Camurati-Engelmann disease). Clin Exp Rheumatol 1999;17 (2) 264
PubMed
Chipps  JEPenner  RSTravis  LO Mandibular involvement in osteopathia hyperostotica sclerotisans multiplex infantilis (Engelmann's disease). Oral Surg Oral Med Oral Pathol 1954;7 (12) 1306- 1310
PubMed
Choudhury  PBatra  VBatra  BGandhi  D Engelmann's disease with cardiomyopathy. Indian Pediatr 2000;37 (12) 1373- 1376
PubMed
Clawson  DKLoop  JW Progressive diaphyseal dysplasia (Engelmann's disease). J Bone Joint Surg Am 1964;46143- 150
PubMed
Clybouw  CDesmyttere  SBonduelle  MPiepsz  A Camurati-Engelmann disease: contribution of bone scintigraphy to genetic counseling. Genet Couns 1994;5 (2) 195- 198
PubMed
Cohan  HJAbeya  ODobon  JFGutierrez  TSlaski  F Camurati-Engelmann osteopathy [in Spanish]. Prensa Med Argent 1962;491614- 1621
PubMed
Cozzolino  A More on the Camurati-Engelmann osteopathy [in Italian]. Arch Ortop 1959;721422- 1427
PubMed
Crisp  AJBrenton  DPShaw  DG Case report 202: Engelmann disease of bone (diaphyseal dysplasia) with bilateral shortened fibulae. Skeletal Radiol 1982;8 (3) 239- 240
PubMed
D’Addabbo  AMacarini  LRubini  GRubini  DSalzillo  FLauriero  F Correlation between bone imaging and the clinical picture in two unsuspected cases of progressive diaphyseal dysplasia (Engelmann's disease). Clin Nucl Med 1993;18 (4) 324- 328
PubMed
De La Barreda  POrtega  RTorres  JAFerrer  M A familial case of the Camurati-Engelmann disease [in Spanish]. Rev Clin Esp 1960;79196- 201
PubMed
De Vits  AKeymeulen  BBossuyt  ASomers  GVerbruggen  LA Progressive diaphyseal dysplasia (Camurati-Engelmann's disease): improvement of clinical signs and of bone scintigraphy during pregnancy. Clin Nucl Med 1994;19 (2) 104- 107
PubMed
Dell’Acqua  GBRuberti  APiffanelli  A Camurati-Engelmann disease: case contribution [in Italian]. Minerva Med 1963;541589- 1603
PubMed
Dharmadasa  KMendis  BLKarunanayake  Rde Silva  SP Engelmann–Camurati disease. Ceylon Med J 1981;26 (4) 178- 179
PubMed
Dumazer  RPorot  FBernard  P Maladie d’Engelmann premier cas Nord-Africain. J Radiol Electrol 1963;44314- 318
Fairbanks  TAn Atlas of General Affections of the Skeleton. Edinburgh, Scotland E & S Livingstone1951;
Farreras Valenti  PVilaseca  JMDe Caralt  M Hereditary multiple diaphysial osteosclerosis of the Camurati-Engelmann type with leontiasis ossium syndrome [in Spanish]. Rev Esp Reumatol 1954;5 (6) 354- 362
PubMed
Fritsch  H Ein Fall von generalisierter osteosklerose. Wien Arch f inn Med 1932;23247- 256
Furia  JPSchwartz  HS Hereditary multiple diaphyseal sclerosis: a tumor simulator. Orthopedics 1990;13 (11) 1267- 1274
PubMed
Gelli  GPArioni  G Camurati-Engelmann multiple sclerosing hyperostotic osteopathy [in Italian]. Minerva Pediatr 1974;26 (15) 772- 778
PubMed
Gillespie  JBMussey  R Progressive diaphyseal dysplasia (Engelmann's disease). J Pediatr 1951;38 (1) 55- 59
PubMed
Goerke  H On another family with Camurati-Engelmann's disease (CEE) [in German]. Fortschr Geb Rontgenstr Nuklearmed 1960;92106- 109
PubMed
González Espinosa  CPerez Albelo  TCerrudo Hernández  RCHernández Gonzalez  JRFernández  JToledo Trujillo  F Progressive diaphyseal dysplasia with unusual bone involvement (Camurati-Engelmann disease) [in Spanish]. An Esp Pediatr 1991;34 (1) 71- 73
PubMed
Grey  ACWallace  RCrone  M Engelmann's disease: a 45-year follow-up. J Bone Joint Surg Br 1996;78 (3) 488- 491
PubMed
Griffiths  DL Engelmann's disease. J Bone Joint Surg Br 1956;38 (1) 312- 326
PubMed
Gulati  PDBhardwaj  OPVyas  PB Case of Englemann's disease. (With special plate) Br Med J 1967;3 (5559) 217
PubMed
Gulledge  WHWhite  JW Englemann's disease (progressive diaphyseal hyperostosis): report of a case. J Bone Joint Surg Am 1951;33 (3) 793- 797
PubMed
Gupta  SCheikh  IE Camurati-Engelmann disease in conjunction with hypogonadism. Endocr Pract 2005;11 (6) 399- 407
PubMed
Gvozdanovic  V New case of Engelmann's disease (congenital osteodystrophy) [in German]. Fortschr Geb Rontgenstr 1950;73 (1) 86- 89
PubMed
Hernández  MVPeris  PGuañabens  N  et al.  Biochemical markers of bone turnover in Camurati-Engelmann disease: a report on four cases in one family. Calcif Tissue Int 1997;61 (1) 48- 51
PubMed
Jackson  WPHanelin  JAlbright  F Metaphyseal dysplasia, epiphyseal dysplasia, diaphyseal dysplasia, and related conditions, III: progressive diaphyseal dysplasia. AMA Arch Intern Med 1954;94 (6) 902- 910
PubMed
Duclos  GJammes  AProuzet  JSerny  R Engelmann's disease: study of two familial cases [in French]. Presse Med 1956;24 (64) 1759- 1761
PubMed
Jammes  ASerny  RProuzet  JDuclos  G Engelmann's disease: hyperostotic and multiple sclerosing infantile osteopathy [in French]. Rev Rhum Mal Osteoartic 1953;20 (5) 406- 414
PubMed
Kormas  NDiamond  TShnier  R Camurati-Engelmann disease: two case reports describing metadiaphyseal dysplasia associated with cerebellar ataxia. J Bone Miner Res 1998;13 (7) 1203- 1207
PubMed
Kuhlencordt  FKruse  HPHellner  KAMontz  R Diaphyseal dysplasia (Camurati-Engelmann syndrome) with progressive loss of vision: 30-year observations and the effect of prednisolone treatment [author's translation] [in German]. Dtsch Med Wochenschr 1981;106 (19) 617- 621
PubMed
Lauterberg  W Uber zwei falle von familiarer generalisierter osteosklerose. Deutsche Ztschr f Chir 1931;230308- 315
Lavine  LSKoven  MT Engelmann's disease (progressive diaphyseal dysplasia). J Pediatr 1952;40 (2) 235- 239
PubMed
Lazzarone  CCartesegna  MCrova  MCalorio  D Progressive diaphyseal dysplasia: Camurati-Engelmann's disease. Ital J Orthop Traumatol 1983;9 (1) 109- 114
PubMed
LeBien  WEHeilman  C Progressive diaphyseal dysplasia: with report of a case. J Lancet 1951;71 (5) 189- 192
PubMed
Lelek  I Camurati-Engelmann disease [in German]. Fortschr Geb Rontgenstr Nuklearmed 1961;94702- 712
PubMed
Da Lima  LCRocha  M Engelmann's disease: progressive diaphyseal dysplasia [in Portuguese]. Rev Bras Cir 1952;24 (2) 281- 296
PubMed
Lücke  TIllsinger  SDas  AMSchirg  EHartmann  H Pitfalls in paediatric gait disturbances: painless bone diseases. Eur J Pediatr 2006;165 (12) 909- 912
PubMed
Lundy  MMBillingsley  JLRedwine  MDTurnbull  GLBrown  TJ Scintigraphic findings in progressive diaphyseal dysplasia. J Nucl Med 1982;23 (4) 324- 325
PubMed
Magnant  JSCampourcy  ABouville  J Engelmann's syndrome [in French]. J Chir (Paris) 1963;86293- 302
PubMed
Massé  GParenti  G Considerations on Camurati-Engelmann hereditary symmetrical osteopathia addensans [in Italian]. Arch Sci Med (Torino) 1966;122 (2) 92- 104
PubMed
Michaelis  LS Engelmann's disease. Proc R Soc Med 1949;42 (4) 271- 273
PubMed
Mikity  VGJacobson  G Progressive diaphyseal dysplasia (Engelmann's disease): report of a case with twenty-two–year follow-up. J Bone Joint Surg Am 1958;40 (1) 206- 210
PubMed
Mishra  GKMishra  MVernekar  JTehrai  MPatel  BR Progressive diaphyseal dysplasia: Engelmann's disease. Indian Pediatr 1987;24 (11) 1052- 1054
PubMed
Moudgil  AAgarwal  RKPati  HBagga  ASaraya  AK Camurati-Engelmann disease with recurrent bone marrow hypoplasia. Indian J Pediatr 1985;52 (415) 201- 204
PubMed
Narang  DBharati  BBhattacharya  AMittal  BR Radionuclide bone scintigraphy in Engelmann-Camurati disease. Arch Dis Child 2004;89 (8) 737
PubMed
Nelson  MScott  C Engelmann's disease (a form of craniodiaphyseal dysplasia). Birth Defects 1969;4301- 304
Neuhauser  EBSchwachman  HWittenborg  MCohen  J Progressive diaphyseal dysplasia. Radiology 1948;51 (1) 11- 22
PubMed
Newman  ATrunk  G Late roentgen sequelae of Engelmann's disease. Int Surg 1970;53 (1) 28- 32
PubMed
Nowicki  RWNorris  A Caesarean section in a patient with Engelmann's disease. Anaesthesia 1999;54 (11) 1118- 1119
PubMed
Ortolani  MCastagnari  G L’ostopatia di Camurati-Engelmann. Arch Putti Chir Organi Mov 1953;3146- 165
Panja  SChatterjee  SBasak  MChatterjee  R Progressive diaphyseal dysplasia (Camurati-Engelmann's disease). Indian Pediatr 1984;21 (8) 653- 655
PubMed
Patz  IM Engelmann's disease: case report and brief review. S Afr Med J 1960;34116- 119
PubMed
Perassi  F Camurati-Engelmann disease: sclerotic diaphysial symmetric hereditary hyperostosis [in Italian]. Radiol Med 1954;40 (2) 147- 159
PubMed
Raffaelli  PRonzini  MF Camurati-Engelmann's disease: a case report. Ital J Orthop Traumatol 1988;14 (2) 267- 271
PubMed
Ramanan  AVHall  MJBaildam  EMMughal  Z Camurati-Engelmann disease: a case report and literature review. Rheumatology (Oxford) 2005;44 (8) 1069- 1072
PubMed
Ribbing  S Hereditary, multiple, diaphyseal sclerosis. Acta Radiol 1949;31 (5-6) 522- 536
PubMed
Roth  J Hyperostosis generalisata, Camurati-Engelmann type. Harefuah 1957;52 (9) 223- 229
PubMed
Ruelle  MDubois  JL Apropos of 2 familial cases of multiple diaphyseal sclerosis (Camurati-Engelmann syndrome) [in French]. Rev Rhum Mal Osteoartic 1964;31345- 348
PubMed
Schollaert  EPouders  EMatton  PClaessens  HVan de Velde  E Diaphyseal dysplasia: late radiological discovery of 3 familial cases. J Belge Radiol 1983;66 (2) 93- 99
PubMed
Sear  HR Engelmann's disease: osteopathia hyperostotica sclerotisans multiplex infantilis: report of a case. Br J Radiol 1948;21 (245) 236- 241
PubMed
Shier  CKKrasicky  GAEllis  BIKottamasu  SR Ribbing's disease: radiographic-scintigraphic correlation and comparative analysis with Engelmann's disease. J Nucl Med 1987;28 (2) 244- 248
PubMed
Shuke  NTakashio  TYamamoto  W  et al.  Bone scintigraphy in a patient with progressive diaphyseal dysplasia. Clin Nucl Med 1997;22 (11) 791- 792
PubMed
Stegman  KFPeterson  JC Progressive hereditary diaphyseal dysplasia. Pediatrics 1957;20 (6) 966- 974
PubMed
Stenzler  SGrogan  DPFrenchman  SM McClelland  SOgden  JA Progressive diaphyseal dysplasia presenting as neuromuscular disease. J Pediatr Orthop 1989;9 (4) 463- 467
PubMed
Stewart  HBCole  ER Progressive diaphysial dysplasia (Englemann's disease). J Pediatr 1956;48 (4) 482- 485
PubMed
Stirpe  M Exophthalmos and convergence insufficiency in Camurati-Engelmann disease [in Italian]. Boll Ocul 1965;44 (9) 625- 646
PubMed
Stronge  R McDowell  H A case of Engelmann's disease progressive diaphysial dysplasia. J Bone Joint Surg Br 1950;32 (1) 38- 39
Sty  JRBabbitt  DPStarshak  RJ Bone scintigraphy demonstrating Engelmann's disease. Clin Nucl Med 1978;3 (2) 69- 70
PubMed
Verbruggen  LABossuyt  ASchreuer  RSomers  G Clinical and scintigraphic evaluation of corticosteroid treatment in a case of progressive diaphyseal dysplasia. J Rheumatol 1985;12 (4) 809- 813
PubMed
Viviani  G A case of Camurati-Engelmann disease [in Italian]. Ann Radiol Diagn (Bologna) 1960;33340- 352
PubMed
Weingraber  H A new observation in a case of osteopathia hyperostotica Engelmann-Camurati [in German]. Fortschr Geb Rontgenstr 1954;81 (6) 800- 804
PubMed
Whyte  MP Heritable metabolic and dysplastic bone diseases. Endocrinol Metab Clin North Am 1990;19 (1) 133- 173
PubMed
Wiedemann  H Systematisierte sklerotische Hyperostose des Kindesalters mit Myopathie. Ztschr f Kinderheilk 1948;65346- 347
Willems  DVerhelst  MMulier  JCMartens  M Engelmann's disease: report of four cases with review of literature. J Belge Radiol 1973;56 (5) 395- 398
PubMed
Wu  SLiang  SYan  Y  et al.  A novel mutation of TGFβ1 in a Chinese family with Camurati-Engelmann disease. Bone 2007;40 (6) 1630- 1634
PubMed
Yvars  MF Engelmann's disease: a case report. Clin Orthop Relat Res 1969;62206- 208
PubMed
Beighton  PDurr  LHamersma  H The clinical features of sclerosteosis: a review of the manifestations in twenty-five affected individuals. Ann Intern Med 1976;84 (4) 393- 397
PubMed
Saraiva  JM Anticipation in progressive diaphyseal dysplasia. J Med Genet 2000;37 (5) 394- 395
PubMed
Kirkpatrick  DBRimoin  DLKaitila  IGoodman  SJ The craniotubular bone modeling disorders: a neurosurgical introduction to rare skeletal dysplasias with cranial nerve compression. Surg Neurol 1977;7 (4) 221- 232
PubMed
Shelton  CLuxford  WMTonokawa  LLLo  WWHouse  WF The narrow internal auditory canal in children: a contraindication to cochlear implants. Otolaryngol Head Neck Surg 1989;100 (3) 227- 231
PubMed
Hamersma  HMay  MOsteopetrosis and Facial Palsy: The Facial Nerve. 2nd ed. New York, NY Thieme Inc2000;409- 421
Hamersma  H Total decompression of the facial nerve in osteopetrosis (marble bone disease-morbus Albers-Schönberg). ORL J Otorhinolaryngol Relat Spec 1974;36 (1) 21- 32
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Clinical findings in patient 5 (Table 1) with Camurati-Engelmann disease. Bilateral exophthalmia (A), square jaw line and frontal bossing (B), bony overgrowth of the mandible (C), and thickened craniotomy bone plate during a middle fossa approach (D) are demonstrated.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Preoperative and postoperative computed tomographic (CT) images in patient 5 (see Table 1) with Camurati-Engelmann disease. Preoperative left-sided coronal (A) and axial (B) high-resolution CT images of the temporal bone demonstrating bony overgrowth of the internal auditory canal (arrows). Postoperative coronal (C) and axial (D) CT images of the left temporal bone demonstrating interval decompression of the facial and vestibulocochlear nerve complex (arrows) through a middle fossa craniotomy.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Demographic Data, Findings, and Surgical Treatments in Patients Diagnosed as Having CED-Associated Skull Base Involvement
Table Graphic Jump LocationTable 2. Prevalence of Skull Base Manifestations Among 306 Published Cases

References

Gorlin  RCohen  MHennekam  RSyndromes of the Head and Neck. 4th ed. New York, NY Oxford University Press2001;
Cockayne  E Case for diagnosis. Proc R Soc Med 1920;13132- 136
PubMed
Camurati  M Di un raro caso di osteite simmetrica ereditaria degli arti inferiori. Chir Organi Mov 1922;6662- 665
Engelmann  G Ein Fall von Osteopathia hyperostotica multiplex infantilis. Fortschr Geb Rontgenstr Nuklearmed 1929;391101- 1106
Janssens  Kten Dijke  PRalston  SHBergmann  CVan Hul  W Transforming growth factor-β1 mutations in Camurati-Engelmann disease lead to increased signaling by altering either activation or secretion of the mutant protein. J Biol Chem 2003;278 (9) 7718- 7724
PubMed
Kinoshita  ASaito  TTomita  H  et al.  Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease. Nat Genet 2000;26 (1) 19- 20
PubMed
Campos-Xavier  BSaraiva  JMSavarirayan  R  et al.  Phenotypic variability at the TGF-β1 locus in Camurati-Engelmann disease. Hum Genet 2001;109 (6) 653- 658
PubMed
Ghadami  MMakita  YYoshida  K  et al.  Genetic mapping of the Camurati-Engelmann disease locus to chromosome 19q13.1-q13.3. Am J Hum Genet 2000;66 (1) 143- 147
PubMed
Janssens  KGershoni-Baruch  RVan Hul  E  et al.  Localisation of the gene causing diaphyseal dysplasia Camurati-Engelmann to chromosome 19q13. J Med Genet 2000;37 (4) 245- 249
PubMed
Saito  TKinoshita  AYoshiura  K-i  et al.  Domain-specific mutations of a transforming growth factor (TGF)-β1 latency-associated peptide cause Camurati-Engelmann disease because of the formation of a constitutively active form of TGF-β1. J Biol Chem 2001;276 (15) 11469- 11472
PubMed
Janssens  Kten Dijke  PJanssens  SVan Hul  W Transforming growth factor-β1 to the bone. Endocr Rev 2005;26 (6) 743- 774
PubMed
Janssens  KVanhoenacker  FBonduelle  M  et al.  Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment. J Med Genet 2006;43 (1) 1- 11
PubMed
Ramon  YBuchner  A Camurati-Engelmann's disease affecting the jaws. Oral Surg Oral Med Oral Pathol 1966;22 (5) 592- 599
PubMed
Crisp  AJBrenton  DP Engelmann's disease of bone: a systemic disorder? Ann Rheum Dis 1982;41 (2) 183- 188
PubMed
Demas  PNSotereanos  GC Facial-skeletal manifestations of Engelmann's disease. Oral Surg Oral Med Oral Pathol 1989;68 (6) 686- 690
PubMed
Miyamoto  RTHouse  WFBrackmann  DE Neurotologic manifestations of the osteopetroses. Arch Otolaryngol 1980;106 (4) 210- 214
PubMed
Applegate  LJApplegate  GRKemp  SS MR of multiple cranial neuropathies in a patient with camurati-engelmann disease: case report. AJNR Am J Neuroradiol 1991;12 (3) 557- 559
PubMed
Simpson  RK  JrFischer  DKGall  GKRose  JE Fatal cerebellar herniation secondary to Camurati-Englemann's disease. J Neurol Neurosurg Psychiatry 1988;51 (10) 1349- 1352
PubMed
van Dalsem  VFGenant  HKNewton  TH Progressive diaphyseal dysplasia: report of a case with thirty-four years of progressive disease. J Bone Joint Surg Am 1979;61 (4) 596- 598
PubMed
Saraiva  JM Progressive diaphyseal dysplasia: a three-generation family with markedly variable expressivity. Am J Med Genet 1997;71 (3) 348- 352
PubMed
Low  LCStephenson  JBStuart-Smith  DA Progressive diaphyseal dysplasia mimicking childhood myopathy: clinical and biochemical response to prednisolone. Aust Paediatr J 1985;21 (3) 193- 196
PubMed
Girdany  B Engelmann's disease (progressive diaphyseal dysplasia): a nonprogressive familial form of muscular dystrophy with characteristic bone changes. Clin Orthop Relat Res 1959;14102- 109
Wallace  SELachman  RSMekikian  PBBui  KKWilcox  WR Marked phenotypic variability in progressive diaphyseal dysplasia (Camurati-Engelmann disease): report of a four-generation pedigree, identification of a mutation in TGFB1, and review. Am J Med Genet A 2004;129A (3) 235- 247
PubMed
Cohen  JStates  JD Progressive diaphyseal dysplasia: report of a case with autopsy findings. Lab Invest 1956;5 (6) 492- 508
PubMed
Bondestam  JMayranpaa  MKIkegawa  SMarttinen  EKroger  HMakitie  O Bone biopsy and densitometry findings in a child with Camurati-Engelmann disease. Clin Rheumatol 2007;26 (10) 1773- 1777
PubMed
Yoshioka  HMino  MKiyosawa  N  et al.  Muscular changes in Engelmann's disease. Arch Dis Child 1980;55 (9) 716- 719
PubMed
Kumar  BMurphy  WAWhyte  MP Progressive diaphyseal dysplasia (Engelmann disease): scintigraphic-radiographic-clinical correlations. Radiology 1981;140 (1) 87- 92
PubMed
Naveh  YKaftori  JKAlon  UBen-David  JBerant  M Progressive diaphyseal dysplasia: genetics and clinical and radiologic manifestations. Pediatrics 1984;74 (3) 399- 405
PubMed
Kaftori  JKKleinhaus  UNaveh  Y Progressive diaphyseal dysplasia (Camurati-Engelmann): radiographic follow-up and CT findings. Radiology 1987;164 (3) 777- 782
PubMed
Lennon  ESchechter  MHornabrook  R Engelmann's disease: report of a case with a review of the literature. J Bone Joint Surg Br 1961;43 (2) 273- 284
Makita  YNishimura  GIkegawa  SIshii  TIto  YOkuno  A Intrafamilial phenotypic variability in Engelmann disease (ED): are ED and Ribbing disease the same entity? Am J Med Genet 2000;91 (2) 153- 156
PubMed
Benecke  JE  Jr Facial nerve dysfunction in osteopetrosis. Laryngoscope 1993;103 (5) 494- 497
PubMed
Smith  RWalton  RJCorner  BDGordon  IR Clinical and biochemical studies in Engelmann's disease (progressive diaphyseal dysplasia). Q J Med 1977;46 (182) 273- 294
PubMed
Singleton  EBThomas  JRWorthington  WWHild  JR Progressive diaphyseal dysplasia (Engelmann's disease). Radiology 1956;67 (2) 233- 241
PubMed
Sparkes  RSGraham  CB Camurati-Engelmann disease: genetics and clinical manifestations with a review of the literature. J Med Genet 1972;9 (1) 73- 85
PubMed
Bedogni  C The vascular origin of Camurati-Engelmann disease (familial symmetrical sclerotic polyosteopathy) [in Italian]. Chir Organi Mov 1962;51156- 166
PubMed
Anczykowa  ABernasowska-Knapczykowa  KZamorska  L Camurati-Engelman syndrome in three siblings [in Polish]. Pol Przegl Radiol Med Nukl 1967;31 (2) 169- 178
PubMed
Trunk  GNewman  ADavis  TE Progressive and hereditary diaphyseal dysplasia: Engelmann's disease. Arch Intern Med 1969;123 (4) 417- 422
PubMed
Bourantas  KTsiara  SDrosos  AA Successful treatment with corticosteroid in a patient with progressive diaphyseal dysplasia. Clin Rheumatol 1995;14 (4) 485- 486
PubMed
Allen  DTSaunders  AMNorthway  WH  JrWilliams  GFSchafer  IA Corticosteroids in the treatment of Engelmann's disease: progressive diaphyseal dysplasia. Pediatrics 1970;46 (4) 523- 531
PubMed
Lindstrom  JA Diaphyseal dysplasia (Engelmann) treated with corticosteroids. Birth Defects Orig Artic Ser 1974;10 (12) 504- 507
PubMed
Minford  AMHardy  GJForsythe  WIFitton  JMRowe  VL Engelmann's disease and the effect of corticosteroids: a case report. J Bone Joint Surg Br 1981;63 (4) 597- 600
PubMed
Naveh  YLudatshcer  RAlon  USharf  B Muscle involvement in progressive diaphyseal dysplasia. Pediatrics 1985;76 (6) 944- 949
PubMed
Schapira  DMiliteanu  DIsrael  OMisselevich  IScharf  Y Progressive diaphyseal dysplasia masquerading as shoulder capsulitis in an adult. Clin Rheumatol 1995;14 (5) 582- 585
PubMed
Naveh  YAlon  UKaftori  JKBerant  M Progressive diaphyseal dysplasia: evaluation of corticosteroid therapy. Pediatrics 1985;75 (2) 321- 323
PubMed
Inaoka  TShuke  NSato  J  et al.  Scintigraphic evaluation of pamidronate and corticosteroid therapy in a patient with progressive diaphyseal dysplasia (Camurati-Engelmann disease). Clin Nucl Med 2001;26 (8) 680- 682
PubMed
Royer  PVermeil  GApostolides  PEngelmann  F Engelmann's disease: results of treatment with prednisone [in French]. Arch Fr Pediatr 1967;24 (6) 693- 702
PubMed
Baş  FDarendeliler  FPetorak  I  et al.  Deflazacort treatment in progressive diaphyseal dysplasia (Camurati-Engelmann disease). J Paediatr Child Health 1999;35 (4) 401- 405
PubMed
Heymans  OGebhart  MAlexiou  JSokolow  Y Camurati-Engelmann disease: effects of corticosteroids. Acta Clin Belg 1998;53 (3) 189- 192
PubMed
Iba  KTakada  JKamasaki  H  et al.  A significant improvement in lower limb pain after treatment with alendronate in two cases of Camurati-Engelmann disease. J Bone Miner Metab 2008;26 (1) 107- 109
PubMed
Simsek  SJanssens  KKwee  MLVan Hul  WVeenstra  JNetelenbos  JC Camurati-Engelmann disease (progressive diaphyseal dysplasia) in a Moroccan family. Osteoporos Int 2005;16 (9) 1167- 1170
PubMed
Castro  GRAppenzeller  SMarques-Neto  JFBertolo  MBSamara  AMCoimbra  I Camurati-Engelmann disease: failure of response to bisphosphonates: report of two cases. Clin Rheumatol 2005;24 (4) 398- 401
PubMed
Hellier  WPBrookes  GB Vestibular nerve dysfunction and decompression in Engelmann's disease. J Laryngol Otol 1996;110 (5) 462- 465
PubMed
Krohel  GBWirth  CR Engelmann's disease. Am J Ophthalmol 1977;84 (4) 520- 525
PubMed
Hanson  WParnes  LS Vestibular nerve compression in Camurati-Engelmann disease. Ann Otol Rhinol Laryngol 1995;104 (10, pt 1) 823- 825
PubMed
Moumoulidis  IDe  RRamsden  RMoffat  D Unusual otological manifestations in Camurati-Engelmann's disease. J Laryngol Otol 2006;120 (10) 892- 895
PubMed
Friedland  DRWackym  PARhee  JSFinn  MS Cochlear implantation for auditory rehabilitation in Camurati-Engelmann disease. Ann Otol Rhinol Laryngol 2000;109 (2) 160- 162
PubMed
Yen  JKBourke  RSPopp  AJWirth  CR Camurati-Engelmann disease (progressive hereditary craniodiaphyseal dysplasia): case report. J Neurosurg 1978;48 (1) 138- 142
PubMed
Dannenmaier  BWeber  B Observations on the Camurati-Engelmann syndrome: demonstration of changes of the petrous bone using high-resolution computed tomography [in German]. Rofo 1989;151 (2) 175- 178
PubMed
Morse  PHWalsh  FB McCormick  JR Ocular findings in hereditary diaphyseal cysplasia (Engelmann's disease). Am J Ophthalmol 1969;68 (1) 100- 104
PubMed
Hoeffel  JCMainard  LLeyder  B Camurati-Engelmann disease: a case report. Eur Radiol 1999;9 (9) 1932- 1933
PubMed
Wright  MMiller  NR McFadzean  RM  et al.  Papilloedema, a complication of progressive diaphyseal dysplasia: a series of three case reports. Br J Ophthalmol 1998;82 (9) 1042- 1048
PubMed
Stasolla  AMagliulo  GBellussi  AParrotto  DBibbolino  CMarini  M Imaging of the temporal bone in Camurati-Engelmann dysplasia with an 11-year follow-up. Otol Neurotol 2005;26 (4) 773- 777
PubMed
Antunes  MLTesta  JRFrazatto  RBarberi  JASilva  RF Rare osteodysplasia of the temporal bone. Braz J Otorhinolaryngol 2005;71 (2) 228- 232
PubMed
Paludetti  GGalli  ALombardi  RAlmadori  GPujolas  FXMaurizi  M Otolaryngological aspects of Camurati-Engelmann disease (progressive diaphyseal dysplasia): review of literature and report of one case [in Spanish]. Acta Otorrinolaringol Esp 1994;45 (3) 207- 213
PubMed
Mastragelopulos  NBahr  RPfister  U Camurati-Engelmann disease (progressive diaphyseal dysplasia): differential diagnostic problems [in German]. Unfallchirurgie 1989;15 (2) 104- 107
PubMed
Higashi  KMatsuki  C Hearing impairment in Engelmann disease. Am J Otol 1996;17 (1) 26- 29
PubMed
Fallon  MDWhyte  MPMurphy  WA Progressive diaphyseal dysplasia (Engelmann's disease): report of a sporadic case of the mild form. J Bone Joint Surg Am 1980;62 (3) 465- 472
PubMed
Wetzel  H Contribution on Camurati-Engelmann disease [in German]. Dtsch Med Wochenschr 1963;88188- 190
PubMed
Lenarz  TGülzow  J Neuro-otologic early symptoms of Camurati-Engelmann disease [in German]. Laryngol Rhinol Otol (Stuttg) 1983;62 (10) 463- 467
PubMed
Mineta  YKakigi  ROda  KOkue  AShibasaki  H Case of progressive diaphyseal dysplasia (Engelmann) presenting with trigeminal neuropathy and hearing disorder [in Japanese]. Rinsho Shinkeigaku 1983;23 (8) 700- 705
PubMed
Thelen  PO Familial occurrence of Camurati-Engelmann disease [in German]. Fortschr Geb Rontgenstr Nuklearmed 1961;94713- 717
PubMed
Paul  LW Hereditary multiple diaphyseal sclerosis (Ribbing). Radiology 1953;60 (3) 412- 416
PubMed
Hundley  JDWilson  FC Progessive diaphyseal dysplasia: review of the literature and report of seven cases in one family. J Bone Joint Surg Am 1973;55 (3) 461- 474
PubMed
Tucker  ASKlein  LAntony  GJ Craniodiaphyseal dysplasia: evolution over a five-year period. Skeletal Radiol 1976;147- 53doi:10.1007/BF00347727
Mottram  MEHill  HA Diaphyseal dysplasia: report of a case. Am J Roentgenol Radium Ther Nucl Med 1965;95162- 167
PubMed
Wilhelm  KRLenarz  TWeise  DBaldauf  GFritz  PBihl  H Value of various radiological study results in the follow-up of Camurati-Engelmann disease [in German]. Rofo 1987;147 (3) 278- 282
PubMed
Huygen  PLCremers  CWVerhagen  WIJoosten  FB Camurati-Engelmann disease presenting as “juvenile otosclerosis.” Int J Pediatr Otorhinolaryngol 1996;37 (2) 129- 141
PubMed
Tibesar  RJBrissett  AEShallop  JKDriscoll  CL Internal auditory canal decompression and cochlear implantation in Camurati-Engelmann disease. Otolaryngol Head Neck Surg 2004;131 (6) 1004- 1006
PubMed
Wolf  BHFord  HW An unusual radiographic manifestation of Engelmann's disease in a young Negro child. Radiology 1971;99 (2) 401- 402
PubMed
Mocco  JKomotar  RJZacharia  BEFeldstein  NABruce  JN Aggressive cranial vault decompression for cranial hyperostosis: technical case report of two cases. Neurosurgery 2005;57 (1) ((suppl)) E212
PubMeddoi:10.1227/01.NEU.0000163686.75095.B8
Albert  L  JrHirschfeld  A Acquired Chiari malformation secondary to hyperostosis of the skull: a case report and literature review. Surg Neurol 2009;72 (2) 157- 161
PubMed
van Buchem  FHadders  HNHansen  JFWoldring  MG Generalized cortical hyperostosis [in Dutch]. Ned Tijdschr Geneeskd 1963;10764- 74
PubMed
Soni  JPGupta  BDSoni  MMund  VAneja  R Engelmann's disease with optic atrophy. Indian J Pediatr 2002;69 (9) 823- 824
PubMed
Brodrick  JD Luxation of the globe in Engelmann's disease. Am J Ophthalmol 1977;83 (6) 870- 873
PubMed
Aggarwal  PWali  JPSharma  SK Progressive diaphyseal dysplasia: case report and literature review. Orthopedics 1990;13 (8) 901- 904
PubMed
Anderson  FG Engelmann's disease. Br J Radiol 1953;26 (311) 603- 605
PubMed
Ballardini  PGulmini  LMargutti  GLelli  G Mesenteric fibromatosis in a patient with Camurati-Engelmann disease: a case report and literature review. Tumori 2005;91 (6) 552- 554
PubMed
Battaglia  LVenturi  R Hereditary symmetrical hyperostotic polyosteopathy (Camurati-Engelmann disease): clinical and anatomopathological study [in Italian]. Chir Organi Mov 1960;49179- 196
PubMed
Bingold  AC Engelmann's disease: osteopathia hyperostotica (sclerotisans) multiplex infantilis: progressive diaphysial dysplasia. Br J Surg 1950;37 (147) 266- 274
PubMed
Brat  HGHamoir  XMatthijs  PLambin  PVan Campenhoudt  M Camurati-Engelmann disease: a late and sporadic case with metaphyseal involvement. Eur Radiol 1999;9 (1) 159- 162
PubMed
Byanyima  RKNabawesi  JB Camurati-Engelmann's disease: a case report. Afr Health Sci 2002;2 (3) 118- 120
PubMed
Bye  AMHodson  EKewley  GKozlowski  K Progressive diaphyseal dysplasia and a low muscle carnitine. Pediatr Radiol 1988;18 (4) 340
PubMed
Cerrato  PBaima  CBergui  M  et al.  Juvenile vertebrobasilar ischaemic stroke in a patient with Camurati-Engelmann disease. Cerebrovasc Dis 2005;20 (4) 283- 284
PubMed
Chérié-Lignière  GSantalena  GParafioriti  A Pamidronate in the treatment of progressive diaphyseal dysplasia (Camurati-Engelmann disease). Clin Exp Rheumatol 1999;17 (2) 264
PubMed
Chipps  JEPenner  RSTravis  LO Mandibular involvement in osteopathia hyperostotica sclerotisans multiplex infantilis (Engelmann's disease). Oral Surg Oral Med Oral Pathol 1954;7 (12) 1306- 1310
PubMed
Choudhury  PBatra  VBatra  BGandhi  D Engelmann's disease with cardiomyopathy. Indian Pediatr 2000;37 (12) 1373- 1376
PubMed
Clawson  DKLoop  JW Progressive diaphyseal dysplasia (Engelmann's disease). J Bone Joint Surg Am 1964;46143- 150
PubMed
Clybouw  CDesmyttere  SBonduelle  MPiepsz  A Camurati-Engelmann disease: contribution of bone scintigraphy to genetic counseling. Genet Couns 1994;5 (2) 195- 198
PubMed
Cohan  HJAbeya  ODobon  JFGutierrez  TSlaski  F Camurati-Engelmann osteopathy [in Spanish]. Prensa Med Argent 1962;491614- 1621
PubMed
Cozzolino  A More on the Camurati-Engelmann osteopathy [in Italian]. Arch Ortop 1959;721422- 1427
PubMed
Crisp  AJBrenton  DPShaw  DG Case report 202: Engelmann disease of bone (diaphyseal dysplasia) with bilateral shortened fibulae. Skeletal Radiol 1982;8 (3) 239- 240
PubMed
D’Addabbo  AMacarini  LRubini  GRubini  DSalzillo  FLauriero  F Correlation between bone imaging and the clinical picture in two unsuspected cases of progressive diaphyseal dysplasia (Engelmann's disease). Clin Nucl Med 1993;18 (4) 324- 328
PubMed
De La Barreda  POrtega  RTorres  JAFerrer  M A familial case of the Camurati-Engelmann disease [in Spanish]. Rev Clin Esp 1960;79196- 201
PubMed
De Vits  AKeymeulen  BBossuyt  ASomers  GVerbruggen  LA Progressive diaphyseal dysplasia (Camurati-Engelmann's disease): improvement of clinical signs and of bone scintigraphy during pregnancy. Clin Nucl Med 1994;19 (2) 104- 107
PubMed
Dell’Acqua  GBRuberti  APiffanelli  A Camurati-Engelmann disease: case contribution [in Italian]. Minerva Med 1963;541589- 1603
PubMed
Dharmadasa  KMendis  BLKarunanayake  Rde Silva  SP Engelmann–Camurati disease. Ceylon Med J 1981;26 (4) 178- 179
PubMed
Dumazer  RPorot  FBernard  P Maladie d’Engelmann premier cas Nord-Africain. J Radiol Electrol 1963;44314- 318
Fairbanks  TAn Atlas of General Affections of the Skeleton. Edinburgh, Scotland E & S Livingstone1951;
Farreras Valenti  PVilaseca  JMDe Caralt  M Hereditary multiple diaphysial osteosclerosis of the Camurati-Engelmann type with leontiasis ossium syndrome [in Spanish]. Rev Esp Reumatol 1954;5 (6) 354- 362
PubMed
Fritsch  H Ein Fall von generalisierter osteosklerose. Wien Arch f inn Med 1932;23247- 256
Furia  JPSchwartz  HS Hereditary multiple diaphyseal sclerosis: a tumor simulator. Orthopedics 1990;13 (11) 1267- 1274
PubMed
Gelli  GPArioni  G Camurati-Engelmann multiple sclerosing hyperostotic osteopathy [in Italian]. Minerva Pediatr 1974;26 (15) 772- 778
PubMed
Gillespie  JBMussey  R Progressive diaphyseal dysplasia (Engelmann's disease). J Pediatr 1951;38 (1) 55- 59
PubMed
Goerke  H On another family with Camurati-Engelmann's disease (CEE) [in German]. Fortschr Geb Rontgenstr Nuklearmed 1960;92106- 109
PubMed
González Espinosa  CPerez Albelo  TCerrudo Hernández  RCHernández Gonzalez  JRFernández  JToledo Trujillo  F Progressive diaphyseal dysplasia with unusual bone involvement (Camurati-Engelmann disease) [in Spanish]. An Esp Pediatr 1991;34 (1) 71- 73
PubMed
Grey  ACWallace  RCrone  M Engelmann's disease: a 45-year follow-up. J Bone Joint Surg Br 1996;78 (3) 488- 491
PubMed
Griffiths  DL Engelmann's disease. J Bone Joint Surg Br 1956;38 (1) 312- 326
PubMed
Gulati  PDBhardwaj  OPVyas  PB Case of Englemann's disease. (With special plate) Br Med J 1967;3 (5559) 217
PubMed
Gulledge  WHWhite  JW Englemann's disease (progressive diaphyseal hyperostosis): report of a case. J Bone Joint Surg Am 1951;33 (3) 793- 797
PubMed
Gupta  SCheikh  IE Camurati-Engelmann disease in conjunction with hypogonadism. Endocr Pract 2005;11 (6) 399- 407
PubMed
Gvozdanovic  V New case of Engelmann's disease (congenital osteodystrophy) [in German]. Fortschr Geb Rontgenstr 1950;73 (1) 86- 89
PubMed
Hernández  MVPeris  PGuañabens  N  et al.  Biochemical markers of bone turnover in Camurati-Engelmann disease: a report on four cases in one family. Calcif Tissue Int 1997;61 (1) 48- 51
PubMed
Jackson  WPHanelin  JAlbright  F Metaphyseal dysplasia, epiphyseal dysplasia, diaphyseal dysplasia, and related conditions, III: progressive diaphyseal dysplasia. AMA Arch Intern Med 1954;94 (6) 902- 910
PubMed
Duclos  GJammes  AProuzet  JSerny  R Engelmann's disease: study of two familial cases [in French]. Presse Med 1956;24 (64) 1759- 1761
PubMed
Jammes  ASerny  RProuzet  JDuclos  G Engelmann's disease: hyperostotic and multiple sclerosing infantile osteopathy [in French]. Rev Rhum Mal Osteoartic 1953;20 (5) 406- 414
PubMed
Kormas  NDiamond  TShnier  R Camurati-Engelmann disease: two case reports describing metadiaphyseal dysplasia associated with cerebellar ataxia. J Bone Miner Res 1998;13 (7) 1203- 1207
PubMed
Kuhlencordt  FKruse  HPHellner  KAMontz  R Diaphyseal dysplasia (Camurati-Engelmann syndrome) with progressive loss of vision: 30-year observations and the effect of prednisolone treatment [author's translation] [in German]. Dtsch Med Wochenschr 1981;106 (19) 617- 621
PubMed
Lauterberg  W Uber zwei falle von familiarer generalisierter osteosklerose. Deutsche Ztschr f Chir 1931;230308- 315
Lavine  LSKoven  MT Engelmann's disease (progressive diaphyseal dysplasia). J Pediatr 1952;40 (2) 235- 239
PubMed
Lazzarone  CCartesegna  MCrova  MCalorio  D Progressive diaphyseal dysplasia: Camurati-Engelmann's disease. Ital J Orthop Traumatol 1983;9 (1) 109- 114
PubMed
LeBien  WEHeilman  C Progressive diaphyseal dysplasia: with report of a case. J Lancet 1951;71 (5) 189- 192
PubMed
Lelek  I Camurati-Engelmann disease [in German]. Fortschr Geb Rontgenstr Nuklearmed 1961;94702- 712
PubMed
Da Lima  LCRocha  M Engelmann's disease: progressive diaphyseal dysplasia [in Portuguese]. Rev Bras Cir 1952;24 (2) 281- 296
PubMed
Lücke  TIllsinger  SDas  AMSchirg  EHartmann  H Pitfalls in paediatric gait disturbances: painless bone diseases. Eur J Pediatr 2006;165 (12) 909- 912
PubMed
Lundy  MMBillingsley  JLRedwine  MDTurnbull  GLBrown  TJ Scintigraphic findings in progressive diaphyseal dysplasia. J Nucl Med 1982;23 (4) 324- 325
PubMed
Magnant  JSCampourcy  ABouville  J Engelmann's syndrome [in French]. J Chir (Paris) 1963;86293- 302
PubMed
Massé  GParenti  G Considerations on Camurati-Engelmann hereditary symmetrical osteopathia addensans [in Italian]. Arch Sci Med (Torino) 1966;122 (2) 92- 104
PubMed
Michaelis  LS Engelmann's disease. Proc R Soc Med 1949;42 (4) 271- 273
PubMed
Mikity  VGJacobson  G Progressive diaphyseal dysplasia (Engelmann's disease): report of a case with twenty-two–year follow-up. J Bone Joint Surg Am 1958;40 (1) 206- 210
PubMed
Mishra  GKMishra  MVernekar  JTehrai  MPatel  BR Progressive diaphyseal dysplasia: Engelmann's disease. Indian Pediatr 1987;24 (11) 1052- 1054
PubMed
Moudgil  AAgarwal  RKPati  HBagga  ASaraya  AK Camurati-Engelmann disease with recurrent bone marrow hypoplasia. Indian J Pediatr 1985;52 (415) 201- 204
PubMed
Narang  DBharati  BBhattacharya  AMittal  BR Radionuclide bone scintigraphy in Engelmann-Camurati disease. Arch Dis Child 2004;89 (8) 737
PubMed
Nelson  MScott  C Engelmann's disease (a form of craniodiaphyseal dysplasia). Birth Defects 1969;4301- 304
Neuhauser  EBSchwachman  HWittenborg  MCohen  J Progressive diaphyseal dysplasia. Radiology 1948;51 (1) 11- 22
PubMed
Newman  ATrunk  G Late roentgen sequelae of Engelmann's disease. Int Surg 1970;53 (1) 28- 32
PubMed
Nowicki  RWNorris  A Caesarean section in a patient with Engelmann's disease. Anaesthesia 1999;54 (11) 1118- 1119
PubMed
Ortolani  MCastagnari  G L’ostopatia di Camurati-Engelmann. Arch Putti Chir Organi Mov 1953;3146- 165
Panja  SChatterjee  SBasak  MChatterjee  R Progressive diaphyseal dysplasia (Camurati-Engelmann's disease). Indian Pediatr 1984;21 (8) 653- 655
PubMed
Patz  IM Engelmann's disease: case report and brief review. S Afr Med J 1960;34116- 119
PubMed
Perassi  F Camurati-Engelmann disease: sclerotic diaphysial symmetric hereditary hyperostosis [in Italian]. Radiol Med 1954;40 (2) 147- 159
PubMed
Raffaelli  PRonzini  MF Camurati-Engelmann's disease: a case report. Ital J Orthop Traumatol 1988;14 (2) 267- 271
PubMed
Ramanan  AVHall  MJBaildam  EMMughal  Z Camurati-Engelmann disease: a case report and literature review. Rheumatology (Oxford) 2005;44 (8) 1069- 1072
PubMed
Ribbing  S Hereditary, multiple, diaphyseal sclerosis. Acta Radiol 1949;31 (5-6) 522- 536
PubMed
Roth  J Hyperostosis generalisata, Camurati-Engelmann type. Harefuah 1957;52 (9) 223- 229
PubMed
Ruelle  MDubois  JL Apropos of 2 familial cases of multiple diaphyseal sclerosis (Camurati-Engelmann syndrome) [in French]. Rev Rhum Mal Osteoartic 1964;31345- 348
PubMed
Schollaert  EPouders  EMatton  PClaessens  HVan de Velde  E Diaphyseal dysplasia: late radiological discovery of 3 familial cases. J Belge Radiol 1983;66 (2) 93- 99
PubMed
Sear  HR Engelmann's disease: osteopathia hyperostotica sclerotisans multiplex infantilis: report of a case. Br J Radiol 1948;21 (245) 236- 241
PubMed
Shier  CKKrasicky  GAEllis  BIKottamasu  SR Ribbing's disease: radiographic-scintigraphic correlation and comparative analysis with Engelmann's disease. J Nucl Med 1987;28 (2) 244- 248
PubMed
Shuke  NTakashio  TYamamoto  W  et al.  Bone scintigraphy in a patient with progressive diaphyseal dysplasia. Clin Nucl Med 1997;22 (11) 791- 792
PubMed
Stegman  KFPeterson  JC Progressive hereditary diaphyseal dysplasia. Pediatrics 1957;20 (6) 966- 974
PubMed
Stenzler  SGrogan  DPFrenchman  SM McClelland  SOgden  JA Progressive diaphyseal dysplasia presenting as neuromuscular disease. J Pediatr Orthop 1989;9 (4) 463- 467
PubMed
Stewart  HBCole  ER Progressive diaphysial dysplasia (Englemann's disease). J Pediatr 1956;48 (4) 482- 485
PubMed
Stirpe  M Exophthalmos and convergence insufficiency in Camurati-Engelmann disease [in Italian]. Boll Ocul 1965;44 (9) 625- 646
PubMed
Stronge  R McDowell  H A case of Engelmann's disease progressive diaphysial dysplasia. J Bone Joint Surg Br 1950;32 (1) 38- 39
Sty  JRBabbitt  DPStarshak  RJ Bone scintigraphy demonstrating Engelmann's disease. Clin Nucl Med 1978;3 (2) 69- 70
PubMed
Verbruggen  LABossuyt  ASchreuer  RSomers  G Clinical and scintigraphic evaluation of corticosteroid treatment in a case of progressive diaphyseal dysplasia. J Rheumatol 1985;12 (4) 809- 813
PubMed
Viviani  G A case of Camurati-Engelmann disease [in Italian]. Ann Radiol Diagn (Bologna) 1960;33340- 352
PubMed
Weingraber  H A new observation in a case of osteopathia hyperostotica Engelmann-Camurati [in German]. Fortschr Geb Rontgenstr 1954;81 (6) 800- 804
PubMed
Whyte  MP Heritable metabolic and dysplastic bone diseases. Endocrinol Metab Clin North Am 1990;19 (1) 133- 173
PubMed
Wiedemann  H Systematisierte sklerotische Hyperostose des Kindesalters mit Myopathie. Ztschr f Kinderheilk 1948;65346- 347
Willems  DVerhelst  MMulier  JCMartens  M Engelmann's disease: report of four cases with review of literature. J Belge Radiol 1973;56 (5) 395- 398
PubMed
Wu  SLiang  SYan  Y  et al.  A novel mutation of TGFβ1 in a Chinese family with Camurati-Engelmann disease. Bone 2007;40 (6) 1630- 1634
PubMed
Yvars  MF Engelmann's disease: a case report. Clin Orthop Relat Res 1969;62206- 208
PubMed
Beighton  PDurr  LHamersma  H The clinical features of sclerosteosis: a review of the manifestations in twenty-five affected individuals. Ann Intern Med 1976;84 (4) 393- 397
PubMed
Saraiva  JM Anticipation in progressive diaphyseal dysplasia. J Med Genet 2000;37 (5) 394- 395
PubMed
Kirkpatrick  DBRimoin  DLKaitila  IGoodman  SJ The craniotubular bone modeling disorders: a neurosurgical introduction to rare skeletal dysplasias with cranial nerve compression. Surg Neurol 1977;7 (4) 221- 232
PubMed
Shelton  CLuxford  WMTonokawa  LLLo  WWHouse  WF The narrow internal auditory canal in children: a contraindication to cochlear implants. Otolaryngol Head Neck Surg 1989;100 (3) 227- 231
PubMed
Hamersma  HMay  MOsteopetrosis and Facial Palsy: The Facial Nerve. 2nd ed. New York, NY Thieme Inc2000;409- 421
Hamersma  H Total decompression of the facial nerve in osteopetrosis (marble bone disease-morbus Albers-Schönberg). ORL J Otorhinolaryngol Relat Spec 1974;36 (1) 21- 32
PubMed

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 6

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Skull base manifestations of Camurati-Engelmann disease. Arch Otolaryngol Head Neck Surg 2010;136(6):566-75.