CASE REPORTS
J Oral Maxillofac Surg
Cherubism: Clinicoradiographic Features,
Treatment, and Long-Term Follow-Up
of 8 Cases
Edgard Carvalho Silva, DDS, PhD,*
Guilherme Costa Carvalho Silva, DDS,†
and Tainah Couto Vieira, DDS‡
Cherubism is a rare non-neoplastic hereditary disease
related to genetic mutations characterized by bilateral
bone enlargement of the jaws in childhood. Docu-
mented long-term follow-up of a series of cases is
presented. Four familial and 4 sporadic cases of
cherubism have been treated and followed for a mean
of 18 years (range, 5 to 32 years). Four of the patients
were subjected to cosmetic surgical correction justi-
fied by extreme size of the jaws, whereas the other 4
underwent just biopsy or ectopic and impacted teeth
removal. Fibro-osseous lesions spontaneously re-
gressed at different levels at variable time intervals.
Apparent radiographic osseous repair occurred rou-
tinely. In adult life, the patients exhibited normal
facial appearance, and radiographs showed almost
complete involution of the lesions. Long-term fol-
low-up of these patients is desirable to evaluate pro-
gression or involution of the lesions. Apparently, sur-
gical intervention is unnecessary unless significant
functional, esthetic, or emotional disturbances de-
velop.
Cherubism, first described by Jones,1 is a benign,
self-limiting fibro-osseous disorder characterized by
bilateral expansion of the mandible, maxilla, or both.
The lesions are usually symmetrical and painless. Fre-
Received from the School of Dentistry, Federal University of Minas
Gerais, Belo Horizonte, Brasil.
*Emeritus and Titular Professor, Department of Oral Surgery and
Pathology.
†Resident, Department of Oral Surgery and Pathology.
‡Resident, Department of Pediatric Dentistry and Orthodontics.
Address correspondence and reprint requests to Dr G. Carvalho
Silva: Universidade Federal de Minas Gerais, Faculdade de Odonto-
logia, Departamento de Clínica, Patologia e Cirurgia, Av Antônio
Carlos 6627, 31270-901, Belo Horizonte, MG, Brasil; e-mail:
oguila@terra.com.br
© 2007 American Association of Oral and Maxillofacial Surgeons
0278-2391/07/6503-0023$32.00/0
doi:10.1016/j.joms.2006.05.061
517
65:517-522, 2007
quently, cherubism is accompanied by dental arch
and dental eruption abnormalities. Extragnathic skel-
etal involvement is rare. The rounded facies and oc-
casional upward cast of the eyes with exposure of the
sclerae below the pupil give the patient an appear-
ance reminiscent of the cherubs portrayed in Renais-
sance paintings. Affected children appear normal at
birth and are mentally normal. Jaw expansion is no-
ticed within the first years of life, becoming progres-
sively larger until puberty. Lesion regression is ex-
pected to occur spontaneously by the end of
adolescence, resolving by middle age.1
Radiographically, lesions appear as cystic multiloc-
ular radiolucencies, often beginning near the angle of
the mandible and spreading to the mandibular ramus
and body. Maxillary lesions may occur at the same
time. Frequently, ectopic unerupted teeth are in-
volved by lesions.1-13
The histology is limited for diagnosis, showing fi-
brous hyperplasia and multinucleated giant cells.
These features are similar to those other bone dis-
eases such as brown tumor of hyperparathyroidism,
giant cell tumor, and central and peripheral giant cell
granuloma.2-6,8-10,13
Cherubism is a familial disease1-9 in which the trait
is transmitted in an autosomal dominant fashion with
100% penetrance in males and 50% to 70% penetrance
in females.4 However, several isolated cases have
been reported in the literature.7,9,11-13 Novel muta-
tions in the gene encoding the binding protein
SH3BP2 on chromosome 4p16.3 have been reported
to cause cherubism.14-16
Studies of cherubism with long-term follow-up
presenting with clinicoradiographic documenta-
tion clearly demonstrating spontaneous resolution
of bone lesions are extremely rare in the literature.
Here we report 8 cases of cherubism, 4 cases from
the same family and 4 nonfamilial sporadic cases,
followed up for a mean of 18 years. We discuss
disease behavior, treatment approaches, and clini-
coradiographic aspects.
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Report of Cases
CASE 1
Patient 1, a boy, presented with painless facial swelling at
age 6 years. Extraoral radiographs showed transparent mul-
tilocular lesions completely involving the maxilla and man-
dible. Maxillary sinuses were not visible. Medical and family
histories were unremarkable. With a clinicoradiographic di-
agnosis of cherubism, the patient was scheduled for regular
follow-up. By age 10, mandibular enlargement became more
noticeable; this persisted until age 12, when the lesions began
to decrease. At age 16, mandibular enlargement was minor,
with swelling more noticeable in the maxilla; radiographs
exhibited significant remission of radiolucent areas, and the
maxillary sinuses were clear. At age 25, the patient exhib-
ited slight swelling of the maxilla, and a panoramic radio-
graph showed multilocular lesions almost totally filled in
with bone (Fig 1).
FIGURE 1. Patient 1. A, At age 6 years, the patient exhibited facial
bilateral enlargement, and a lateral radiograph showed multilocular
transparencies involving the jaws. The maxillary sinuses were not
visible. Increased facial enlargement was seen at age 10 years (B)
and also at 11 years (C). D, At 16 years, minor expansion of the
mandibule and more maxillary enlargement were observed. A radio-
graph revealed clear maxillary sinuses and significant remission of the
radiolucent areas, with a thin mandibular border. E, At age 25, the
patient had only slight swelling of the maxilla, and a panoramic
radiograph showed the jaws almost totally filled in with bone. The
mandibular border was thicker and evident.
Carvalho Silva et al. Cherubism. J Oral Maxillofac Surg 2007.
CHERUBISM
FIGURE 2. Patient 2. A, At age 15 years, the patient showed
mandibular bilateral enlargement. B, A panoramic radiograph
showed the mandible filled with multilocular transparent lesions. C,
Mandibular occlusal radiographs showed evident bone filling in the
anterior region 1 year after the previous radiograph.
Carvalho Silva et al. Cherubism. J Oral Maxillofac Surg 2007.
CASE 2
Patient 2, a girl, presented with bilateral painless swelling
of the mandible at age 15. Her medical and family histories
were unremarkable. Radiographs revealed multilocular ar-
eas involving the mandible. Biopsy findings confirmed a
diagnosis of cherubism. Treatment involved regular fol-
low-up visits. One year later, an occlusal radiograph showed
outstanding osseous repair in the anterior portion of
the mandible (Fig 2). Over the subsequent years, disease
regression was observed. The patient was lost to follow-up
at age 20.
CASE 3
Patient 3, a boy, exhibited discrete painless growth of the
face at age 6 years. A panoramic radiograph showed mul-
tilocular areas in mandibule and maxilla. No familial cases
were reported. Biopsy findings confirmed a diagnosis of
cherubism, and the patient was scheduled for regular fol-
low-up. By age 12, the patient’s condition began to regress.
At age 21, he returned for extraction of ectopic and une-
rupted teeth, at which time swelling was found to be
constricted to the maxilla. Two years later, his remaining
teeth required extraction. At this time, minor residual en-
largement in the maxilla was seen, and a radiograph showed
significant bone filling over the multilocular areas (Fig 3).
CASE 4
In patient 4, a boy, facial alteration was first noted at age 4
years and progressively developed asymptomatically. At age
12, the patient showed enlargement of the jaws, most notice-
able on the right side. Panoramic radiograph showed mul-
tilocular areas involving the jaws. Family history was
negative for cherubism. In the subsequent year, the pa-
tient underwent minor surgeries for removal of the upper
right second premolar and biopsy, which confirmed the
clinical diagnosis of cherubism. At age 14, a small corrective
approach was performed in the right body of the mandible,
simultaneously with extraction of the lower right second
premolar. At age 20, the patient had a harmonic face, and a
panoramic radiograph showed bone filling into radiolucent
areas (Fig 4).
CASE 5
In patient 5, facial swelling noted at age 10 years was
diagnosed as cherubism by a colleague. The patient was lost
from follow-up. According to the patient, at age 18, resec-
tive surgery was performed in the right body of the mandi-
ble due to a misdiagnosis of ameloblastoma. At age 39, the
CARVALHO SILVA ET AL 519

patient had a normal face, and a panoramic radiograph

showed only residual mandibular radiolucencies (Fig 5).

CASE 6
Patient 6, the son of patient 5, was diagnosed with
cherubism at age 6 years due to cheek enlargement and
family history. A panoramic radiograph at age 9 showed
multilocular transparencies completely occupying the man-
dible and maxilla. At age 13, painless bilateral jaw expan-
sion was noted, and a radiograph showed remaining mul-
tilocular areas. Minor signs of osseous repair were observed
in the mandibular ramus. Three minor surgeries were exe-
cuted in the following 3 years for biopsy (which confirmed
the diagnosis), for extraction of displaced and impacted
teeth (upper right second molar and premolar; lower left
canine and first and third molars; lower right canine, second
premolar, and first and third molars), and in an attempt to
provide orthodontically assisted eruption of unerupted up-
FIGURE 4. Patient 4. A, At age 12, the patient exhibited facial
per left central incisor. At age 16, changes in cystic lesions
swelling, more pronounced on the right side. A radiograph showed a
were observed (Fig 6). few well-delimited multilocular lesions involving the mandible and
affecting only the tuberosities in the maxilla. A sclerotic area was seen
CASE 7 below the lower right first molar, along with root resorption in this tooth.
Patient 7, a sister of patient 5, exhibited bilateral painless B, At age 20, facial appearance was close to normal, and a pan-
oramic radiograph showed remission of transparent lesions in all but
facial expansion at age 8 years. At age 11, the facial growth
the anterior portion of the mandible. No maxillary involvement was
stopped, and corrective surgery was done in the left body of seen. Successful orthodontic treatment was carried out. Note the bone
the mandible. No further enlargement was observed until filling in the left coronoid process compared with the initial radiograph.
age 15, when residual jaw expansion began to regress. At
Carvalho Silva et al. Cherubism. J Oral Maxillofac Surg 2007.

age 40, the patient’s face was normal. A radiograph revealed

typical radiopacity of bone structures in the maxilla. In the
mandible, a radiograph showed residual multilocular trans-
parencies in the coronoid processes and in the mandibular
ascending rami, along with some sclerotic areas in the
mandibular body (Fig 7).

CASE 8
Patient 8, a daughter of patient 7, was diagnosed with
cherubism at age 5, based on painless facial enlargement
and family history. A lateral extraoral radiograph showed
multilocular radiolucencies in the jaws. Enlargement of the
jaws persisted until age 9. Histological examination of an
incisional biopsy specimen confirmed the diagnosis. At age
13, the patient demonstrated noticeable bilateral swelling of
the jaws, and a radiograph showed persistent complete
involvement of the jaws by the lesions, with a prominence
in the right mandibular body. Four years later, involvement
of the mandible and maxilla remained considerable, and

FIGURE 3. Patient 3. A, At age 6, the patient exhibited facial

enlargement. A panoramic radiograph showed multilocular radiolu-
cencies with diffuse jaw involvement. Note the large radiolucency in
the right mandibular body. B, At age 21, facial swelling was restricted
to the maxilla, and a radiograph revealed impaction of the inferior
anterior teeth, as well as teeth abnormalities. Regression of multilocular
lesions was noticeable. C, At age 23, facial appearance was similar
to the previous condition, and a radiograph showed almost complete
regression of the lesions. Note the total bone filling in the large lesion
observed at age 6 in the right body of the mandible.
Carvalho Silva et al. Cherubism. J Oral Maxillofac Surg 2007.
FIGURE 5. Patient 5. At age 39, facial appearance was normal. A
panoramic radiograph showed normal maxilla and sclerotic areas
near the apex of the lower left second molar. At age 18, a hemiman-
dibulectomy was performed in the right side of the mandible due to an
incorrect diagnosis of ameloblastoma.
Carvalho Silva et al. Cherubism. J Oral Maxillofac Surg 2007.
520
FIGURE 6. Patient 6. A, At age 9, a panoramic radiograph showed
multilocular cystic lesions involving maxilla and mandibule. B, At age
13, mandibular enlargement was evident, and a radiograph showed
ectopic, unerupted teeth and complete filling of the mandible and
maxilla by multilocular transparent lesions. C, At 16 years, mandibular
swelling was persistent, and a panoramic radiograph revealed fewer
but larger cystic lesions compared with previous findings.
Carvalho Silva et al. Cherubism. J Oral Maxillofac Surg 2007.
corrective surgery was executed in the right angle and body
of the mandible. Three years after the operation, diminished
right mandibular swelling was seen (Fig 8).
Discussion
Several family studies from different countries have
postulated that cherubism is a hereditary condi-
tion,1-10 transmitted in an autosomal dominant pat-
tern.4 A molecular pathogenesis of cherubism has
been proposed: SH3BP2 gene mutations cause dys-
regulation of the Msx-1 gene, which is involved in
FIGURE 7. Patient 7. At age 40, the face appears normal. A
panoramic radiograph revealed residual radiolucencies in the coro-
noid processes and in the ascending rami, as well as sclerotic areas
in the body of the mandible.
Carvalho Silva et al. Cherubism. J Oral Maxillofac Surg 2007.
CHERUBISM
FIGURE 8. Patient 8. A, At age 5, a lateral radiograph showed
multilocular lesions occupying the jaws. B, At age 13, a panoramic
radiograph showed diffuse, transparent multilocular lesions in the
jaws. Ectopic, impacted, and missing teeth, as well as root resorption
in the lower right first molar, were also observed. C, At age 17, facial
enlargement was more pronounced on the right side. A radiograph
showed persistent multilocular lesions, with some discrete sclerotic
areas. D, At age 20, decreased facial enlargement on the right side
was evident after corrective surgery. A radiograph still revealed mul-
tilocular lesions, however. Note the progression of bone filling in the
left angle of the mandible, compared with previous radiographs.
Carvalho Silva et al. Cherubism. J Oral Maxillofac Surg 2007.
regulating mesenchymal interaction in craniofacial
morphogenesis. In an affected individual, increased
bone activity occurs between age 2.5 and 10 to 12
years, due to up-regulation of Msx-1. Dysfunction of
Msx-1 stops at the end of molar development, leading
to remineralization of lesions.16
Isolated single cases of cherubism have been re-
ported in the literature,7,9,11-13 most of them based on
historic reports of the affected family members, who
had not noticed any facial alteration in other relatives.
It is difficult to assess whether these cases represent
spontaneous mutations, because of cherubism’s vari-
able expression and its tendency to resolve. In addi-
tion, the autosomal recessive pattern was suggested
to occur in selected families.8 In our nonfamilial
cases, beyond the historic data provided by the pa-
tients’ parents, we observed close relatives for cheru-
bic features; however, we cannot affirm that these
cases are examples of pure mutations.
In general, cherubism does not affect other parts of
the skeleton or osseous metabolism; the bone mark-
ers phosphorous, serum calcium, and alkaline phos-
CARVALHO SILVA ET AL 521

Table 1. PATIENTS’ GENDER, AGE AT DIAGNOSIS, TYPE OF INTERVENTION, AND FOLLOW-UP PERIOD

Follow-Up
Patient Gender Age (yrs) Classification Intervention (yrs)

1 (Fig 1) M 6 Grade 3 Biopsy and impacted teeth removal 19

2 (Fig 2) F 15 Grade 1 Biopsy 5
3 (Fig 3) M 6 Grade 3 Biopsy and impacted teeth removal 17
4 (Fig 4) M 4 Grade 2 Biopsy, impacted teeth removal, and minor corrective surgery 16
in the right body of the mandible
5 (Fig 5) F 10 Grade 3 Biopsy, impacted teeth removal, and resective surgery in the 29
right body of the mandible
6 (Fig 6) M 6 Grade 3 Biopsy and impacted teeth removal 10
7 (Fig 7) F 8 Grade 3 Biopsy, impacted teeth removal, and corrective surgery in the 32
right body of the mandible
8 (Fig 8) F 4 Grade 3 Biopsy, impacted teeth removal, and corrective surgery in the 16
right angle of the mandible
Carvalho Silva et al. Cherubism. J Oral Maxillofac Surg 2007.

phatase are usually at normal levels with respect to
age.2,5,10,12,13,17,18 Significant ocular disturbances,
such as proptosis, superior globe displacement, and
visual loss, may occur,19 although these were not
observed in our cases. Patients 1, 6, and 8 showed
exposure of the inferior part of the sclerae, confirm-
ing that this characteristic is occasional.4,7-9 Some
studies have suggested that cherubism may be asso-
ciated with other genetic diseases, such as Noonan’s
syndrome20,21 and Ramon syndrome.22,23 An associa-
tion with gingival fibromatosis also has been postu-
lated.24 Aggressive manifestations of cherubism have
been reported,6,12,25 including 1 extreme case that
progressed rapidly, resulting in death due to gastroin-
testinal and pulmonary infections.26
In cherubism, the initial facial alteration becomes
apparent in the first years of life.1-5,7-11,13 We cannot
precisely affirm when facial swelling was first noticed
in all of our patients, because they were first exam-
ined at different ages, ranging from 4 to 15 years. In
the older patients, signs of cherubism likely were
present well before the patients came to us.
The clinical aspects and disease course observed in
our patients were similar to those in previous stud-
ies,1-5,7-11 as were the histological features.1,2,4,5,8-11,13
All of the patients that we followed presented with
painless bilateral lesions. Radiographically, these le-
sions appeared as multilocular cystic radiolucencies
involving the jaws in all patients but patient 2, who
exhibited mandibular association but no maxillary
involvement. Because this patient was first seen at age
15, we cannot verify that she never had any maxillary
alteration. Abnormal patterns of teeth eruption were
noted in all cases, as well as teeth agenesis and the
presence of ectopic or retained teeth. On average, the
disease manifested in childhood, stabilized by age 12
years, and began to regress during puberty. Bone
recontouring continued through the third decade of
life, and the face alteration disappeared. This course
was observed in all patients except patient 8, who at
age 20 still manifested clinicoradiographic features of
cherubism. The remission of facial bone enlargement
seemed to occur later in the maxilla than in the
mandible. Radiographic follow-up showed that mul-
tilocular radiolucent areas gradually filled in with os-
seous structure, sometimes within a short period, as
seen in patient 2. Sclerotic areas replaced radiolucent
multilocular regions even in the 2 familial cases (pa-
tients 5 and 7) in the fifth decade of life, in contrast to
the conclusion of another study7 asserting that scle-
rotic areas have been described only in single cases.
The histological appearance was similar to that of
brown tumor of hyperparathyroidism, giant cell tu-
mor, and central and peripheral giant cell granuloma,
consisting of proliferating vascular fibrous connective
tissue with abundant multinucleated giant cells. In
adult patients, this tissue showed an increase of bone
matrix in fibrous stroma.
Seward and Hankey3 suggested a grading system for
cherubism that has been since modified by other
authors.6,7,9 According to the classical grading system
based on the radiographic location of the lesions, 6 of
our 8 patients were grade 3 (both jaws diffusely af-
fected); 1 patient (patient 2) was grade 1, with man-
dibular but no maxillary involvement at the time of
examination; and 1 patient (patient 4) was grade 2,
with full mandibular involvement and maxillary in-
volvement only in the tuberosities. Remission of signs
of cherubism occurs most rapidly in grade 1 (lesions
restricted to posterior regions of the mandible).7 We
found that the lesions regressed progressively even in
the patients with grade 3, both those who underwent
surgery and those who did not, and in adulthood
these patients had normal or close to normal facial
and radiographic aspects, sometimes with minor re-
sidual marks.
522
Conventional surgical procedures for biopsy or im-
pacted teeth removal were used in all cases (Table 1).
In the 4 patients who exhibited significant increase in
the jaws, corrective osteoplasty was performed, pro-
ducing marked reduction of facial deformities with no
recurrence. Consider the case of patient 5, who was
lost to follow-up and underwent a hemimandibulec-
tomy due to an incorrect diagnosis of ameloblastoma
but even so exhibited remission of cherubic charac-
teristics in adulthood. Traditionally, the general ap-
proach to treating cherubism was to follow patients,
perform biopsies, remove ectopic and impacted
teeth, and provide surgical correction when appropri-
ate.3-5,7-9,11,17 Liposuction has been proposed to re-
duce the mass of the lesion in particular cases.27
When discussing treatment, we must consider the
psychological problems associated with an unattrac-
tive cherubic appearance in young patients. The 4
patients who underwent surgery for osseous contour-
ing had deformities caused by large bone expansion,
mainly in the mandible.
Findings showed that the multinucleated cells in
cherubic lesions were osteoclasts from a structural
and biochemical standpoint,10 raising the possibility
of treatment with calcitonin, reducing the need for
surgery in cases with significant expansion. Calcito-
nin has been used successfully for treatment of giant
cell granuloma,28,29 and it has reduced bone absorp-
tion of cherubic osteoclasts in vitro.10 Based on the
genetic mutations related to the disease,14-16 gene
therapy is expected to play a role in future treatment.
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