Cherubism: Clinicoradiographic Features and Treatment

Cherubism is a congenital childhood disease of autosomal dominant inheritance. This disease is characterized by painless bilateral enlargement of the jaws, in which bone is replaced with fibrous tissue. The condition has sui generis clinical, radiographic and histological features, of which the clinician should be aware for a better differential diagnosis in the presence of a fibro-osseous lesion affecting the bones of the maxillomandibular complex. The purpose of present paper was to review the literature and to report the most important aspects of cherubism in order to facilitate the study of this disease Material and Methods Literature was reviewed about cherubism, emphasizing the relevant clinicoradiographic features and treatment. Literature was selected through a search of PubMed and Scielo electronic databases. The keywords used for search were adolescent, cherubism, cherubism/physiopathology, cherubism/treatment, cherubism/radiography. A manual search of the reference lists of the identified articles and the authors' article files and recent reviews was conducted to identify additional publications. Those studies that described new features about cherubism were included in this review.  In total 44 literature sources were obtained and reviewed. Studies that described new features about cherubism physiopathology, diagnostics and treatment were reviewed.  Despite the exceptions, cherubism is a clinically well-characterized disease. In cases of a suspicion of cherubism, radiographic examination is essential since the clinical presentation, the location and distribution of the lesions may define the diagnosis. Histopathological examination is complementary. Nowadays, genetic tests should be used for final diagnosis of cherubism.

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title: Cherubism--clinical picture and treatment.
abstract: Cherubism is a rare, painless, disfigurating disease primarily affecting bones of the jaws.



To report on five patients with cherubism. The symptoms of the disease, methods of management and possible mode of inheritance are discussed and literature is reviewed.



The study involves five cherubs, members of one family. The diagnoses were based on history, physical examination, laboratory tests, X-ray parameters, and clinical follow-up. One member of the family had surgical intervention. The remaining cases were left for observation.



Good aesthetic and long lasting effect was reached in the operated patient.



Treatment is unnecessary unless functional or emotional disturbances develop. An autosomal recessive pattern of inheritance is suggested for these cases, although autosomal dominant transmission has been previously established.

title: A novel mutation in the SH3BP2 gene causes cherubism: case report
abstract: BackgroundCherubism is a rare hereditary multi-cystic disease of the jaws, characterized by its typical appearance in early childhood, and stabilization and remission after puberty. It is genetically transmitted in an autosomal dominant fashion and the gene coding for SH3-binding protein 2 (SH3BP2) may be involved.Case presentationWe investigated a family consisting of 21 members with 3 female affected individuals with cherubism from Northern China. Of these 21 family members, 17 were recruited for the genetic analysis. We conducted the direct sequence analysis of the SH3BP2 gene among these 17 family members. A disease-causing mutation was identified in exon 9 of the gene. It was an A1517G base change, which leads to a D419G amino acid substitution.ConclusionTo our knowledge, the A1517G mutation has not been reported previously in cherubism. This finding is novel.

title: Non-familial cherubism.
abstract: Cherubism is a disease that usually affects the jaws in the paediatric population, mostly below five years of age. Radiologically, it closely resembles fibrous dysplasia and other giant cell lesions of the mandible. Computed tomography (CT) is helpful in defining the true extent of cherubic lesions, which is often not possible on radiographs due to the overlapping facial bones. We describe the radiographical and CT features of cherubism in a 12-year-old boy and highlight the ability of multidetector CT and various post-processing techniques to accurately depict the anatomical extent of the cherubic lesions.

title: Aggressive case of cherubism: 17-year follow-up.
abstract: Cherubism is an autosomal dominant disorder in which the normal bone is replaced by cellular fibrous and immature bone, resulting in painless symmetrical enlargement of the jaws. An aggressive case of cherubism with extensive swelling on several facial bones in a 19-year-old boy is reported. The disorder was diagnosed 15 years ago, but the patient has not been submitted to any type of surgery so far. The highlights of this case are the great proportion of the lesions, the enormous functional and emotional disturbances brought about by these lesions, and the difficulty to choose the most appropriate age and form of treatment.

title: Imaging characteristics of cherubism.
abstract: We sought to describe the radiographic and imaging features of cherubism.



Cherubism is a rare osseous disorder of children and adolescents. Although the radiologic characteristics of cherubism are not pathognomonic, the diagnosis is strongly suggested by bilateral relatively symmetric jaw involvement that is limited to the maxilla and mandible. Imaging typically shows expansile remodeling of the involved bones, thinning of the cortexes, and multilocular radiolucencies with a coarse trabecular pattern.

title: Cherubism in siblings: a case report.
abstract: Cherubism is a non-neoplastic bone disease characterized by clinically evident bilateral, painless enlargements of the jaws that are said to give the patient a cherubic appearance. Cherubism may appear in solitary cases or in many members of the same family, often in multiple generations. On radiography, the lesions exhibit bilateral multilocular radiolucent areas. Histopathologic evaluation reveals proliferating fibrous connective tissue containing numerous multinucleated giant cells. Since the first description of this condition in 1933, almost 200 cases have been reported. We describe cherubism in 2 siblings and briefly review the literature on this subject.

title: Cherubism: long-term follow-up of 2 patients in whom it regressed without treatment.
abstract: Cherubism is a rare hereditary, self-limiting fibrous dysplasia characterised by painless enlargement of the jaws in childhood. Although, it is accepted that the lesions of cherubism are eventually replaced by bone, there have been few long-term follow-up reports with clinicoradiographic documentation of spontaneous remission of the disease, without treatment. We report two cases of cherubic boys who were followed for 17 and 19 years. Clinicoradiographic examination during this period showed regression of the disease without surgical correction.

title: Study of the cell biology and biochemistry of cherubism.
abstract: To establish whether the multinucleate cells in lesions of patients with cherubism are also osteoclasts and if this is the case whether they were responsive to calcitonin; to carry out cytogenetic studies on two members of the same family affected by cherubism in an attempt to identify any major chromosomal defects; and to perform an in-depth modern biochemical study of four children in the same family.  Four related children with cherubism were studied. Tissue taken from one of the children at elective decompression of an optic nerve was submitted to in vitro bone resorption studies. Cytogenetic studies were done on two of the children and biochemical studies on all four.  The multinucleate cells in the cherubic lesions were shown to be osteoclasts since they synthesised tartrate resistant acid phosphatase, expressed the vitronectin receptor, and resorbed bone. Bone resorption by the cultured multinucleate cells was significantly inhibited by calcitonin. High resolution cytogenetic studies failed to detect any chromosomal abnormalities in two children with cherubism. The biochemistry profile of all four children with cherubism showed that serum calcium, parathyroid hormone, parathyroid related hormone, calcitonin, and alkaline phosphatase were within normal levels. Urine analysis of pyridinium and deoxypyridinium cross links, hydroxyproline, and calcium in relation to urine creatinine were measured to assess bone resorption in these children, and the values were at the upper end of the normal range in all four.  Further studies are required to determine whether calcitonin treatment will control this grossly deforming disease until the time when the physiological changes that occur at puberty rectify the pathology. It is not recommended that biochemical markers of bone resorption are used in isolation to monitor the activity of cherubism in individuals because the results are based on a small number of children and because of reports of marked interindividual variation in the levels of these markers, particularly in children.

title: An extreme case of cherubism.
abstract: We describe an 8-year-old boy who presented with severe facial swelling. This progressed rapidly and 17 months later he died of gastrointestinal and pulmonary infections. The diagnosis was initially brown tumour associated with hyperparathyroidism, but this was revised in the light of laboratory investigations that were within the reference ranges, and normal appearance of the parathyroids on exploration to that of an extreme case of cherubism that behaved in a locally aggressive manner.

title: Aggressive behaviour of cherubism in a teenager: 4-years of clinical follow-up associated with radiographic and histological features.
abstract: Cherubism is a rare hereditary fibro-osseous childhood disease characterized by bone degradation and fibrous tissue replacement at the angles of the mandible and at the tuberosity areas of the maxilla that leads to prominence of the lower face and an appearance reminiscent of the cherub's portrayal in Renaissance art. This disease has an autosomal dominant hereditary characteristic. The purpose of this report is to analyse laboratory tests, clinicopathological and radiographic features of cherubism and its intraoral manifestations in a patient during 4-years of follow-up, correlating the features observed in this case with those of the literature. Also discussed is the atypical and aggressive behaviour of this case during puberty.

title: Diagnosis and Treatment of Familial Cherubism Characterized by Early Onset and Rapid Development
abstract: Cherubism is a benign maxillary bone dysplasia of childhood, usually showing an autosomically dominant inheritance with variable penetrance and spontaneously resolving after puberty. Only maxillary bones are affected and develop pseudocystic osteolytic lesions. This article presents an early and rapidly evolving familial case of cherubism. The 3-year-old child underwent conservative curettage of lesions, with a conservative approach that allowed a normal permanent dentition in adolescence. Family history revealed that the father had been treated for similar lesions between 14 and 21 years of age, but the late treatment caused edentulism. In conclusion, although cherubism represents a benign and localized maxillary dysplasia, it requires prompt surgical but conservative treatment and careful follow-up to avoid permanent lesions, that is, malocclusion and/or edentulism.

title: Cherubism and its charlatans.
abstract: Cherubism is a rare hereditary condition characterised by progressive cystic proliferation of the mandible and maxilla in childhood, followed by post-pubertal involution of the process and jaw remodelling in adulthood. Its name is derived from the cherubic appearance that results from the jaw hypertrophy. Here, we present the case of a young boy with cherubism, in the context of his pedigree, to illustrate the clinical characteristics and their variable expression. We also seek to distinguish cherubism from central giant cell granuloma and giant cell tumour of the jaws, with which it holds a false synonymity.

title: Adaptor protein 3BP2 and cherubism.
abstract: The adaptor protein 3BP2 (c-Abl Src homology 3 domain-binding protein-2, also referred to SH3BP2) is known to play a regulatory role in signaling from immunoreceptors. In mast cells, 3BP2 is rapidly tyrosine phosphorylated by the aggregation of the high affinity IgE receptor and the overexpression of its SH2 domain results in the dramatic suppression of IgE-mediated tyrosine phosphorylation of PLC-alpha, Ca2+ mobilization and degranulation. 3BP2 is a substrate of the protein-tyrosine kinase Syk, which phosphorylates it on Tyr174, Tyr183, and Tyr446 (in the mouse protein). Phosphorylation of Tyr183 promotes the activation of Rac1 through the interaction with the SH2 domain of Vav1. Phosphorylation of Tyr446 induces the binding to the SH2 domain of the upstream protein-tyrosine kinase Lyn and enhances its kinase activity. Thus, 3BP2 has a positive regulatory role in IgE-mediated mast cell activation. In lymphocytes, engagement of T cell or B cell receptors triggers tyrosine phosphorylation of 3BP2. Suppression of the 3BP2 expression by siRNA results in the inhibition of T cell or B cell receptor-mediated activation of NFAT. Genetic analyses reveal that 3BP2 is required for the proliferation of B cells and B cell receptor signaling. Point mutations of the 3BP2 gene cause the rare human inherited disorder cherubism, characterized by excessive bone resorption in the jaw bones. These mutations include substitution and deletion mutations of 3BP2. "Cherubism" mice exhibit increased myeloid cell responses to M-CSF and RANKL leading to the activation of osteoclasts. Further analysis could demonstrate that inhibition of 3BP2 might have therapeutic potential.

title: Familial cherubism: the experience of the Moscow Central Institute for Stomatology and Maxillo-Facial Surgery.
abstract: The Central Institute for Stomatology and Maxillo-facial Surgery in Moscow is one the main centers for the treatment of pediatric head and neck tumors in the territory of the former Soviet Union. A series of 33 patients presenting with cherubism (24 children and 9 of their parents) is presented. The authors discuss the atypical clinical presentations, the relevant associated anomalies and the different treatment strategies. They report the first case of cherubism associated with gingival hypertrophy without neurological signs.

title: Cherubism: clinical evidence and therapy.
abstract: Cherubism is a hereditary childhood disease of autosomal dominant inheritance that is more common in the male sex. Some cases have also revealed a mutation of the gene FGF-RIII (fibroblast growth factor receptor III). The clinical picture of cherubism is characterized by painless symmetrical swelling of the mandible and polycystic destruction of the mandibular bone structure. Complications include delayed dentition, dental root resorption, malalignment of teeth, and impacted teeth. The disease progression comes to a halt of its own accord at the end of puberty. Spontaneous recoveries have been observed. Histologically, multinuclear giant cells with osteoclastic activity, which correspond to a giant cell granuloma, are found in fibrous stroma. It is generally agreed that decisions about surgical intervention should be considered carefully. A case report describes the course of the disease and therapy of a female patient with a periorbital manifestation of cherubism. The latero-orbital enlargement of the intraorbital and latero-orbital region of the zygomatic bone resulted in displacement of the orbital contents with a motility disorder of the eyes. The motility disorder was eliminated by reduction of the diseased hard tissue as well as by carrying out a modeling orbitotomy and by reconstructing an anatomically correct localized and irregular bilateral osseous structure of the zygomatic bone in the intraorbital and latero-orbital region.

title: Clinical and radiological evaluation of cherubism: a sporadic case report and review of the literature.
abstract: Many cases have been published on cherubism since Jones described it first time in three children of the same family [ (1933) 946]. Cherubism is an autosomal-dominant disorder in which the normal bone is replaced by cellular fibrous tissue and immature bone. Extracranial skeletal involvement is rarely seen in hereditary and non-hereditary forms of the disorder. The mandible is the most severely affected craniofacial component, in which uncontrolled growth of the malady deteriorates the aesthetic balance of the face. Bilateral swelling of the cheeks, mandibular enlargement and maxillary spongious hypertrophy cause orbital manifestations and tendency of eyes looking up to the sky. Thus, the pathognomic clinical feature resembles the appearance of "raised to heaven" Renaissance cherubs. The sporadic case concerns a child affected by cherubism. Radiographic and clinical data of the patient are presented and brief review of the literature is included.

title: Cherubism: a clinical, radiographic, and histopathologic comparison of 7 cases.
abstract: Cherubism is an uncommon fibro-osseous disorder of the jaws that presents with varying degrees of involvement and a tendency toward spontaneous remission. Lesions are characterized by replacement of bone with fibrovascular tissue containing abundant multinucleated giant cells. We attempted to study the relationships among the degree of cherubism, the radiographic extent of the jaw lesions, the histopathologic findings, and the clinical course of 7 patients.



In 7 patients diagnosed with cherubism, we evaluated the degree of fibrosis and perivascular cuffing, the presence of focal hemosiderin deposits, and giant multinucleated cell density (absent, few, moderate, or severe). Clinical course and progression were also assessed using a 4-point scale (improvement, no changes, modest progression, and marked progression).



The patients were followed up for an average of 8.5 years. Two patients exhibited clinical and radiographic improvement, while 3 showed no changes, and 2 progressed despite surgical treatment in 1 of them.



The course of cherubism in 1 of our patients may represent evidence of an association between the presence of abundant multinucleated giant cells, an increased extent of the lesions, and a more aggressive behavior of the disease.

title: Clinicopathologic study of 24 cases of cherubism.
abstract: The authors reviewed 24 cases of familial or nonfamilial cherubism. The age at onset was between 6 and 10 years. It was characterized by bilateral painless swelling of jaws and eyes-to-heaven appearance was visible when the maxillae were affected as well. Radiographs showed well-defined multilocular radiolucencies and with age, thick sclerotic borders were visible. A malocclusive and abnormal dentition, worse in the mandible can be seen. Histopathologically, numerous randomly distributed multinucleated giant cells and vascular spaces within a fibrous connective tissue stroma with or without eosinophilic collagen perivascular cuffing were apparent. Multinucleated giant cells were positive for osteoclastic specific markers, tartrate-resistant acid phosphatase and human alphaV beta3 integrin, 23C6. Results after follow-up were available for 14 cases. Of these, no treatment was carried out in five cases, cherubism resolved (three cases) or grew slowly (two cases); curettage or surgical contouring was performed in seven cases, during the rapid growth of the lesions. This not only gave good immediate results, but also arrested active growth of remnant cherubic lesions and even stimulated bone regeneration. Segmental mandibulectomy followed by reconstruction was performed in two cases with extensive lesion and the risk of pathologic fracture of the mandible, and excellent results were obtained.

title: Cherubism - new hypotheses on pathogenesis and therapeutic consequences.
abstract: The hereditary occurrence of cherubism indicates a probable genetic aetiology: a correlation with a mutation in the gene SH3BP2 has been demonstrated. A convincing concept of formal pathogenesis is not yet available. The study was aimed at advancing the understanding of the pathogenesis of cherubism by presenting a case study including genetic findings and an evaluation of the literature.



Because of its association with the development of the second and third molars, cherubism could be defined as a genetically determined alteration of tooth development. In this context, disturbed PTHrP - PTHrP receptor interaction induced by the mutation in SH3BP2 is discussed. The temporal and spatial determination of the clinical symptoms is explained by an interaction of SH3BP2-dependent signal transduction pathways with jaw morphogenesis (e.g. Hox-gene Msx-1). Because of the disease-induced lack of determination of the cap phase of the second and third molar, a spatial compartmentation, which is necessary for normal dental development, does not take place. This leads to dysregulation of mesenchymal bone building tissue areas, and to the development of giant cell granulomas with high osteoclastic activity. Because of the genetic determination of cherubism and the associated dedifferentiation of the diseased tissue, a surgical removal should be exclusively restricted to specific indications. Therefore an attitude of wait and see is preferred.

title: The aggressive form of cherubism: report of two cases in unrelated families.
abstract: Cherubism is a benign lesion that causes painless symmetrical enlargement of the jaws, usually with a familial tendency. We describe in two Chinese families two cases of the aggressive form of cherubism with extensive swelling on both sides of the mandible, typical microscopic findings, and apparent familial history.

title: Diagnostic Potential of 3D-Data–Based Reconstruction Software: An Analysis of the Rare Disease Pattern of Cherubism
abstract: Cherubism is an autosomal-dominant syndrome characterized by bilateral maxillomandibular bony degeneration, fibrous connective tissue hyperplasia, and displacement of permanent tooth germs. Reossification of the cystic lumen occurs spontaneously, but dislocated teeth must be realigned orthodontically. Advancements in virtual 3D reconstruction of anatomic structures based on computed tomography (CT) or cone beam CT data have provided for more predictable individual treatment planning. We evaluated two software programs for making densitometry and volume measurements of cystic areas in the mandibles, and for 3D visualization of permanent tooth germs within the cystic lumen, in two siblings with cherubism.

title: Two-Stage Surgical Treatment of Severe Cherubism
abstract: Cherubism is an autosomal-dominant syndrome characterized by excessive bilateral maxillomandibular bony degeneration followed by fibrous tissue hyperplasia. Eight patients (age, 6–15 years; mean, 11 years) with severe cherubism were treated with a 2-stage operation by the same senior surgeon (C.M.R.-A.) over an 18-year period, 1987 through 2005. Severity was based on a modified Motamedi classification system. The diagnosis was established clinically, radiographically, and histologically. Postoperative follow up ranged from 2 to 18 years (mean, 5.1 years). All patients underwent 2-stage surgical treatment. In the first stage, the anterior wall of the maxilla was osteotomized and removed (n = 5). The cherubic lesion was curetted from the maxilla and orbits. The maxilla was recontoured on the back table and then fixed orthotopically with wires. Alternatively, cortical bone windows were created, the maxillary and orbital lesions were curetted, and the maxilla was infractured and recontoured in situ with manual pressure (n = 3). Six months after the maxillary/orbital procedure, all patients underwent second-stage curettage and recontouring of the mandible using bony access windows and manual infracture. Satisfactory esthetic results were achieved in all patients. The patients remained clinically and radiographically disease-free throughout the follow-up period. The most profoundly affected patient sustained bilateral lower eyelid ectropion that resolved with full-thickness skin grafting. Although cherubism tends to abate by the fourth decade of life, early 2-stage surgical curettage provides a simple and reliable treatment that not only delivers immediate results, but also seems to arrest the growth of any remaining cherubic tissue.

title: A prosthetic treatment approach for a cherubism patient: A clinical report.
abstract: Cherubism is an early childhood disease that primarily involves the mandible and consists of painless mandibular enlargement with or without maxillary involvement and progresses rapidly over the course of several years. This clinical report describes the fabrication of maxillary fixed partial dentures and a mandibular overdenture for a 21-year-old man with cherubism.