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At least 19 recordsLinked to original sources
PubMed1998

Study of the cell biology and biochemistry of cherubism.

AIMS: 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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Bone Resorption↗
PubMed2003

A missense mutation in the SH3BP2 gene on chromosome 4p16.3 found in a case of nonfamilial cherubism.

OBJECTIVE: Cherubism is a rare hereditary multilocular cystic disease of the jaws, characterized by its typical appearance. Although nonfamilial cases have been reported, it is difficult to distinguish nonfamilial cherubism from central giant cell granuloma. Recent studies have revealed the point mutations in the SH3BP2 gene on chromosome 4p16.3 in cherubism families. In this article, the SH3BP2 gene in nonfamilial cherubism was examined. PATIENT: A 21-year-old Japanese woman with nonfamilial cherubism. INTERVENTIONS: Genomic DNA was purified from a blood sample obtained from the patient and used for direct sequencing. In addition, a sample of the lesion, resected during surgery, was used for histologic and immunohistochemical purposes. RESULTS: Genomic DNA sequencing found a Pro418Arg mutation in the SH3BP2 gene of the patient. In a histochemical analysis, the multinucleated giant cells proved to be strongly positive for PGM-1, KP-1, and tartrate-resistant acid phosphatase and faintly positive for osteopontin. CONCLUSIONS: The missense mutation Pro418Arg was identified in the SH3BP2 gene from a nonfamilial case of cherubism. DNA diagnosis may play a significant role in the identification of cherubism.

Acid Phosphatase↗
PubMed2000

Cherubism: a 36-year long-term follow-up of 2 generations in different families and review of the literature.

OBJECTIVE: To clarify the relationships between the varying clinical or radiographic features of cherubism. STUDY DESIGN: Nonparametric statistics were used in a long-term follow-up of 18 patients through 2 generations from 6 Danish families. RESULTS: The radiographic grade of cherubism was significantly related to sex, maximal buccal bone expansion, course of cherubism, and number of aplasia or ectopic impacted teeth, but it was not related to families. Normal dentition in nonaffected regions was present or was obtained in 14 of 14 patients (age, >14 years). Surgical treatment did not provoke growth of lesional tissue in 22 of 22 cases. Radiographically, the bone structure in the lesional areas was related to age in all grades of cherubism: new bone formation in radiolucent areas (age, >20 years), normal bone structure with multilocular sketches (age, 32 to 39 years), and completely normal bone structure (age, >41 years), also found in 7 of 7 carriers of cherubism (age, >32 years). CONCLUSIONS: This group analysis verifies the knowledge of cherubism previously based on cumulative reviews of findings in single-family and case reports.

Adolescent↗
PubMed2001

Orbital involvement in cherubism.

PURPOSE: To demonstrate the clinical, radiologic, and histopathologic features of a patient with orbital involvement in cherubism that prompted surgical treatment. DESIGN: Single interventional case report. INTERVENTION: Findings of the ophthalmic evaluation, computed tomography (CT) scans, intraoperative examination, and light microscopy of the specimens were analyzed. MAIN OUTCOME MEASURES: Globe displacement, orbital bony lesions detected on CT scans, histopathology, and postoperative results were assessed. RESULTS: A 27-year-old female was seen with a slowly progressive superonasal globe displacement and a temporal orbital mass bilaterally of 6 years' duration. She had a history of cherubism, but her cheeks and jaws had a normal appearance instead of the bilateral fullness of the lower half of the face typical of the disease. CT scans demonstrated multicystic bony lesions arising from the orbital floors bilaterally. The masses were excised using an anterior transcutaneous transseptal orbitotomy. Histopathology demonstrated numerous giant cells in a fibrovascular stroma, confirming the clinical diagnosis of cherubism. Postoperative recovery was complete. CONCLUSIONS: Orbital involvement in cherubism may develop beyond puberty, after stabilization or regression of the lesions in the jaws. Patients with cherubism should be routinely evaluated by an ophthalmologist.

Adult↗
PubMed2003

Novel mutation in the gene encoding c-Abl-binding protein SH3BP2 causes cherubism.

Cherubism is a rare autosomal dominant inherited condition caused by mutations in the c-Abl-binding protein SH3BP2. It is characterized by multiple cystic giant cell lesions of the jaw appearing in early childhood with stabilization and remission after puberty. In the present study, we used direct sequence analysis of the SH3BP2 gene of several individuals from a family with cherubism to search for additional SH3BP2 mutations resulting in cherubism. In affected relatives, we found a previously unreported G to A transition in exon 9 leading to a Gly to Arg substitution at amino acid position 420. G420R has been reported previously with a G to C transversion. To date there have been no disease causing mutations outside exon 9. Therefore, the amino acid sequence from positions 415 to 420 may represent a specific protein domain which, when disrupted, leads to the cherubism phenotype.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Neurofibromatosis presenting with a cherubism phenotype.

We report on a child who presented clinical manifestations of both neurofibromatosis type 1 (NF1) and cherubism. With genetic testing, we found a mutation in the NF-1 gene, confirming the neurocutaneous disorder. Histology when correlated with radiological evaluation of a mandibular biopsy was consistent with cherubism. This is the first report in the literature of a child with proven neurofibromatosis type 1 and cherubism without extragnathic lesions. This emphasises that cherubism is a clinical phenotype that can be associated with a number of germline mutations involving SH3BP2, PTPN11 and NF1.

Adolescent↗
PubMed2003

[Clinical and molecular genetic observations on families with cherubism over three generations].

BACKGROUND: Cherubism is a rare fibro-osseous disorder that almost exclusively affects the maxilla and mandible. CASE REPORT: We report on three affected males in three generations in family A, and ten affected patients in family B. The youngest affected relative in family A also had craniosynostosis. His father and grandfather had cherubism and clubbed fingers. RESULTS AND DISCUSSION: Cherubism was mapped to region 4p16.3. Because of the associated craniosynostosis, we excluded the FGFR3 gene as a candidate gene for cherubism. The inheritance pattern is autosomal dominant with variable expression. The penetrance is 100% in males and 50-70% in females. We found incomplete penetrance in males, which does not conform with all publications.

Adolescent↗
PubMed2005

Cherubism - new hypotheses on pathogenesis and therapeutic consequences.

AIMS: 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. RESULTS AND CONCLUSION: 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.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Cherubism: a clinical, radiographic, and histopathologic comparison of 7 cases.

PURPOSE: 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. PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Adolescent↗
PubMed2006

[Genetic aspects of cherubism].

INTRODUCTION: Cherubism is an extensive kystic process of the mandibula. The diagnosis is often established in children presented swelling of the jaws. The familial determinism of cherubism is well-known, and recently autosomal dominant cases have been described with detection of the exon 9 - SH3BP2 mutation. OBSERVATION: We describe the case of a 14-year-old boy with grade I cherubism diagnosed late. The familial genomic analyze conducted in Berlin was negative for the recently identified candidate gene. DISCUSSION: Apart from dominant cases cherubism sometimes occurs sporadically, some of the cases resulting from a neomutation of the candidate gene. The present case with familial bone homeostasis and dental disorders is an argument for the recessive transmission hypothesis or for another candidate gene.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Clinical and radiological evaluation of cherubism: a sporadic case report and review of the literature.

Many cases have been published on cherubism since Jones described it first time in three children of the same family [Am. J. Cancer 17 (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.

Cherubism↗
PubMed1996

Cherubism: diagnostic imaging and review of the literature in Japan.

Cherubism is a nonneoplastic disease of bone characterized by clinical, 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 family, often in multiple generations. On radiography the lesions have the appearance of bilateral multilocular radiolucent areas. On histopathologic evaluation the lesions show proliferating fibrous connective tissue containing numerous multinucleated giant cells. Since it was first described by Jones in 1933, many cases have been documented without restriction to any one country or ethnic group, but only a few cases have been reported in Japan, apparently because it is rare here. We report a case of cherubism in a 15-year-old boy and review the Japanese literature.

Adolescent↗
PubMed2001

Orbital involvement in cherubism.

Cherubism is a rare, inherited condition characterized by fibro-osseous lesions of the maxilla and mandible. It has recently been localized to chromosome 4p16.3. The fullness of the lower half of the face and retraction of the lower lids gives the characteristic 'eyes raised to heaven' cherubic appearance. A case report of a 7-year-old girl with extensive orbital involvement of cherubism is presented. The patient underwent multidisciplinary surgery for the bony lesions, which extended from the maxillary antrum into adjacent structures, including extensive extraperiosteal orbital involvement. Cherubism may have orbital manifestations including lower lid retraction, proptosis, diplopia, globe displacement and visual loss due to optic atrophy. Ophthalmologists should be aware of the syndrome, its ophthalmic features and overall management.

Cherubism↗
PubMed2001

Cherubism and its charlatans.

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.

Calcitonin↗
PubMed2004

Point mutations of 3BP2 identified in human-inherited disease cherubism result in the loss of function.

Adaptor protein 3BP2 positively regulates the high affinity IgE receptor (FcepsilonRI)-mediated activation of degranulation in mast cells. Genetic study identified the point mutations of 3BP2 gene in human-inherited disease cherubism. The multiple cysts in cherubism lesion of jaw bones are filled with the activated osteoclasts and stromal cells, including mast cells. By over-expression study using rat basophilic leukaemia RBL-2H3 mast cells, we have analysed the effect of the point mutations on the function of 3BP2 protein, which plays a positive regulatory role on FcepsilonRI-mediated mast cell activation. Over-expression of 3BP2 mutants suppressed the antigen-induced degranulation and cytokine gene transcription. Antigen-induced phosphorylation of Vav1, activation of Rac1, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen activated protein kinase (MAPK), inhibitor of nuclear factor kappaB kinase (IKK) and nuclear factor of activated T cells (NFAT) were all impaired in the cells over-expressing the cherubism mutants of 3BP2. Furthermore, cherubism mutations of 3BP2 may abrogate the binding ability to interact with chaperone protein 14-3-3. These results demonstrate that over-expression of the mutant form of 3BP2 inhibits the antigen-induced mast cell activation. It suggests that point mutations of 3BP2 gene cause the dysfunction of 3BP2 in vivo.

Adaptor Proteins, Signal Transducing↗
PubMed2000

[Man with cherubism].

Cherubism was diagnosed in a male when he was 6 years old. Cherubism is a benign, bilateral, painless lesion. It is commonly located in the mandible but in a minority of patients also in the maxilla. Cherubism is a familial condition with an autosomal dominant pattern of inheritance. At least one member of the family of the patient described had cherubism. The disease becomes manifest during early childhood and progresses until puberty when it spontaneously regresses. In the majority of patients no treatment is required. However, in the patient presented surgical procedures and odontological corrections were necessary. Due to a flare-up of the disease at the age of 22 years, the patient was treated with calcitonin for 1 year followed by bisphosphonates. During these treatments the disease symptoms diminished.

Adult↗
PubMed2000

Craniosynostosis in cherubism.

Cherubism is a rare autosomal dominant fibro-osseous disorder that affects almost exclusively maxilla and mandible. Extracranial skeletal involvement is rare. We report on three affected males in three generations. The youngest affected relative was examined at age 4 months. He also had craniosynostosis. His affected father and grandfather had cherubism and clubbing of the fingers. Cherubism was mapped to region 4p16. Because of the associated cranio-synostosis, we excluded the FGFR3 gene as a candidate gene for cherubism.

Adult↗
PubMed2003

Cherubism in siblings: a case report.

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.

Adolescent↗