[Unique Experience of Cherubism Targeted Therapy].

The family form of giant cell reparative granuloma or cherubism is a rare benign lesion of the jaws which causes face deformation reminiscent of the cherubs portrayed in Renaissance art. Radical surgery, especially in children before puberty, is impossible or irrational, because it leads to disablement. For four years, a child with cherubism was undergoing an outpatient supervision in the Department of Maxillofacial Surgery in Russian Children Clinical Hospital. During the observation period it was noted that tumor masses were slowly progressing leading to exoorbitism. The child had a diagnosis histological verification; a treatment using human monoclonal antibodies to RANKL was developed, adapted and approved by the ethical committee. The clinical effect was observed from the third month of therapy - jaws corners sharpened, the volume reduced. The control biopsy material taken at the end of the 6-month course did not reveal any giant cells which meant complete pathomorphism. Computed tomography showed that at the end of the therapy bone density increased by 6-7 times in the affected zones and was additionally growing over the next 6 months of observation. Such dynamics allowed making effective contouring surgery of excessive bone tissues. Inoperable and early stages of cherubism require a combined treatment which includes a course of monoclonal antibodies followed by alendronic acid therapy that increases osteoblasts survival. After the treatment, if it is necessary to improve the appearance, contouring surgery of excessive bone tissue is performed.

Craniofacial and Dental Features in Six Children With Cherubism.

Cherubism is an autosomal-dominant benign bone disorder, characterized by fibro-osseous lesions in the mandible and maxilla commonly caused by mutations in the SH3-binding protein 2-gene. The purpose of the authors' study was to analyze craniofacial and dental features of children diagnosed with cherubism, describe their treatment, and assess their dental age compared with norms for Finnish children. Six children were diagnosed, followed up and treated due to dental and skeletal disorders caused by cherubsim. The patients were followed up for an average of 91.5 months with emphasis on the skeletal changes and development of dentition. The treatment consisted of minor orthodontic treatment, dental extractions, and exposures. One patient underwent cosmetic mandibular surgery. All patients had lesions in the lower jaw and 5 of 6 patients had lesions in the maxilla as well. The patients were characterized by varying swelling of the jaws, premature loss of deciduous teeth in the affected area and widely spaced, displaced, un-erupted, or absent permanent teeth. The dental age was delayed at younger age but near to normal or even a little ahead at older age. Even though cherubism affects the jaws, jaw positions, and malocclusion, no common dentofacial proportions associated with the disease could be confirmed by cephalometric analysis. The surgical interventions did not provoke adverse reactions or local growth of the lesions.

Cherubism. A case report.

Cherubism is a rare disorder with autosomal dominant inheritance. It is classified as a benign fibro-osseous lesions and may involve either facial bone. Its typical dentofacial deformities are caused by mutations in the SH3BP2 gene. The protein encoded by SH3BP2 had a significant role in the regulation of osteoblasts and osteoclasts. Accordingly with the radiological findings, differential diagnoses includes fibrous dysplasia, giant cell granuloma, osteosarcoma, juvenile ossifying fibroma, fibrous osteoma, odontogenic cyst and hyperparathyroidism. The aim of the present report is twofold. First, we examine the importance of the proper management of these cases. Second, we describe this rare syndrome with the goal of proposing suitable treatments.

Clinicoradiologic features of cherubism: a case report and literature review.

Cherubism is a rare, hereditary, nonneoplastic bone disease. It is characterized by clinically evident bilateral, painless enlargements of the jaws that are said to give the patient a "chubby" appearance. This article presents a case of cherubism in a 5-year-old girl with painless bilateral swelling. Panoramic radiographs and a computed tomography scan showed bilateral multilocular radiolucent areas with cortical expansion. Histopathologic examination revealed proliferating fibrous connective tissue containing numerous multinucleated giant cells.

Orthodontic treatment in cherubism: an overview and a case report.

INTRODUCTION: Cherubism is a rare hereditary disease that frequently manifests as a painless enlargement of the mandible and/or maxilla. The disease usually progresses rapidly during the first and second decades of life but it is self-limiting and often regresses. Although few orthodontic case reports describing cherubic patients exist, the timing and extent of surgical intervention is controversial. AIM: This present paper aims to review the treatment literature and provide a case report of a patient who underwent orthodontic/surgical management. METHODS: The patient presented with severe cherubism in her late teenage years; her main complaint was poor facial and dental appearance. Multiple teeth were missing and those present demonstrated significant preoperative root resorption. Treatment consisted of orthodontic alignment of the upper anterior teeth and a recontouring osteotomy. RESULTS: Confirmed by the patient, the combination approach led to a significant improvement in facial aesthetics and better self-esteem. Tooth movement through the osseous lesions was uneventful and no further root resoption was observed. CONCLUSION: Orthodontic treatment may be undertaken in those affected by Cherubism even with pre-existing idiopathic root resorption, but patients need to be appropriately informed and consented.

Autoinflammatory bone diseases.

Autoinflammatory bone disease is a new branch of autoinflammatory diseases caused by seemingly unprovoked activation of the innate immune system leading to an osseous inflammatory process. The inflammatory bone lesions in these disorders are characterized by chronic inflammation that is typically culture negative with no demonstrable organism on histopathology. The most common autoinflammatory bone diseases in childhood include chronic nonbacterial osteomyelitis (CNO), synovitis, acne, pustulosis, hyperostosis, osteitis syndrome, Majeed syndrome, deficiency of interleukin-1 receptor antagonist, and cherubism. In this article, the authors focus on CNO and summarize the distinct genetic autoinflammatory bone syndromes.

The role of MRI and CT in diagnosis and treatment planning of cherubism: a 13-year follow-up case report.

AIM: Cherubism is characterised by mesenchymal alterations during the development of the jaws secondary to perivascular fibrosis. According to the ALARA (As Low As Reasonably Achievable) principle, it is important to avoid conditions where the amount of radiation used is more than that needed for the procedure, because there is no benefit from unnecessary radiation. However, the use of MRI has been poorly studied in cherubism. MATERIALS AND METHODS: The patient underwent head and neck MRI and 3D CT for imaging assessment. RESULTS: MRI is necessary to evaluate the extension of dysplastic tissue and the cystic part of the lesions. Bone window CT only allows evaluation of strong densitometric alterations of cherubism lesions. Moreover, on radiographic film it is not always possible to distinguish fibrous tissue from mucous pseudocystic tissue. By contrast, these differences are readily evident on MRI. CONCLUSION: MRI, in addition to other traditional radiographs and CT, could be useful in helping the clinician in the diagnosis and treatment of cherubism.

The surgical and orthodontic management of cherubism in a growing child.

Cherubism is a rare non-neoplastic disease that affects the jaws causing significant destruction and disfigurement. The disease also affects the normal eruption, occlusion and function of the dento-alveolar complex. Cherubism may radiographically and histologically resemble central giant cell granuloma, fibrous dysplasia and other giant cell lesions. The case of a 15-year 4-month-old girl with no obvious facial swelling or signs of cherubism is described in this report. The patient presented with a dental malocclusion that included the ectopic eruption and displacement of teeth caused by the lesion. The radiographic findings derived from Cone Beam Computed Tomography (CBCT) technology are described. This case report details the orthodontic and surgical diagnosis and management of a teenager during the post growth period.

Clinical care of children with sterile bone inflammation.

PURPOSE OF REVIEW: To review the current literature of sterile bone inflammation in childhood and to evaluate the evidence for clinical care including diagnostic methods and treatment. RECENT FINDINGS: Chronic noninfectious osteomyelitis includes several different entities marked by sterile bone inflammation associated with histologic evidence of a predominant neutrophil infiltration in the absence of autoantibodies and autoreactive T cells, some of which are associated with a genetic mutation. Whole body MRI is helpful in detecting asymptomatic lesions. Initial treatment with NSAIDs is usually sufficient to control symptoms as the bone heals. However, if the lesions persist and do not respond to first-line treatment, or involve the spine or hip, treatment with bisphosphonate will usually lead to a resolution of symptoms. Rarely, treatment with anti-TNF agents is required. SUMMARY: This review summarizes recent information on diagnosis, treatment and prognosis of disorders involving sterile bone inflammation in childhood. It also addresses the evolving differential diagnosis for autoinflammatory disorders that include sterile bone inflammation and presents a treatment algorithm for management.

Unexpected matrix diseases and novel therapeutic strategies.

Within the framework of a broad definition of the extracellular matrix (ECM), this review discusses three genetic disorders in which major pathogenetic features have been traced back to alterations in the levels/activities of matrix components. In each case, disease-associated alterations are found both intra- and extracellularly. The nature of the ECM involvement is surprising, offers an exciting therapeutic opportunity, and deepens our understanding of ECM-cell interactions. The first of these disorders, cherubism, is a case of inflammatory bone loss in the jaws of children for reasons that are surprisingly systemic in nature, considering the local nature of the disease. The primary defect involves an intracellular signaling molecule, but a major pathogenetic component and therapeutic target of the disease is the extracellular cytokine tumor necrosis factor alpha. The second disorder, Knobloch syndrome, is caused by recessive mutations in collagen XVIII. Although this protein has been classified as belonging to a group of structural macromolecules, the consequence of the mutations is impairment of cellular metabolism. The third disorder, infantile hemangioma, is a common tumor of capillary endothelial cells in infancy. The tumor appears within a few days/weeks after birth, grows rapidly over several months, and regresses over several years. The proliferative phase is the result of constitutively high levels of vascular endothelial cell growth factor (VEGF)-dependent signaling through VEGF receptor 2 (VEGFR2), but recent studies have led to the surprising conclusion that abnormalities in a cell-surface receptor complex controlling expression of the VEGF decoy receptor VEGFR1 is the underlying cause.

Familial cherubism: the experience of the Moscow Central Institute for Stomatology and Maxillo-Facial Surgery.

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.

Querubismo: relato de caso / Cherubism: case report

O querubismo é uma desordem óssea hereditária autossômica dominante que caracteriza-se pelo aumento indolor de volume da mandíbula e maxila em crianças. A lesão inicia na infância e desenvolve-se até a adolescência, quando paralisa seu curso e involui na idade adulta. O diagnóstico geralmente é realizado por meio de exames radiográficos, histológicos, evolução clínica da doença e hereditariedade. Relatamos um caso de um menino de 11 anos que apresentava história familiar positiva e aumento bilateral da face progressivamente desde os dois anos de idade. Foi realizado o diagnóstico de querubismo baseado nos achados clínicos, radiográficos e do histórico familiar. O tratamento proposto foi observação da evolução da lesão e acompanhamento clínico e radiográfico até que ocorra o processo autolimitante e involutivo das estruturas ósseas envolvidas.

Cherubism--clinical picture and treatment.

UNLABELLED: Cherubism is a rare, painless, disfigurating disease primarily affecting bones of the jaws. OBJECTIVE: 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. PATIENTS: 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. RESULTS: Good aesthetic and long lasting effect was reached in the operated patient. CONCLUSIONS: 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.

[Man with cherubism]. / Een man met cherubisme.

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.

Querubismo / Cherubism

El querubismo es una anomalía genética de carácter hereditario autosómico dominante que afecta el tejido óseo en forma uni o bimaxilar. Junto con la displasia fibrosa -de acuerdo con la clasificación de la IRCOT- se encuentra dentro de las lesiones óseas no neoplásicas. Las manifestaciones comienzan entre los 18 meses y los 4 años de edad. El tamaño de los maxilares aumenta hasta aproximadamente los 7 años. Durante los últimos años de la adolescencia, la enfermedad puede sufrir involución o ser activa hasta aproximadamente los 20 años, especialmente cuando se presenta en el maxilar inferior. Radiográficamente se observan zonas osteolíticas extensas. El cuadro histológico muestra un estroma fibroso, altamente vascular, con células gigantes multinucleadas y un pequeño manguito colágeno alrededor de los vasos sanguíneos. Según nuestra experiencia, el tratamiento a seguir será efectuar controles frecuentes clínico-radiográficos, reservando la cirugía para aquellos casos en los que los trastornos funcionales y estéticos deben ser resueltos antes de esperar la remisión espontánea.

Querubismo / Cherubism

El querubismo es una anomalía genética de carácter hereditario autosómico dominante que afecta el tejido óseo en forma uni o bimaxilar. Junto con la displasia fibrosa -de acuerdo con la clasificación de la IRCOT- se encuentra dentro de las lesiones óseas no neoplásicas. Las manifestaciones comienzan entre los 18 meses y los 4 años de edad. El tamaño de los maxilares aumenta hasta aproximadamente los 7 años. Durante los últimos años de la adolescencia, la enfermedad puede sufrir involución o ser activa hasta aproximadamente los 20 años, especialmente cuando se presenta en el maxilar inferior. Radiográficamente se observan zonas osteolíticas extensas. El cuadro histológico muestra un estroma fibroso, altamente vascular, con células gigantes multinucleadas y un pequeño manguito colágeno alrededor de los vasos sanguíneos. Según nuestra experiencia, el tratamiento a seguir será efectuar controles frecuentes clínico-radiográficos, reservando la cirugía para aquellos casos en los que los trastornos funcionales y estéticos deben ser resueltos antes de esperar la remisión espontánea. (AU)

Querubismo, reporte de un caso con seguimiento de veinte años / Cherubism, report of a twenty-year follow-up case

El término "querubismo" fue creado por W.A. Jones en 1933. Es una afección con deformación facial que no determina cambios sistémicos ni compromiso alguno de la salud general del paciente, siendo la química hemática completamente normal. Se presenta un caso clínico de un paciente con querubismo y su seguimiento desde los 2 y medio a los 22 años de edad. En el seguimiento clínico y radiográfico de la enfermedad se aprecia la evolución de la afección; primariamente con un crecimiento bilateral del rostro; a los 18 años se observó una estabilización clínica o regresión de la lesión y por último una importante secuela estética localizada en el tercio inferior de la cara. La secuela estétic afue corregida mediante un tratamiento quirúrgico-protético

Querubismo / Cherubism

Os autores apresentam um caso de Querubismo em uma criança do sexo feminino de 7 anos de idade, dando características clínicas e radiográficas e declinam sobre todo o acompanhamento do tratamento clínico e cirúrgico da paciente durante 7 anos, mostrando também a involução progressiva da doença

[A rare facial disorder: cherubism]. / Une affection rare de la face: le chérubisme.

A rare disorder involving primarily the maxillary region of the face, cherubism has a special place in the galaxy of osteolytic maxillary tumors. This disease is genetically transmitted and its pathogenesis is unknown at present. Its prognosis is considered as favorable since it progresses toward phases of regression and then disappearance--at least partial--of lesions. The main sequelae involve the teeth since agenesis often occurs which--as in the case presented here--is not very easy to correct.