ABSTRACT
Cherubism is caused by mutations in SH3BP2. Studies of cherubism mice showed that tumor necrosis factor α (TNF-α)-dependent autoinflammation is a major cause of the disorder but failed to explain why human cherubism lesions are restricted to jaws and regress after puberty. We demonstrate that the inflammation in cherubism mice is MYD88 dependent and is rescued in the absence of TLR2 and TLR4. However, germ-free cherubism mice also develop inflammation. Mutant macrophages are hyperresponsive to PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns) that activate Toll-like receptors (TLRs), resulting in TNF-α overproduction. Phosphorylation of SH3BP2 at Y183 is critical for the TNF-α production. Finally, SYK depletion in macrophages prevents the inflammation. These data suggest that the presence of a large amount of TLR ligands, presumably oral bacteria and DAMPs during jawbone remodeling, may cause the jaw-specific development of human cherubism lesions. Reduced levels of DAMPs after stabilization of jaw remodeling may contribute to the age-dependent regression.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Cherubism/etiology , Inflammation , Myeloid Differentiation Factor 88/metabolism , Signal Transduction , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism , Adaptor Proteins, Signal Transducing/deficiency , Adaptor Proteins, Signal Transducing/metabolism , Animals , Cells, Cultured , Disease Models, Animal , Intracellular Signaling Peptides and Proteins/deficiency , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Jaw/diagnostic imaging , Liver/pathology , Macrophages/cytology , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Myeloid Differentiation Factor 88/deficiency , Myeloid Differentiation Factor 88/genetics , NF-kappa B/metabolism , Protein-Tyrosine Kinases/deficiency , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , RNA, Messenger/metabolism , Radiography , Syk Kinase , Toll-Like Receptor 2/chemistry , Toll-Like Receptor 4/chemistry , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
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.
Subject(s)
Osteitis/therapy , Acquired Hyperostosis Syndrome/diagnosis , Acquired Hyperostosis Syndrome/etiology , Acquired Hyperostosis Syndrome/therapy , Anemia, Dyserythropoietic, Congenital/diagnosis , Anemia, Dyserythropoietic, Congenital/etiology , Anemia, Dyserythropoietic, Congenital/therapy , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cherubism/diagnosis , Cherubism/etiology , Cherubism/therapy , Child , Female , Hereditary Autoinflammatory Diseases/diagnosis , Hereditary Autoinflammatory Diseases/etiology , Hereditary Autoinflammatory Diseases/therapy , Humans , Immunologic Deficiency Syndromes , Interleukin 1 Receptor Antagonist Protein , Magnetic Resonance Imaging , Male , Osteitis/diagnosis , Osteitis/etiology , Osteomyelitis/diagnosis , Osteomyelitis/etiology , Osteomyelitis/therapyABSTRACT
O Querubismo é uma doença óssea rara, não neoplasica, de caráter hereditário, que acomete crianças com predileção pelo gênero masculino cujas características clínicas são aumento da mandíbula e maxila de maneira bilateral e indolor, que tende a progredir até a puberdade, quando acontece o processo de remissão espontânea. O tratamento para a doença depende do curso clínico, porém não existe nenhum protocolo definindo qual é o melhor tipo de tratamento para cada caso. Sendo assim, fica a critério do cirurgião-dentista avaliar o melhor procedimento para seu paciente
Subject(s)
Diagnosis, Differential , Fibrous Dysplasia of Bone , Cherubism/etiology , Bone Diseases , Bone and Bones/injuries , RadiographyABSTRACT
AIM: The purpose of this article is to describe a case of multiple giant cell lesions of the mandible that occurred in a 14-year-old girl with phenotypic characteristics associated with Noonan Syndrome (NS). BACKGROUND: NS is a dysmorphic disorder characterized by hypertelorism, short stature, congenital heart defects, short and webbed neck, skeletal anomalies, and bleeding diathesis. REPORT: A 14-year-old girl with a previous diagnosis of NS (sporadic case) presented with multiple radiolucent lesions in the body and ramus of her mandible. SUMMARY: In terms of clinical behavior and the described radiographic characteristics, giant cells lesions with Noonan-like phenotype can be considered a form of cherubism. Therefore, surgical intervention is not necessary, but radiographic follow-up and observation is very important during the control and gradual regression of the lesions.
Subject(s)
Cherubism/etiology , Giant Cells/pathology , Mandibular Diseases/etiology , Noonan Syndrome/complications , Adolescent , Cherubism/diagnostic imaging , Cherubism/pathology , Female , Humans , Mandibular Diseases/diagnostic imaging , Mandibular Diseases/pathology , Radiography , Remission, SpontaneousABSTRACT
A case of cherubism in 6-year-old boy is reported. He presented with bilateral symmetrical enlargement of the jaw in addition to medially dislocated premature teeth, narrow V-shaped palatal vault, and mild upward turning of the eyes. Radiographs showed multiloculated osteolysis in both the mandible and maxilla. Histology revealed a non-neoplastic fibrous lesion, rich in multinucleated giant cells, consistent with giant-cell reparative granuloma. Since the original description of cherubism, various histologic interpretations have been proposed, particularly that of fibrous dysplasia. However, it should be emphasized that cherubism is a disease histologically indistinguishable from giant-cell reparative granuloma.
Subject(s)
Cherubism/etiology , Granuloma, Giant Cell/complications , Mandible , Maxilla , Cherubism/diagnosis , Cherubism/surgery , Child , Diagnosis, Differential , Follow-Up Studies , Granuloma, Giant Cell/diagnosis , Granuloma, Giant Cell/surgery , Humans , Male , Mandible/diagnostic imaging , Mandible/pathology , Mandible/surgery , Maxilla/diagnostic imaging , Maxilla/pathology , Maxilla/surgery , Radiography, Panoramic , Tomography, X-Ray ComputedABSTRACT
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.
Subject(s)
Humans , Male , Female , Bone Diseases, Metabolic/genetics , Cherubism/diagnosis , Cherubism/etiology , Cherubism/pathology , Cherubism/therapy , Chromosome Aberrations/diagnosis , Diagnosis, Differential , Genetic Diseases, Inborn/diagnosis , Jaw Abnormalities , Jaw Abnormalities/diagnosis , Jaw Abnormalities/surgery , Mandible/anatomy & histology , Mandible/surgery , Osteotomy , PrognosisABSTRACT
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)
Subject(s)
Humans , Male , Female , Cherubism/diagnosis , Cherubism/etiology , Cherubism/pathology , Bone Diseases, Metabolic/genetics , Genetic Diseases, Inborn/diagnosis , Cherubism/therapy , Chromosome Aberrations/diagnosis , Diagnosis, Differential , Prognosis , Osteotomy/methods , Jaw Abnormalities/diagnosis , Jaw Abnormalities/diagnostic imaging , Jaw Abnormalities/surgery , Mandible/surgery , Mandible/anatomy & histologyABSTRACT
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
Subject(s)
Humans , Female , Child , Cherubism/etiology , Cherubism/surgery , Cherubism/therapy , Mandible/pathology , Maxilla/pathologySubject(s)
Fibrous Dysplasia of Bone/classification , Fibrous Dysplasia of Bone/etiology , Osteomyelitis/classification , Osteomyelitis/etiology , Cementoma/classification , Cementoma/etiology , Cherubism/etiology , Bone Cysts, Aneurysmal/etiology , Granuloma, Giant Cell/classification , Granuloma, Giant Cell/etiology , Osteitis Deformans/etiologyABSTRACT
In the introduction to this paper an outline is given of dysostotic malformations of the jaw. Following this, the author reports observations made on sixty-five patients. Clinical, roentgenological, electromyographic, histological, and karyological, examinations made on this patient stock yielded numerous, hitherto undescribed results which, among other things, allow the previous classification of syndromes of the bronchial arch to be extended to include additional conditions.
