Cherubism - new hypotheses on pathogenesis and therapeutic consequences.
OBJECTIVE
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.


CONCLUSIONS
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.
Hyckel
Peter
P
Department for Maxillofacial Surgery/Plastic Surgery, Friedrich-Schiller University, Jena, Germany. peter.hyckel@med.uni-jena.de
Berndt
Alexander
A
Schleier
Peter
P
Clement
Joachim H
JH
Beensen
Volkmar
V
Peters
Hartmut
H
Kosmehl
Hartwig
H
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000367:Age Factors; D000465:Algorithms; D000848:Anodontia / Q000235:genetics; D002636:Cherubism / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D007571:Jaw Diseases / Q000235:genetics* / Q000473:pathology; D051957:MSX1 Transcription Factor; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000032:analysis
D048868:Adaptor Proteins, Signal Transducing; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C109073:SH3BP2 protein, human; D014157:Transcription Factors