Cherubism - new hypotheses on pathogenesis and therapeutic consequences

Area of Science:

• Genetics
• Oral and Maxillofacial Surgery
• Developmental Biology

Background:

• Cherubism is a rare genetic disorder characterized by bilateral, symmetrical enlargement of the jaws.
• The hereditary nature suggests a genetic basis, with mutations in the SH3BP2 gene identified as a key factor.
• The precise pathogenesis and molecular mechanisms underlying cherubism remain incompletely understood.

Observation:

• This study presents a case of cherubism with detailed genetic findings.
• Literature review was conducted to evaluate existing knowledge on cherubism pathogenesis.
• The association between cherubism and the development of second and third molars was observed.

Findings:

• Cherubism is proposed as a genetically determined alteration in tooth development, linked to SH3BP2 gene mutations.
• A disturbed interaction between parathyroid hormone (PTHrP) and its receptor, induced by SH3BP2 mutation, is implicated.
• SH3BP2-dependent signaling pathways interacting with jaw morphogenesis (e.g., Hox-gene Msx-1) explain clinical symptom manifestation.

Implications:

• The findings suggest that cherubism results in dysregulation of mesenchymal bone tissue, leading to giant cell granulomas.
• The disease causes a lack of determination in the cap phase of second and third molar development, disrupting normal dental development.
• Given the genetic basis and tissue dedifferentiation, surgical intervention for cherubism should be limited to specific indications, favoring a conservative 'wait and see' approach.