Cherubism: a systematic literature review of clinical and molecular aspects

The purpose of this review was to integrate the clinical, radiological, microscopic, and molecular data of published cherubism cases, in addition to therapeutic approaches, to provide more concise information about the disease. An electronic search was undertaken in September 2019. Eligibility criteria included publications having enough clinical, radiological, and histological information to confirm the diagnosis. A total of 260 publications reporting 513 cherubism cases were included. Familial history was observed in 310/458 cases (67.7%). SH3BP2 mutations were reported in 101/108 cases (93.5%) and mainly occurred at protein residues 415, 418, 419, and 420. Retrospective clinical grading was possible in 175 cases. Advanced clinical grading was associated with tooth agenesis, but not with other clinical, radiological, and genetic features. Specific amino acid substitutions of SH3BP2 mutations were not associated with the clinical grading of the disease. 'Wait and see' was the most common therapeutic approach. In a small number of cases, drugs were used in the treatment, with variable response. In conclusion, there is no clear correlation between the genotype and the phenotype of the disease, but additional genomic and gene expression regulation information is necessary for a better understanding of cherubism.