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Cherubism — MFDS Part 1 MCQ

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HardOral PathologyCherubismMFDS Part 1

A 7-year-old child presents with painless, symmetrical expansion of the mandible and maxilla. Imaging shows bilateral multilocular radiolucencies, and biopsy demonstrates fibrovascular tissue containing numerous multinucleated giant cells. Serum calcium, phosphate and parathyroid hormone concentrations are normal. The child's mother had similar jaw swelling during childhood that regressed after puberty. Which molecular finding is most likely?

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Correct answer: D — A heterozygous gain-of-function variant in SH3BP2

The findings are characteristic of classic autosomal dominant cherubism, which is most commonly associated with heterozygous gain-of-function variants in SH3BP2. It causes symmetrical, giant-cell-rich multilocular jaw lesions beginning in childhood, often stabilising and regressing after puberty. The affected mother supports dominant inheritance. PTCH1 variants cause Gorlin syndrome, characterised by multiple odontogenic keratocysts rather than symmetrical giant-cell lesions. APC variants cause familial adenomatous polyposis/Gardner syndrome, in which jaw osteomas may occur. CDC73 variants cause hyperparathyroidism-jaw tumour syndrome; its jaw lesions are ossifying fibromas and biochemical hyperparathyroidism is usually present. Postzygotic activating GNAS variants cause fibrous dysplasia. Rare autosomal recessive cherubism associated with OGFRL1 has been reported, but this pedigree and phenotype indicate classic SH3BP2-related disease.

Reference: Kittaka M et al. Loss-of-function OGFRL1 variants identified in autosomal recessive cherubism families. JBMR Plus. 2024;8(6):ziae050. https://pubmed.ncbi.nlm.nih.gov/33941395/