Exploring a cherubism bone phenotype outside the craniofacial region

Cherubism is a rare paediatric bone disease caused by gain-of-function mutations in the SH3BP2 gene. This condition is characterized by osteolysis of the jaw bone, which can be sometimes massive, whereby bone is replaced by fibrous tissue containing osteoclast-like multinucleated giant cells. Recently, a patient with a severe cherubism was reported to have, in addition to the craniofacial cherubism features, a low bone mass phenotype. To determine whether this patient was the exception or the rule, the cherubism phenotype was explored in ten more patients outside the cranio-facial. For the first time, inflammatory and bone blood markers together with bone density and growth in height and weight were systematically assessed in relation to the radiological and NFATc1 location classifications. We observed normal weight and height in the patients, as well as a significant increase in the bone metabolism blood markers (especially CTx and P1NP), which was associated with the severity of the cherubism. Our analysis also highlights the need for more systematic assessments of cherubism patients to improve our understanding of the cherubism natural history.