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Background: Cherubism is most commonly caused by rare heterozygous gain-of-function (GOF) missense variants in SH3BP2, which appear to signal through phospholipase C gamma 2 (PLCG2) to cause excessive osteoclast activity leading to expansile lesions in facial bones in childhood. GOF variants in PLCG2 lead to autoinflammatory PLCG2-associated antibody deficiency and immune dysregulation (autoinflammatory PLAID, or PLAID-GOF), characterized by variably penetrant autoinflammatory, autoimmune, infectious, and atopic manifestations. Cherubism has not been reported in PLAID to date., Objective: We determined whether GOF PLCG2 variants may be associated with cherubism., Methods: Clinical, laboratory, and genomic data from 2 patients with cherubism and other clinical symptoms observed in patients with PLCG2 variants were reviewed. Primary B-cell receptor-induced calcium flux was assessed by flow cytometry., Results: Two patients with lesions consistent with cherubism but no SH3BP2 variants were found to have rare PLCG2 variants previously shown to be GOF in vitro, leading to increased primary B-cell receptor-induced calcium flux in one patient's B cells. Variable humoral defects, autoinflammatory rash, and other clinical and laboratory findings consistent with PLAID were observed as well., Conclusion: GOF PLCG2 variants likely represent a novel genetic driver of cherubism and should be assessed in SH3BP2-negative cases. Expansile bony lesions expand the phenotypic landscape of autoinflammatory PLAID, and bone imaging should be considered in PLAID patients., Competing Interests: Disclosure statement Supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (R24 AI 17745 to J.D.M.), and the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (Z01-AR041198 to M.J.O.). Disclosure of potential conflict of interest: J. D. Milner is on the scientific advisory board for Blueprint Medicine and receives grant funding from Pharming. W. K. Chung is the on the board of directors of Rallybio and Prime Medicine. S. B. Eisig is cofounder of Epibone. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Competing Interests: Disclosures None of the authors reported any disclosures.

Objective: The purpose of this study was to identify factors associated with the management of the cleft dental gap after alveolar bone grafting., Methods: This was a retrospective cohort study of patients with unilateral cleft lip and alveolus or palate who had successful alveolar bone grafting. Our primary study outcome was alveolar cleft management (orthodontic closure or space maintenance). Our secondary study outcome was the rate of fixed dental rehabilitation. Univariate comparisons were made with SAS 9.4., Results: The final study sample consisted of 54 patients. Most patients were treated with orthodontic closure (55.6%). Patients missing multiple teeth ( P < 0.01) were less likely to receive orthodontic closure. Orthodontic closure was not associated with differences in intermaxillary midline coincidence ( P = 0.22) or the need for LeFort advancement ( P = 0.15). Only 41.7% of patients who were managed with space maintenance obtained a fixed prosthesis. Hispanic ethnicity ( P < 0.01) and Medicaid insurance ( P < 0.01) were associated with lower rates of fixed dental rehabilitation., Conclusions: Orthodontic closure was the most common approach, and it did not result in significant maxillary midline distortion. Less than half of patients treated with space maintenance obtained fixed restorations. Socioeconomic barriers are likely preventing access to definitive dental rehabilitation in patients with unilateral cleft lip and alveolus or palate., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)