Identifying the missing genetic components and characterizing the phenotypic landscape of cleidocranial dysplasia

The National Institute of Dental and Craniofacial Research awarded The Johns Hopkins University $107,828 under the Oral Diseases and Disorders Research program (CFDA 93.121) on December 4, 2026.

The funding supports research to identify missing genetic components and characterize the phenotypic landscape of cleidocranial dysplasia (CCD), an autosomal dominant skeletal dysplasia that impairs mobility, eating, and communication and increases susceptibility to osteoporosis. Approximately 70 percent of CCD cases carry pathogenic variants in RUNX2, a master regulator for skeletal development, leaving roughly 30 percent of clinically diagnosed cases without identified genetic etiology. Recent work has identified pathogenic variants in CBFB in eight patients with CCD diagnosis. The research leverages collaboration with CCD SMILES, the largest nonprofit patient support group specific to CCD. The project team has recruited a cohort of 115 patients with CCD and unaffected family members, completed comprehensive physical and dental examinations, and collected DNA samples for high-throughput sequencing analysis.

Performance occurs in Maryland. The period of performance extends through June 21, 2028.

Abstract

Cleidocranial dysplasia (CCD, omim: 119600) is an autosomal dominant skeletal dysplasia characterized by deformity of the teeth and bones resulting in impairment of mobility, eating, communication, decreased quality of life and higher susceptibility to osteoporosis, and skeletal pain. However, the CCD phenotype is highly variable and not fully characterized. Heterozygous pathogenic variants in RUNX2, a master regulator for skeletal development, have been identified in approximately 70% of patients with CCD . This leaves approximately 30% of CCD cases that are clinically diagnosed, but do not present with a pathogenic variant in RUNX2. Recently, pathogenic variants in cbfb have been identified in 8 patients that had the clinical diagnosis of CCD. The proposed project aims to 1) comprehensively define the CCD phenotype and 2) identify the missing genetic etiology of CCD by leveraging a collaboration with CCD smiles, the largest nonprofit patient support group specific to people with CCD. To complete these aims we have recruited a cohort of 115 patients with CCD and their unaffected family members and completed a comprehensive physical examination, dental examination, and collected DNA samples for high-throughput sequencing analysis.