Novel CHD7 Variants Associated with an Expanded Orofacial and Dental Phenotype

To systematically investigate the comprehensive spectrum of dental features across a well-characterized cohort of individuals harboring pathogenic CHD7 variants, and to explore the spatial expression pattern of CHD7 in craniofacial tissues using an in situ hybridization model to support the biological relevance of the observed phenotypes.

We performed a multi-case analysis (n = 9 pediatric patients; 7 M, 2 F; 1-18 years) with confirmed pathogenic/likely pathogenic CHD7 variants recruited. Genetic analysis utilized whole genome or exome sequencing. In situ hybridization in embryonic mouse models mapped CHD7 expression in craniofacial and dental primordia.

All patients presented with systemic CHD7-related features. Dental anomalies were frequent and diverse: cleft lip/palate (n = 2), tooth agenesis (n = 2), microdontia (n = 1), and malocclusion (n = 6). Notably, novel findings included the identification of odontoma or unexplained radiopaque lesions in two distinct cases. Genetic analysis identified seven novel CHD7 variants (two de novo). Murine in situ hybridization confirmed CHD7 expression in mandibular and dental primordia, supporting its role in odontogenesis.

We suggest that CHD7-related disorders may be associated with a broader spectrum of dental anomalies, including potentially underrecognized features. Dental assessments, including oral and radiographic examinations, may serve as adjunctive indicators and support further clinical and genetic investigation.