Cleidocranial dysplasia caused by a novel de novo RUNX2 splice-site variant

Cleidocranial dysplasia is an autosomal dominant disorder caused by RUNX2 variants. We report a Japanese boy with enlarged fontanelles in infancy, initially suspected of hypophosphatasia. Exome sequencing identified a novel de novo RUNX2 splice-site variant (c.685+2T>G), affecting the canonical donor site, and predicted to disrupt splicing. This novel variant expands the mutational spectrum of RUNX2 -associated cleidocranial dysplasia and highlights the value of early genetic diagnosis.