The oral phenotype of CLS patients is characterized by hypodontia, microdontia, delayed eruption, and premature tooth loss.14–17 Employing Rsk2-deficient mice we have previously demonstrated that the premature tooth loss of CLS patients can be attributed to a cell-autonomous defect in cementoblast activity causing hypoplasia of root cementum, detachment of periodontal fibers, and subsequent alveolar bone loss.18 These findings were consistent with case reports describing that prematurely lost teeth of CLS patients had a reduced layer of root cementum.14,16. This evidence concerns the gene RPS6KA3 and Coffin-Lowry syndrome.