• collagen type I;
  • cranial abnormalities;
  • osteogenesis imperfecta;
  • phenotype–genotype correlation;
  • Wormian bones


The presence of a larger than usual number of Wormian bones (accessory skull bones completely surrounded by a suture line) is a well-known radiographic sign of osteogenesis imperfecta (OI), but the phenotypic and genotypic correlates are not well characterized. In the present study we retrospectively analyzed skull radiographs of 195 OI patients (median age 11.8 years, range 0.4–48 years; 100 female). A significant number of Wormian bones (SNWB, defined as the presence of 10 or more Wormian bones) were found in at least one patient in all of the OI types studied (I, III to VII). SNWB were observed in 35% of patients with OI type I, in 96% of patients with OI type III and 78% of patients with OI type IV. SNWB were present in 28% of patients with haploinsufficiency (nonsense and frameshift) mutations in COL1A1, in 96% of patients with helical glycine substitutions in the alpha 1 chain of collagen type I and in 72% of patients with helical glycine substitutions in the alpha 2 chain of collagen type I. Stepwise multivariate logistic regression analysis showed that height z-score, an indicator of disease severity, was inversely related with the prevalence of SNWB. SNWB were visible in 19 of the 26 patients who had skull radiographs in the first year of life, including a 2-week-old newborn. Thus, it appears that SNWB occur more frequently in more severely affected OI patients and seem to develop mostly in utero. © 2010 Wiley-Liss, Inc.