It is well-known that genetic defects in the collagen type I genes COL1A1 and COL1A2 can cause osteogenesis imperfecta, Caffey disease and Ehlers–Danlos syndrome with a distinct bone or skin pathology, but our limited knowledge of the collagen folding hierarchy and its tissue-specific interfering factors makes it difficult to understand the mechanisms leading to such hyperostosis or fragility of bones, skin or blood vessels (81, –83). Here, COL1A1 is linked to Caffey disease.