COL1A2 and Caffey disease: 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).