Caffey disease: New perspectives on old questions

- Caffey disease is caused by an Arg to Cys substitution (R836C) in the α1(I) chain of type I collagen.
- The structural change caused by the R836C mutation may trigger collagen-dependent metabolic dysfunction of the matrix.
- Abnormal COX2/PGE signaling is likely to play a role in periosteal new bone formation in Caffey disease.
- Altered interplay between collagen matrix and bone formation in Caffey could provide novel insights into common disorders affecting bone metabolism.

The autosomal dominant form of Caffey disease is a largely self-limiting infantile bone disorder characterized by acute inflammation of soft tissues and localized thickening of the underlying bone cortex. It is caused by a recurrent arginine-to-cysteine substitution (R836C) in the α1(I) chain of type I collagen. However, the functional link between this mutation and the underlying pathogenetic mechanisms still remains elusive. Importantly, it remains to be established as to how a point-mutation in type I collagen leads to a cascade of inflammatory events and spatio-temporally limited hyperostotic bone lesions, and how structural and inflammatory components contribute to the different organ-specific manifestations in Caffey disease. In this review we attempt to shed light on these questions based on the current understanding of other mutations in type I collagen, their role in perturbing collagen biogenesis, and consequent effects on cell-cell and cell-matrix interactions.