Caffey disease: New perspectives on old questions

• Published in: Bone (New York, N.Y.) N.Y.), 2014-03, Vol.60, p.246-251
• Main Authors: Nistala, Harikiran, Mäkitie, Outi, Jüppner, Harald
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Biological and medical sciences; Caffey disease; Collagen; Collagen Type I - chemistry; Collagen Type I - genetics; COX-2; Extracellular matrix; Fundamental and applied biological sciences. Psychology; Humans; Hyperostosis, Cortical, Congenital - diagnostic imaging; Hyperostosis, Cortical, Congenital - pathology; Hyperostosis, Cortical, Congenital - physiopathology; Medicin och hälsovetenskap; Models, Biological; Molecular Sequence Data; Mutation - genetics; Orthopedics; PGE2; Radiography; TGFβ; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 8756-3282; 1873-2763; 1873-2763
• DOI: 10.1016/j.bone.2013.12.030

Abstract 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.