Osteogenesis imperfect defect in
harshmohan textbook of pathology 7th edition. *osteogenesis imperfecta is an autosomal dominant or recessive disorder of synthesizing type1 collagen that constitutes 90 to 95 % bone matrix Osteogenesis Imperfecta Osteogenesis imperfecta (OI), also known as "brittle bone disease," is actually a group of genetic disorders caused by defec- tive synthesis of type I collagen. Because type I collagen is a major component of extracellular matrix in other pas of the body, there are also numerous extraskeletal manifesta- tions (affecting skin, joints, teeth, and eyes, for example). The mutations underlying OI characteristically involve the coding sequences for a1 or a2 chains of type I collagen. Because collagen synthesis and extracellular expo require formation of a complete and intact triple helix, any primary defect in a collagen chain tends to disrupt the entire structure and results in its premature degradation (an example of a dominant negative mutation) (Chapter 6). As a consequence, most defects manifest as autosomal domi- nant disorders and may be associated with severe malformations. There is, however, a broad spectrum of severity, and mutations that result in qualitatively normal collagen but at only reduced levels generally have milder manifestations. The fundamental abnormality in all forms of OI is too little bone, resulting in extreme skeletal fragility. Four major sub- types are recognized. The type II variant is uniformly fatal in utero or immediately postpaum as a consequence of multiple fractures that occur before bih. By contrast, patients with type I OI have a normal lifespan, with only a modestly increased proclivity for fractures during child- hood (decreasing in frequency after pubey). The classic finding of blue sclerae in type I OI is attributable to decreased scleral collagen content; this deficit causes a relative trans- parency that allows the underlying choroid to be seen. Hearing loss can be related to conduction defects in the middle and inner ear bones, and small misshapen teeth are a result of dentin deficiency. Ref Robbins 9/e p767
Collagen type I
Elastin
Collagen type IV
basement membrane
General pathology