Osteogenesis Imperfecta

Custom Search

Return to The Medical Biochemistry Page

Introduction to Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) represents a heterogeneous group of disorders, the vast majority of which are the result of mutations that affect the structure and function of type I collagens. Individuals with OI are characterized phenotypically with bone fragility. In addition, patients have soft tissue dysplasia, dentinogenesis imperfecta (abnormalities in the teeth), loss of hearing and alterations in the coloration of the sclera. Because of the heterogeneity of OI disorders this syndrome has been divided into four types.

Clinical Features of Osteogenesis Imperfecta

Type I OI is termed the mild type and is due to null mutations in the COL1A1 gene and results in bone fragility and blue sclera. The prevalence of type I OI is approximately 1 in 10,000 to 1 in 25,000. Diagnosis of type I OI is done by analysis of the production of type I procollagen in dermal fibroblasts in culture.

Type II OI is termed the perinatal lethal type and is due to mutations in the COL1A1 and COL1A2 genes. The mutations result in exon skipping and C-terminal proprotein mutants that interfere with collagen chain associations. Type II is characterized by severe bone fragility, absent calvarial mineralization and dark sclera. The frequency of type II OI is between 1 in 20,000 and 1 in 60,000. Affected infants are usually born premature and with low birth weight. Infants have characteristic facial features that include dark sclera, a beaked nose and an extremely soft calvarium. The outlook for type II OI patients is grim as this is a lethal disorder with life spans of only minutes to a few months. Death is usually the result of congestive heart failure, pulmonary insufficiency or infection.

Type III OI is referred to as the deforming type and is the result of exon skipping mutations in the COL1A1 and COL1A2 genes. The disorder is characterized by short stature, dentinogenesis imperfecta, light sclera and bone fragility leading to progressive deformities.

Type IV OI is called the mild deforming type and is the result of mutations in the COL1A1 and COL1A2 genes that result in exon skipping as well as the result of partial gene deletion mutants. The symptoms of type IV are similar to those of type III with individuals having mild short stature, dentinogenesis imperfecta and grayish sclera.

Last modified: February 1, 2012