Osteogenesis Imperfecta

Pathophysiology

Type I collagen is the most common form of collagen and is located in numerous regions, such as in bone, cartilage, tendons, ligaments, sclera of the eyes, and dermis of the skin. Osteoblasts, bone-forming cells, produce type I collagen extensively. Osteogenesis imperfecta is a disorder of osteoblast function and results in either a quantitative decrease in collagen in mild OI, or abnormal collagen in severe OI. Poor collagen quality yields brittle bone.

In the majority of cases, OI results from genetic mutations in the COLIA genes used to encode collagen. Most cases of OI are acquired by autosomal dominant inheritance in which each child of an affected parent has a 50 percent chance of developing OI. The remaining cases arise from spontaneous mutations. Osteogenesis imperfecta occurs worldwide in 1 out of 20,000 births and affects both sexes and all races equally. Fractures tend to occur early in life, but the age when symptoms begin varies widely.

Types and Clinical Features

Type I OI, the mildest and most common form, presents with an average of 40 fractures before puberty, blue sclerae or whites of the eyes, loose joints, muscle weakness, easy bruising and thin skin, scoliosis, brittle teeth, and a triangular face. Collagen quantity is [Page 1300]decreased, but structure is normal, so long as bone deformities are absent and patients have normal stature. Furthermore, 50 percent of patients also experience deafness by age 40.

Type II OI is the most severe form and is lethal shortly after birth. Newborns have bone deformities and fractures, and their underdeveloped lungs lead to respiratory failure. Collagen is abnormal in structure and insufficient in quantity.

In type III OI, collagen is sufficient but abnormal, leading to severe bone deformities. In addition to all of the type I symptoms, patients exhibit on average 100 fractures before puberty, short stature, barrel-shaped rib cages, chronic pain, hernias, and respiratory problems.

Type IV OI patients have an intermediate phenotype between types I and III in severity. Collagen, like in type III, is sufficient but abnormal. Patients have moderate bone deformities and short stature, but sclerae are normal in color.

Types V and VI are rare forms of OI that can be distinguished from type IV under the microscope. Several other disorders, such as Cole-Carpenter syndrome, Bruck syndrome, and idiopathic juvenile osteoporosis, resemble OI but do not have mutations in type I collagen genes.

Complications and Prognosis

Potential life-threatening complications include brain hemorrhage and basilar skull compression of the brainstem, which can cause severe neurological damage. During surgery, patients with OI are at higher risk of anesthesia complications. Patients also have recurrent respiratory infections and bone infections known as osteomyelitis. The prognosis varies based on the type of OI, but most children live productive lives despite the pain from fractures. Excluding the lethal type II form of OI, the life expectancy for patients is similar to that of healthy individuals.

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