A newborn infant is being evaluated by the pediatrician in the hospital. On physical exam, the infant is noted to have blue sclerae and deformities in the legs (Figure 225-1). X-rays of the long bones of the legs reveal multiple fractures (Figure 225-2). Prenatal ultrasound screening in the second trimester showed bowing of long bones, fractures, and shortened limbs, suspicious for osteogenesis imperfecta (OI). The infant is treated with supportive care and a referral to genetics and orthopedics is made. The diagnosis of OI is formally established by identifying mutations in type 1 collagen.
Blue sclerae and leg deformities in a 3-day-old infant with osteogenesis imperfecta. The diagnosis was suspected before birth based on bony abnormalities seen during prenatal ultrasound imaging. (Used with permission from Betsy Tapani.)
Multiple fractures present at birth in a newborn with osteogenesis imperfecta. (Used with permission from Cleveland Clinic Children’s Hospital Photo Files.)
Osteogenesis imperfecta (OI) is a genetic disorder characterized by fragility of the skeletal system, and resulting in frequent fractures. The four major types of OI are caused by structural or quantitative defects in type 1 collagen, which is the primary component of the extracellular matrix of bone and skin protein.
Brittle bone disease (type 1 OI), Osteogenesis imperfecta congenita (type 3 OI).
Overall incidence of OI is 1 in 20,000 births. The number of individuals affected by OI in the US is estimated to be between 20,000 and 50,000.1
Eight types of OI have been described and are classified according to clinical presentation, radiographic findings, mode of inheritance, and molecular findings.
Types 1 through 4 of OI are the most common; types 5 to 8 are very rare.2
Type 1 is the most common form and is inherited in an autosomal dominant pattern. Type 4 is also inherited in an autosomal dominant pattern. Type 2 and Type 3 are usually the result of new mutations.
Type 2 is the most severe form; 50 percent of cases are stillborn.
The autosomal dominant forms of OI (types 1 and 4) occur equally in all racial and ethnic groups, and recessive forms (types 2 and 3) occur predominantly in ethnic groups with consanguineous marriages.
Etiology and Pathophysiology
OI types 1 through 4 are the result of mutations of genes that code for type I collagen, while types 5 to 8 are caused by mutations of other less-well characterized genes.
Types 1 and 4 are inherited in an autosomal dominant pattern and are caused by mutations in COL1A1 and COL1A2 genes that ...