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Patient Story

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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.

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FIGURE 225-1

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.)

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FIGURE 225-2

Multiple fractures present at birth in a newborn with osteogenesis imperfecta. (Used with permission from Cleveland Clinic Children’s Hospital Photo Files.)

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Introduction

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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.

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Synonyms

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Brittle bone disease (type 1 OI), Osteogenesis imperfecta congenita (type 3 OI).

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Epidemiology

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  • 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.

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Etiology and Pathophysiology

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  • 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 ...

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