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Osteogenesis imperfecta is a group of genetic disorders that mainly affect the bones. The term "osteogenesis imperfecta" means imperfect bone formation. People with this condition have bones that are brittle and easily broken. Multiple fractures are common, and in severe cases, can occur even before birth.
This condition affects an estimated 6 to 7 per 100,000 people worldwide. About 20,000 to 50,000 Americans may have been affected.
Researchers have identified several types of osteogenesis imperfecta. The types are often distinguished by their signs and symptoms, although their characteristic features overlap. Increasingly, specific bony changes and genetic factors are also used to define the different types of this condition.
Type I osteogenesis imperfecta, the mildest form of the condition, is characterized by bone fractures during childhood and adolescence that often result from minor trauma. Fractures occur less frequently in adulthood. People with this form of the condition typically have a blue or grey tint to the part of the eye that is usually white (the sclera) and may develop hearing loss in adulthood. Affected individuals are usually of normal or near normal height.
Type II osteogenesis imperfecta is the most severe form of the disorder. Infants with type II have bones that appear bent or crumpled and may fracture before birth. The chest is narrow, with a very small rib cage and underdeveloped lungs. Affected infants have short, bowed arms and legs; dark blue sclerae; hips that turn outward; and unusually soft and thin skull (calvarial) bones. Most infants with type II are stillborn or die shortly after birth, usually from respiratory failure.
Type III osteogenesis imperfecta is characterized by very fragile bones that may begin to fracture before birth. In some cases, rib fractures can cause life-threatening problems with breathing. Bone abnormalities tend to worsen over time and often interfere with mobility. People with this form of the disorder have very short stature; their adult height may be less than 3 feet. Type III osteogenesis imperfecta is also associated with blue sclerae that lighten with age, hearing loss beginning in adolescence, and a disorder of tooth development called dentinogenesis imperfecta.
Type IV osteogenesis imperfecta is a moderate form of the disorder. About 25 percent of affected individuals are born with bone fractures; others may not have any broken bones until later in childhood or adulthood. Although the sclerae may have a bluish tint in infancy, adults with this form of the condition usually have white sclerae. Additional features of type IV osteogenesis imperfecta can include mild short stature, hearing loss, and dentinogenesis imperfecta.
Researchers have proposed several additional types of osteogenesis imperfecta, but in most cases the genetic causes of these types have not been determined.
Mutations in the COL1A1 and COL1A2 genes are responsible for about 90 percent of all cases of osteogenesis imperfecta. These genes provide instructions for making proteins that are used to assemble type I collagen, which is the most abundant protein in bone, skin, and other tissues that provide structure and strength to the body (connective tissues).
Most of the mutations that cause osteogenesis imperfecta type I occur in the COL1A1 gene. These mutations reduce the amount of type I collagen produced in the body, which causes bones to be brittle and fracture easily. The mutations responsible for osteogenesis imperfecta types II, III, and IV can occur in the COL1A1 or COL1A2 gene. These mutations typically alter the structure of type I collagen molecules. A defect in the structure of type I collagen weakens connective tissues, particularly bone, resulting in the characteristic features of osteogenesis imperfecta.
Mutations in the CRTAP gene are responsible for rare cases of osteogenesis imperfecta. This gene provides instructions for making a protein that is involved in processing collagen molecules. Mutations in this gene reduce the amount of CRTAP protein or prevent cells from producing any of this protein. As a result, collagen molecules cannot form as they should, weakening connective tissues and leading to the bone abnormalities found in osteogenesis imperfecta.
Most cases of osteogenesis imperfecta are inherited in an autosomal dominant pattern. The type II is usually caused by new (sporadic) mutations because affected individuals do not live long enough to have children.
There is not yet a cure for osteogenesis imperfecta. Treatment is directed toward preventing or controlling the symptoms, maximizing independent mobility, and developing optimal bone mass and muscle strength.
A surgical procedure called “rodding?is frequently considered for individuals with osteogenesis imperfecta. This treatment involves inserting metal rods through the length of the long bones to strengthen them and prevent and/or correct deformities.