What is osteogenesis imperfecta?

Osteogenesis imperfecta (OI) 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 break easily, often from mild trauma or with no apparent cause. Multiple fractures are common, and in severe cases, can occur even before birth. Milder cases may involve only a few fractures over a person's lifetime.

There are at least eight recognized forms of osteogenesis imperfecta, designated type I through type VIII. The types can be distinguished by their signs and symptoms, although their characteristic features overlap. Type I is the mildest form of osteogenesis imperfecta and type II is the most severe; other types of this condition have signs and symptoms that fall somewhere between these two extremes. Increasingly, genetic factors are used to define the different forms of osteogenesis imperfecta.

The milder forms of osteogenesis imperfecta, including type I, are characterized by bone fractures during childhood and adolescence that often result from minor trauma. Fractures occur less frequently in adulthood. People with mild forms 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.

Other types of osteogenesis imperfecta are more severe, causing frequent bone fractures that may begin before birth and result from little or no trauma. Additional features of these conditions can include blue sclerae, short stature, hearing loss, respiratory problems, and a disorder of tooth development called dentinogenesis imperfecta. The most severe forms of osteogenesis imperfecta, particularly type II, can include an abnormally small, fragile rib cage and underdeveloped lungs. Infants with these abnormalities have life-threatening problems with breathing and often die shortly after birth.

Osteogenesis imperfecta (OI) is a skeletal disease characterized by unusually fragile bones that break easily, often under loads that normal bones bear daily. This inherent weakness of the bones is due to a malfunction in the body’s production of the protein collagen. Collagen, of which there are at least 10 identifiable subtypes, is found in the connective tissues of the body and makes up a large portion of the bones and cartilage. It is the substance that holds the tissues together, providing strength and mass to the bones. For a person with OI, either the amount of collagen being produced is too little, or the quality being produced is poor. Either way, the bones of a person with OI are less dense and break easily. It is estimated that OI affects between 20,000 and 50,000 people in the United States.

OI is a genetic disease. The inheritance pattern is usually autosomal dominant. This means an affected person will have OI even though only one faulty gene has been passed along. This faulty gene can come from either parent, and it can affect either sex. Each child of an affected parent will have a 50 percent chance of developing OI.

Occasionally, a person will develop OI even though neither parent carried the faulty gene. This is called a spontaneous mutation. A person who develops OI will have the same chance of passing it on to a child as does someone who inherited the autosomal dominant gene.

There are four types of OI:

Type I: This is the most common and mildest form of OI. It is autosomal dominant in its inheritance, but it may also result from a spontaneous mutation. People with Type I OI average nearly 40 fractures before puberty; however, they experience only a few fractures after puberty. The collagen in Type I OI is normal, but the amount produced is less than normal. Some features of Type I OI include:

• Fragile bones
• Triangular-shaped face
• Blue sclerae (whites of the eye)
• Hearing loss beginning in their 20s
• Scoliosis (curvature of the spine)
• Thin, smooth skin
• Loose joints
• Low muscle tone
• Brittle teeth

Type II: Affecting approximately 10 percent of people with OI, Type II is the most severe form of this disease. The result of a spontaneous gene mutation, the collagen in Type II OI is improperly formed. The bones of people with Type II OI are extremely fragile and often have severe deformities. Type II OI frequently causes death at or shortly after birth.

Type III: Type III OI affects 20 percent of the people who have OI. Usually the result of a spontaneous mutation, it is common for a person with this type to have experienced 100 fractures by the time he or she reaches puberty. There are often fractures present at birth and X-rays may even show healed fractures that occurred before birth. The collagen in Type III OI is improperly formed. Some of the characteristics of Type III OI include:

• Short stature (some people only grow three feet tall)
• Sclera have a blue, purple, or gray tint
• Soft bones that not only break easily but also bend
• Loose joints
• Poor muscle development
• Barrel-shaped ribcage
• Triangular face
• Scoliosis
• Poor tooth development, often causing teeth to be brittle and discolored
• Possible hearing loss
• Possible respiratory problems

Type IV: The severity of this type of OI falls between Type I and Type III. It is inherited in an autosomal dominant manner, although it can also result from a spontaneous mutation. Fractures are most common in OI Type IV before puberty. The exception to this is in women, who after menopause experience a resurgence in the number of fractures. Typical characteristics of OI Type IV include:

• Below average height
• Scoliosis
• Mild to moderate bone deformity
• Triangular face
• Barrel-shaped ribcage
• Possible hearing loss
• Possible brittle teeth
• Loose, easily overstretched joints