What IS O.I.?

What is O.I.?

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Definition
Osteogenesis imperfecta (O.I.) is a genetic disorder characterized by bones that break easily, often from little or no apparent cause. A classification system of different types of O.I. is commonly used to help describe how severely a person with O.I. is affected. For example, a person may have just a few or as many as several hundred fractures in a lifetime.

Prevalence
While the number of people affected with O.I. in the United States is unknown, the best estimate suggests a minimum of 20,000 and possibly as many as 50,000.

Diagnosis
O.I. is caused by genetic defects that affect the body’s ability to make strong bones. In dominant (classical) O.I., a person has too little type I collagen or a poor quality of type I collagen due to a mutation in one of the type I collagen genes. Collagen is the major protein of the body’s connective tissue. It is part of the framework that bones are formed around. In recessive O.I., mutations in other genes interfere with collagen production. The result in all cases is fragile bones that break easily.

It is often, though not always, possible to diagnose O.I. based solely on clinical features. Clinical geneticists can also perform biochemical (collagen) or molecular (DNA) tests that can help confirm a diagnosis of O.I. in some situations. These tests generally require several weeks before results are known. Both the collagen biopsy test and DNA test are thought to detect almost 90% of all type I collagen mutations. 

A positive type I collagen study confirms the diagnosis of dominant O.I., but a negative result could mean that either a collagen type I mutation is present but was not detected or the patient has a form of the disorder that is not associated with type 1 collagen mutations or the patient has a recessive form of O.I. Therefore, a negative type I collagen study does not rule out O.I. When a type I collagen mutation is not found, other DNA tests to check for recessive forms are available.

Inheritance Factors
Most cases of O.I. (85-90%) are caused by a dominant genetic defect. This means that only one copy of the mutation carrying gene is necessary for the child to have O.I. Children who have the dominant form of O.I. have either inherited it from a parent or, when the parent does not have O.I., as a spontaneous mutation.

Approximately 10-15 percent of cases of O.I. are the result of a recessive mutation. In this situation, the parents do not have O.I., but both carry the mutation in their genes. To inherit recessive O.I. the child must receive a copy of the mutation from both parents.

When a child has recessive O.I., there is a 25 percent chance per pregnancy that the parents will have another child with O.I. Siblings of a person with a recessive form of OI have a 50 percent chance of being a carrier of the recessive gene. DNA testing is available to help parents and siblings determine if they are carriers of this type of gene mutation.

A person with a form of O.I. caused by a dominant mutation has a 50 percent chance of passing on the disorder to each of his or her children. If one parent has O.I. because of a recessive mutation, 100 percent of their children will be carriers of the recessive O.I. mutation. Whether any of these children will have O.I. will depend on their inheritance from the other parent. Genetic counselors can help people with O.I. and their family members further understand OI genetics and the possibility of recurrence, and assist in prenatal diagnosis for those who wish to exercise that option. For more information on O.I. inheritance, see the O.I. Foundation fact sheet titled “Genetics.”