Archive for the ‘Osteogenesis Imperfecta(OI)’ Category

Causes Osteogenesis Imperfecta

What Causes Osteogenesis Imperfecta?

The cause of osteogenesis imperfecta (OI) is a genetic defect that affects the body’s production of collagen. Collagen is the major protein of the body’s connective tissue and can be likened to the framework around which a building is constructed. In osteogenesis imperfecta, a person has either less collagen than normal, or a poorer quality of collagen than normal, and this leads to weak bones that fracture easily.

For people who have children with osteogenesis imperfecta, it is important to understand that nothing you or your spouse did during conception or pregnancy caused this condition in your child. Osteogenesis imperfecta has been prevalent for thousands of years.

Genetic counseling, which is available at most hospitals, may help you understand the type of osteogenesis imperfecta your child has. If you are thinking about having more children, you should consider contacting a geneticist, who can help determine the probability of recurrence of OI in your family.

What Causes Osteogenesis Imperfecta?

OI is caused by one of several genes that aren’t working properly. Genes carry our hereditary (family) information. We each have two copies of most genes: one set from each parent. Genes are what make you look like your biological family.

Each of the genes that cause OI plays a role in how the body makes collagen. Collagen is a material in bones that helps make them strong. When these genes aren’t working properly, there isn’t enough collagen, or the collagen doesn’t work properly. This leads to weak bones that break easily.

Most children inherit the gene that doesn’t work properly from one parent. Some inherit it from both parents. In some cases, neither parent passes on this gene. Instead, the gene stops working properly soon after the child is conceived.

What is Osteogenesis imperfecta?

Osteogenesis imperfecta (OI) is a genetic disorder that causes a person’s bones to break easily, often from little or no apparent trauma. OI is also called “brittle bone disease.” OI varies in severity from person to person, ranging from a mild type to a severe type that causes death before or shortly after birth. In addition to having fractures, people with OI also have teeth problems (dentinogenesis imperfecta), and hearing loss when they are adults. People who have OI may also have muscle weakness, loose joints (joint laxity) and skeletal malformations.

OI occurs in approximately 1 in 20,000 individuals, including people diagnosed after birth. OI occurs with equal frequency among males and females and among racial and ethnic groups. Life expectancy varies depending on how severe the OI is, ranging from very brief (lethal form, OI type II) to average.

There are four well-known types of OI. These types are distinguished mostly by fracture frequency and severity and by characteristic features. Three additional types of OI (type V, VI and VII) have also been identified.

The vast majority (90 percent) of OI is caused by a single dominant mutation in one of two type I collagen genes: COL1A1 or COL1A2.The COL1A1 and COL1A2 genes provide instructions for making proteins that are used to create a larger molecule called type I collagen. This type of collagen is the most common protein in bone, skin and other tissues that provide structure and strength to the body (connective tissues). OI type VII is caused by recessive mutations in the CRTAP gene.

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.

The Role of Genetics:

In most cases, the osteogenesis imperfecta cause is a dominant genetic defect (known as autosomal dominant) in the genes responsible for making collagen. Some children with osteogenesis imperfecta inherit the disorder from a parent. Other children are born with OI even though there is no family history of the disorder. In these children, the genetic defect occurred as a spontaneous mutation.

Because the defect that leads to osteogenesis imperfecta — whether inherited or due to a spontaneous mutation — is usually dominant, a person with OI has a 50 percent chance of passing on the disorder to each of his or her children.

Rarely, osteogenesis imperfecta can be inherited in an autosomal recessive pattern, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.

Genetic counselors can help people with osteogenesis imperfecta 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.

Causes:

As yet, medical science has been unable to pinpoint the exact cause of this debilitating condition. It is usually inherited as an autosomal dominant trait, but autosomal recessive and non-hereditary types of the disease are also known to occur. This disease is also closely related to a peculiar condition called dentinogenesis imperfecta. This is a condition that affects dentin formation in the tooth tissue. Dentin is the second layer present after enamel and protects the pulp, which is the nerve of the tooth.