Osteogenesis Imperfecta Health Article

Definition

Osteogenesis imperfecta (OI) is a group of genetic diseases in which the bones are formed improperly, making them fragile and prone to breaking.

Description

Collagen is a fibrous protein material that serves as the structural foundation of skin, bone, cartilage, and ligaments. In osteogenesis imperfecta, the collagen produced is abnormal and disorganized, which results in a number of abnormalities throughout the body, the most notable being fragile, easily broken bones.

There are four forms of OI, types I through IV. Of these, type II is the most severe and is usually fatal within a short time after birth. Types I, III, and IV have some overlapping and some distinctive symptoms, with the hallmark symptom being fragile bones.

OI is usually inherited as an autosomal dominant condition. In autosomal dominant inheritance, a single abnormal gene on one of the autosomal chromosomes (one of the first 22 non-sex chromosomes) from either parent can cause the disease. Only one parent needs to be a carrier in order for the child to inherit the disease. The parent affected by OI will have one abnormal gene and one normal gene. A child who has one parent with the disease therefore has a 50 percent chance of also inheriting the disease.

If both parents have OI caused by an autosomal dominant gene change, there is a 75 percent chance that the child will inherit one or both OI genes. In other words, there is a 25 percent chance of inheriting a faulty gene from the mother and a normal gene from the father, a 25 percent chance of inheriting a normal gene from the mother and a faulty gene from the father, a 25 percent chance of inheriting faulty genes from both parents, and a 25 percent chance of inheriting normal genes from both parents. It is difficult to predict the severity of OI in a child who has inherited two copies of the faulty gene because of its rarity.

There is no family history of OI in about 25 percent of children born with the disease. This occurs as a result of a spontaneous mutation of the gene in either the sperm or egg. The cause of such mutations is not known. Called new dominant mutation, the affected child subsequently has a 50 percent of passing the abnormal gene to his or her children. The risk of normal parents having a second child with OI, or of normal siblings going on to have affected children, does not appear to be greater than that of the general population.

In studies of families into which infants with OI type II were born, most of the babies had a new dominant mutation in a collagen gene. In some of these families, however, more than one infant was born with OI. Previously, researchers had seen this recurrence as evidence of recessive inheritance of OI type II. Subsequently, however, researchers concluded that the rare recurrence of OI to a couple with a child with autosomal dominant OI is more likely due to gonadal mosaicism. Instead of mutation occurring in an individual sperm or egg, it occurs in a percentage of the cells that give rise to a parent's multiple sperm or eggs. This mutation, present in a percentage of his or her reproductive cells, can result in more than one affected child without affecting the parent with the disorder. An estimated 2 percent to 4 percent of families into which an infant with OI type II is born are at risk of having another affected child because of gonadal mosaicism.

Demographics

OI affects equal numbers of males and females. It occurs in about one of every 20,000 births.

Causes and symptoms

Evidence suggests that OI results from abnormalities in the collagen gene COL1A1 or COL1A2 and possibly abnormalities in other genes. In OI, the genetic abnormality causes one of two things to occur. It may direct cells to make an altered collagen protein and the presence of this altered collagen causes OI type II, III, or IV. Alternately, the dominant altered gene may fail to direct cells to make any collagen protein. Although some collagen is produced by instructions from the normal gene, an overall decrease in the total amount of collagen produced results in OI type I.