About OI – OI Foundation

Since the 1970’s, a list of numbered types has been used to describe the different forms of OI. The original list featured 4 types. Today, as a result of recent research, 15 types of OI have been identified. Many people with OI do not fit clearly into one of the identified types and not all characteristics are seen in each person. A description of the more common OI types follows. Understanding the individual’s OI type provides a starting point for understanding the person’s unique health care needs. Because of all of the variable features of OI, care for each person needs to be individualized.

• Type I OI: people with Type I OI, the mildest and most common form, may have only a handful of fractures or as many as several dozen fractures in a lifetime. They may have few obvious signs of the disorder. In Type I, there usually is little to no bone deformity. Height is less affected than in other types of OI, and many people with Type I are often similar in height to other family members. Muscle weakness, joint laxity, and flat feet are common. Dislocations and sprains may occur as well as fractures. Life expectancy appears to be average.
• Type II OI: is the most severe form of OI. Infants are quite small and are usually born with multiple fractures, an unusually soft skull, and an unstable neck. Limbs may be disproportionately small and legs may fall into a frog-like position. The head may be large for the size of the body. Almost all infants with Type II OI die at or shortly after birth, often due to respiratory problems. In the newborn period, it can be difficult to distinguish between Type II and severe Type III OI. This means that some children diagnosed clinically as Type II at birth may actually have Type III OI and have a longer life expectancy.
• Type III OI: People with Type III OI are born with fractures. X-rays may reveal healed fractures that occurred before birth. Common signs include short stature, progressive long bone deformities, spinal curvature, and a barrel-shaped rib cage. People with Type III OI may have anywhere from several dozen to several hundred fractures in a lifetime. Surgical correction of long bone bowing and scoliosis is common. Life expectancy varies. Some people with Type III OI have severe, sometimes fatal, respiratory problems in infancy or childhood. Some children with Type III OI may require supplemental oxygen. Some individuals succumb to respiratory problems in adulthood due to progressive rib cage and spine deformities. Other people with Type III OI will have a near average life span.
• Type IV OI: Type IV OI is the moderate type of OI. The clinical picture can be similar to Type I OI or more like Type III OI. People with this form of OI may be somewhat shorter than others in their family, have frequent fractures that decrease after puberty, and have mild to moderate bone deformity. Life expectancy for people with Type IV OI appears to be average.
• Type V OI: Is moderate in severity and is similar to Type IV in appearance and symptoms. Identifying features include hypertrophic calluses that may form at fracture or surgical procedure sites and restricted forearm rotation due to calcification to the membrane between the radius and ulna.
• Type VI OI: Type VI OI is another moderate form and is similar to Type IV in appearance. This is an extremely rare form. It is distinguished by a characteristic mineralization defect that can be seen in biopsied bone.

For additional information on OI Types see the OIF Fact Sheets.

Genetics and Inheritance

Most people with OI (>90%) have a mutation in one of the two copies of the genes (COL1A1 or COL1A3) that carry instructions for making type 1 collagen- the protein “scaffolding of bone and other connective tissues. These mutations either reduce the amount of type I collagen made or alter the quality of the protein. The remaining individuals with OI have mutations in other genes and the inheritance pattern in those families may be either dominant or recessive.

Children inherit two copies of each gene- one from each parent. When OI is caused by a dominant mutation, only one copy of the OI gene mutation is necessary for the child to have OI. In the majority of cases, the gene is either inherited from a parent who has OI or results from a spontaneous new mutation occurring at the time of conception. In rare cases, dominant OI can occur when a parent is mosaic for an OI mutation. This means that an OI causing mutation is present in a percentage of one parent’s cells, but does not cause any symptoms in the parent. For a child to inherit OI in a recessive manner, the gene mutation must come from both parents. In this situation, the parents do not have OI, but both must carry the mutation in their genes.

A person who has dominant OI has a 50 percent chance of passing on the disorder to each of his or her children. An affected child will have the same mutation, and therefore the same OI, as the parent. However, the expression- the degree of severity, or number of fractures- may be different. Unaffected siblings of a child with dominant OI have no greater risk of having children with OI than anyone in the general population. Unaffected siblings of a child with recessive OI have a 67% chance of being a carrier for the recessive gene. Genetic testing is available for all siblings.

In the last decade, it has been recognized that some individuals do not have mutations in COL1A1 or COL1A2 yet still have OI. In many of these individuals, it has been found that they have two altered copies of a gene, many involved in collagen processing or bone cell maturation. In these families, each parent has one copy of the altered gene and one copy of the normal copy and the condition is referred to as having “recessive inheritance”. The parents are asymptomatic and both must transmit the altered copy of the gene to have an affected child, a situation that will occur in about 25% of the pregnancies. For complete discussion about the inheritance pattern of OI and recurrence risks, parents are urged to consult with a medical geneticist or genetic counselor.