Osteogenesis Imperfecta

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. It serves as the structural foundation of skin, bone, cartilage, and ligaments. In osteogenesis imperfecta, the collagen produced is faulty and disorganized. This results in a number of defects throughout the body, the most notable being fragile, easily broken bones.

OI affects equal numbers of males and females. It occurs in about one of every 30,000 births.

Causes & symptoms

Genes are the structures which pass biological information on from a parent to a child. The information contained in genes organizes the development of all the cells and tissues throughout the body. A person receives one set of genes from each parent. Because osteogenesis imperfecta is a genetic disorder, the gene which causes it can be passed on from an affected individual to his or her offspring. In dominant forms of OI, a person needs to have only one defective gene to actually develop the disorder. In recessive forms of OI, a person needs to have two defective genes, one from each parent, to develop the disorder. Sometimes OI cannot be traced back to a parent with the disorder. In these cases, the genetic defect is said to be a spontaneous mutation. This means that some unknown event has caused a gene (which functions normally in the parent) to develop a permanent defect. A person who has OI due to a spontaneous mutation can then pass on this defective gene to his or her future offspring.

There are four forms of OI, called Types I through IV. Of these, Type II tends to be the most severe, and is usually fatal within a short time of birth. Types I, III, and IV have some overlapping and some distinctive symptoms. These include:

• Weak bones which break (fracture) easily. In some forms of OI, these fractures occur even before birth. People with type I OI have about 20-40 fractures before puberty; people with OI Type III may have more than 100 fractures before puberty. Fractures often decrease in frequency after puberty, although women with OI have increasing numbers of fractures after menopause.
• Loose, unstable joints (due to abnormal structure of the ligaments), resulting in a high risk of dislocation.
• A bluish tinge to the white of the eye (the sclera).
• A curved and twisted spine (scoliosis).
• Hearing loss (due to malformation and fractures of the tiny bones in the middle ear which are necessary for hearing).
• Abnormally fragile, discolored (bluish-yellow) teeth.
• Often shorter-than-normal final height, depending on the type of OI. In OI Type I, height is slightly short or close to normal; in OI Type III, height is quite abnormal, with growth stopping around three feet; in OI Type IV, final height is somewhat shorter than normal.
• Thin, fragile skin.
• A high risk of complications such as hernias and heart valve abnormalities.

Other complications vary according to the type of OI. In OI Type I, the face is often somewhat abnormal in shape, appearing triangular. In OI Type II, the rib cage may be abnormally formed, restricting the lungs and resulting in breathing difficulties. The arms and legs are often shorter than normal, with bowing of the bones. People with OI Type IV have the most difficulty with dislocations of their overly lax joints.

Diagnosis

Diagnosis is usually suspected when a baby has bone fractures after having suffered no apparent injury. Sometimes the bluish sclera serves as a diagnostic clue. Unfortunately, because of the unusual nature of the fractures occurring in a baby who cannot yet move, some parents have been accused of child abuse before the actual diagnosis of osteogenesis imperfecta was reached.

The diagnosis is confirmed by taking a tiny sample of the patient's skin (a biopsy), and performing tests on this sample in a laboratory. The collagen fibers in the skin are studied for evidence of abnormalities. These tests are highly specialized, and the results may not be available for as long as six months. Furthermore, this type of testing will yield a falsely negative result in about 15% of all people who have obvious symptoms of OI. Currently, this is the only test available to diagnose OI; genetic testing is not yet available.

Treatment

There are no treatments available to cure OI, nor to prevent most of its complications. Most treatments are aimed at treating the fractures and bone deformities which OI causes. Splints, casts, and braces are all used. Rodding refers to a surgical procedure in which a metal rod is implanted within a bone (usually the long bones of the thigh and leg). This is done when bowing or repeated fractures of these bones has interfered with a child's ability to begin to walk.

Other treatments include hearing aids and early capping of teeth. Patients may require the use of a walker or wheelchair. Pain may be treated with a variety of medications. Swimming is a form of exercise which puts a minimal amount of strain on muscles, joints, and bones. It is helpful for increasing muscle and, therefore, joint strength.

Alternative treatment

Acupuncture, naturopathic therapies, hypnosis, relaxation training, visual imagery, and biofeedback have all been used to try to decrease the constant pain of fractures.

Prognosis

Fifty percent of all babies with OI Type II are born dead. The rest of these babies usually die within a very short time of being born. The prognosis for people with other types of OI is quite variable, depending on the severity of the disorder and the number and severity of the fractures and bony deformities.

Prevention

There is no known way to prevent OI, although adults with OI should be carefully counseled regarding the chance of their offspring being born with the disease. In the dominant form of OI, a child who has one parent with the disease has a 50% chance of also having the disease. In the recessive form of OI, a child who has two parents with the disease has a 25% chance of having the disease, a 25% chance of being completely unaffected, and a 50% chance of being a carrier. A carrier is someone who does not have the disease itself, but "carries" the defective gene, and thus can pass it on to future offspring. A child who has only one parent with the recessive form of OI has no chance of actually having the disease, but a 50% chance of being a carrier.

Key Terms

Collagen

A fibrous, protein material which makes up skin, bone, cartilage, and ligaments.

Ligament

A fibrous band which serves as a connection between bones. An important part of the joints.

Mutation

A permanent change to the genetic code of an organism. Once established a mutation can be passed on to offspring.

Sclera

The white part of the eye.

Scoliosis

A bending or twisting of the spine.

Further Reading

For Your Information

Books

• Hall, Bryan D. "Inherited Osteoporoses." In Nelson Textbook of Pediatrics, edited by Richard Behrman. Philadelphia: W.B. Saunders Co., 1996.

  Periodicals

• Marini, Joan C., and Naomi Lynn Gerber. "Osteogenesis Imperfecta: Rehabilitation and Prospects for Gene Therapy." Journal of the American Medical Association 277(March 5, 1997): 746+.
• Paterson, Colin, et al. "Life Expectancy in Osteogenesis Imperfecta." British Medical Journal 312(February 10, 1997): 351.
• Wardinsky, Terrance D. "Genetic and Congenital Defect Conditions that Mimic Child Abuse." Journal of Family Practice 41(October 1995): 377+.

  Organizations

• March of Dimes Birth Defects Foundation. 1275 Mamaroneck Avenue, White Plains, NY 10605. http://222.modimes.org.
• Osteogenesis Imperfecta Foundation (OIF). 804 W. Diamond Avenue NW, Suite 210, Gaithersburg, MD 20878. (301) 947-0083. http://www.oif.org.

Gale Encyclopedia of Medicine. Gale Research, 1999.