Basics of osteogenesis imperfecta

Osteogenesis Imperfecta (OI) is a group of inherited disorders in which the most common feature is bones that break easily.

OI results from an alteration either in the chemical makeup or production of collagen. Collagen is the protein "glue" that holds the body's tissues together and gives strength to bones. It is the major protein in bone. There are several types of collagen, and one of the most important is type I collagen.

Prognosis

Most people with OI have a normal life expectancy and lead very productive lives. Most often they can attend regular schools, enjoy a wide range of career and lifestyle choices, experience fulfilling relationships, and have children.

Curability

While there is no cure for OI, early diagnosis and treatment can help ease symptoms and prevent complications.

The main purpose of this page is to provide background information about the diagnosis and treatment of OI. Another purpose is to increase public awareness about this condition. Increased awareness not only can help promote a better understanding of OI, but also can reduce the risk of misdiagnosis resulting in mistaken accusations of child abuse.

Symptoms

There are four distinct types of OI: types I, II, III, and IV.

The type of OI is consistent, or "runs true," in a family. For example, a parent with OI type IV will not have a child with OI type III. The diagnosis of the type of OI is made based upon information obtained from the person's physical examination, family history, and X-ray studies. A skin biopsy often is done. This involves removing a tiny piece of skin, usually from the back of the arm. The skin cells are grown in culture and the collagen is studied.

OI Type I

OI type I is the most common type of OI. It is inherited in an autosomal dominant pattern but may occur as a result of a spontaneous mutation. People with OI type I have an average of 20 to 40 fractures before puberty. Fewer fractures occur after puberty. Prenatal diagnosis often is possible. People with OI type I have one or more of the following features:

• fragile bones
• triangular-shaped face
• blue sclerae (the white part of the eye)
• hearing loss beginning in the teens, twenties, or thirties
• curvature of the spine (scoliosis)
• thin, smooth skin

OI Type II

About 10 percent of people with OI have OI type II. OI type II results from a new mutation. OI type II is a very severe form of OI. Infants with this form of OI have fractures before birth, have extremely fragile bones, and usually die shortly after birth. Prenatal diagnosis is possible.

OI Type III

Approximately 20 percent of people with OI have OI type III. It usually results from a new dominant mutation. These people often have many spontaneous fractures. It is not unusual for a person to have 20 or more fractures occurring during the first three years of life and more than 100 fractures by puberty. Loose joints and poor muscle development are common. Prenatal diagnosis often is possible. Characteristic features include:

• soft bones that not only break but also bend easily
• misshapen arms and legs
• compressed vertebrae and severe curvature of the spine (scoliosis)
• severely misshapen chest that may cause problems with breathing
• poor development of the teeth (dentinogenesis imperfecta), causing teeth to be discolored and to break easily
• mild to severe hearing loss in adult life
• short stature (some people may only grow to be three feet tall)

OI Type IV

OI type IV is inherited in an autosomal dominant pattern, although some people have the disorder as a result of a new dominant mutation. In OI type IV, most fractures occur during childhood, but women often have a recurrence of fractures after menopause. Typical features include:

• pale blue sclerae at birth that become white by adulthood
• curvature of the spine
• loose, easily overstretched joints
• dentinogenesis imperfecta
• mild short stature

Causes

This brief section on heredity may answer some of your questions about what causes osteogenesis imperfecta.

We encourage you to discuss your concerns with a genetic counselor or with a knowledgeable physician. Contact the March of Dimes for a referral to a genetic counseling center in your area.

Remember, parents have no control over which genes they pass on to their children and should not feel at fault if one or more of their children has OI.

To understand OI, it's important to know how genes influence a person's biological makeup. Genes are chemical units of hereditary material that direct the development and function of every cell in the body. Genes determine which features or traits children will inherit from their parents. Genes affect growth, development, and appearance. They also influence one's tendency to get sick or resist disease.

Chromosomes are threadlike parts of cells that carry the genes. Every cell in our body contains 23 pairs of chromosomes, with the exception of reproductive cells (sperm and egg). Reproductive cells each contain 23 unpaired chromosomes. At conception, each parent provides a reproductive cell with one set of chromosomes. The two reproductive cells combine to form a single cell with a full set of chromosomes and corresponding genes.

Most of the body's 50,000 or so genes function normally. Sometimes, however, a gene becomes changed from its original form. This is called a "mutation." If the mutation causes a collagen gene to function improperly, problems with collagen production and structure occur. This, in turn, can cause problems with bone growth or structure and result in OI.

OI usually is inherited in a family in a pattern called autosomal dominant inheritance. Another way OI can be inherited is by autosomal recessive inheritance, which is very rare. OI also can occur for the first time in a child of unaffected parents as a result of a new or "spontaneous" autosomal dominant mutation. (Note that in all types of 0I there is an equal likelihood that boys and girls will be affected.)

Autosomal dominant inheritance is a disorder that affects family members in every generation. This is the most common inheritance pattern. The dominant altered gene overrides the effects of the normal gene. Even when the altered gene is paired with a normal one, the child will have OI. With autosomal dominant inheritance, there is a 50-percent chance with each pregnancy that an affected parent will have a child with OI. However, both parents may contribute the normal gene, resulting in a 50-percent chance that their child will not inherit OI. If both parents have an autosomal dominant form of OI, there is a 75-percent chance they will has a child with OI.

Autosomal recessive inheritance is a pattern in which the disorder is inherited only if both genes of the pair are altered C genes. A child can be affected only if he or she inherits an altered OI gene from each parent. Parents who have one recessive gene are "carriers" (a person who carries the altered OI gene but does not have symptoms of OI). With each pregnancy there is a 25-percent chance that the child will inherit the disorder, a 50-percent chance that the child will be an unaffected carrier like the parents, and a 25-percent chance that the child will inherit the normal gene from both parents and be unaffected. This form of OI is very rare.

New or spontaneous autosomal dominant mutations make it possible for a child to have OI even though neither parent has an altered collagen gene. The affected person then has the same chance to have an affected child as in autosomal dominant inheritance.

Treatment

There is no cure for OI, but various treatments can reduce the severity of symptoms.

Anyone experiencing pain should ask their doctor to check for a fracture or seek advice about appropriate pain management medications and strategies. For some people the solution is a combination treatment program involving muscle-strengthening exercises and the use of adaptive aids. Swimming is recommended because it helps strengthen joints and muscles without undue stress. A number of special aids such as those listed below also can assist in rehabilitative therapy.

Surgery

Most OI fractures heal well. However, they do require close attention to prevent deformities or prolonged disability. If fractures do not heal properly, orthopedic surgery may be needed to correct deformities, particularly of the limbs and spine. Metal rods often are placed inside the long bones of children to correct deformities and to give strength to their arms and legs if they have multiple fractures or if the bones are poorly shaped.

Adaptive aids

People having difficulty walking due to frequent fractures or various physical limitations may be more mobile using crutches, braces, a cane, or a walker. Wheelchairs may be required by some people. Therefore, it's important that excessive weight gain be avoided.

Other adaptive aids and medical procedures are particularly helpful in increasing independence in daily activities and maintaining an optimum level of health. Splints can help stabilize joints. Individuals with hearing loss may benefit from hearing aids. People who have fragile teeth should ask their dentist about capping their teeth early to minimize wear and breakage. Dressing and bathing aids are available through mail-order catalogs. Special reaching devices are available for short-statured people to ensure that they can reach whatever they need.

Individuals with OI must naturally take extra safety precautions. One highly recommended precaution is to wear a medical diagnostic bracelet; it could be a lifesaver. At home, avoid using area or throw rugs because they can cause slips and falls. Install and use handrails on stairs and in bathtubs. Make sure counters and tables have rounded corners. Keep hallways, stairways, and rooms well lit, using night lights wherever necessary. Since even minor bumps or accidents can fracture a bone, take precautions to avoid large crowds, unknowing toddlers, or large dogs.

Aids for Children

Parents should lift and diaper infants with OI with care and be sure to support their limbs at all times. Many parents successfully transport their children on a pillow or a foam pad. Contact the Osteogenesis Imperfecta Foundation for more information.

If you have a child with OI, discuss the symptoms with teachers and other caregivers so they will know that fractures are features of OI and not signs of child abuse. Classmates should be educated to avoid rough play with the child. Contact sports should be avoided. Although OI does not affect intelligence, medical problems and disabilities may present socialization or adjustment problems for children. If such problems occur, try psychological counseling or family therapy.

There are special legal rights to education for children with disabling disorders. For more information, contact the American Juvenile Arthritis Organization, an organization concerned with the issues of arthritis and related diseases in children.

Though children with OI need special protection, they also need to play and have friends. Involve your children in activities they can safely enjoy, and encourage them to be as independent as possible (football or bicycle helmets are good safety precautions). Since hands usually are spared from fractures, activities such as music, art, and computers are good choices.

Resources

People who are severely affected by OI may need a great deal of medical and financial help. Depending upon the severity of their OI, such individuals may be entitled to receive certain government insurance or disability income benefits such as Social Security disability benefits, Supplemental Security Income, Medicare or Medicaid benefits, free or partial-pay care, or general emergency assistance. Contact your Social Security office or county welfare department for more information.

Keep in mind that most people with OI have a normal life expectancy and lead very productive lives. Most often they can attend regular schools, enjoy a wide range of career and lifestyle choices, experience fulfilling relationships, and have children.

• The Arthritis Foundation
• American Juvenile Arthritis Foundation (AJAO), a membership organization of the Arthritis Foundation, 1314 Spring Street N.W, Atlanta, GA 30309 (404) 872-7100
• March of Dimes
• National Organization for Rare Disorders (NORD), P.O. Box 8923, New Fairfield, CT 06812 (203) 746-6518 or toll-free (800) 999-6673
• Osteogenesis Imperfecta Foundation,804 W. Diamond Avenue, Suite 210, Gaithersburg, MD 20878, (301) 947-0083 or toll-free (800) 981-2663, bonelink@oif.org

Condition research

Medical researchers continue to learn more about OI. Researchers are investigating the effect of growth hormone on short-statured children to determine its effects on height and bone quality. They're investigating how mutations in type I collagen genes result in bone brittleness. They're also trying to determine why some of the skeletal symptoms of OI are most severe during childhood, improve during adolescence, and then increase in women after menopause. The ultimate goal of these researchers is to find ways to treat OI more effectively and to cure or prevent it.

Credits

Some of this material may also be available in an Arthritis Foundation brochure. Contact the Washington/Alaska Chapter Helpline: (800) 542-0295. If dialing from outside of WA and AK, contact the National Helpline: (800) 283-7800.

Adapted from the pamphlet originally prepared for the Arthritis Foundation by Meinhard Robinow, MD, and Robin L. Bennett, MS. This material is protected by copyright.