Osteogenesis imperfecta (OI) is a group of genetic diseases in which the
bones are formed improperly, making them fragile and prone to breaking.
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
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
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
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.
OI type I is the most common and mildest type. Among the common features
of type I are the following:
Sometimes called the lethal form, type II is the most severe form of OI.
Among the common features of type II are the following:
Among the common features of type III are the following:
OI type IV falls between type I and type III in severity. Among the common
features of type IV are the following:
Parents should contact a healthcare professional if their child exhibits
any of the symptoms of OI, particularly a tendency to fracture bones
It is often possible to diagnose OI solely on clinical features and x-ray
findings. Collagen or DNA tests may help confirm a diagnosis of OI; test
results may take several weeks to confirm. Approximately 10 to 15 percent
of individuals with mild OI who have collagen testing, and approximately 5
percent of those who have genetic testing, test negative for OI despite
having the disorder.
Diagnosis is usually suspected when a baby has bone fractures after having
suffered no apparent injury. Another indication is small, irregular,
isolated bones in the sutures between the bones of the skull (wormian
bones). Sometimes the bluish sclerae serve as a diagnostic clue.
Unfortunately, because of the unusual nature of the fractures occurring in
a baby who is not yet mobile, some parents have been accused of
before the actual diagnosis of osteogenesis imperfecta was reached.
Testing is available to assist in prenatal diagnosis. Women with OI who
become pregnant or women who conceive a child with a man who has OI may
wish to explore prenatal diagnosis. Because of the relatively small risk
(2–4%) of recurrence of OI type II in a family, families may opt
for ultrasound studies to determine if a developing fetus has the
Ultrasound is the least invasive procedure for prenatal diagnosis and
carries the least risk. Using ultrasound, a doctor can examine the
fetus's skeleton for bowing of the leg or arm bones, fractures,
shortening, or other bone abnormalities that may indicate OI. Different
forms of OI may be detected by ultrasound in the second trimester. When OI
occurs as a new dominant mutation and is found inadvertently on
ultrasound, it may be difficult to confirm the diagnosis until after
delivery since other genetic conditions can cause bowing and/or fractures
Chorionic villus sampling is a procedure that obtains a sampling of cells
from the placenta for testing. Examination of fetal collagen proteins in
the tissue can reveal information about the quantitative or qualitative
collagen defects that leads to OI. When a parent has OI, it is necessary
for the affected parent to have the results of his or her own collagen
test available. Chorionic villus sampling can be performed at ten to 12
weeks of pregnancy.
is a procedure that involves inserting a thin needle into the uterus,
into the amniotic sac, and withdrawing a small amount of amniotic fluid.
Genetic material can be extracted from the fetal cells contained in the
amniotic fluid and tested for the specific mutation known to cause OI in
that family. This technique is useful only when the mutation causing OI in
a particular family has been identified through previous genetic testing
of affected family members, including previous pregnancies involving a
baby with OI. Amniocentesis is performed at 16 to 18 weeks of pregnancy.
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 caused by OI. Splints, casts, braces, and rods are all
used. Rodding is a surgical procedure in which a metal rod is implanted
within a bone (usually the long bones of the thigh and leg). This surgery
is performed when bowing or repeated fractures of these bones has
interfered with a child's ability to walk.
Other treatments include hearing aids and early capping of teeth. Patients
may require the use of a walker or wheelchair.
may be treated with a variety of medications.
is encouraged as a means to promote muscle and bone strength. Swimming is
a form of exercise that puts a minimal amount of strain on muscles,
joints, and bones. Walking is encouraged for those who are able.
Alternative treatment such as acupuncture, naturopathic therapies,
hypnosis, relaxation training, visual imagery, and biofeedback have all
been used to try to decrease the constant pain of fractures.
, excessive alcohol and
consumption, and steroid medications may deplete bone and exacerbate bone
The lifespan of people with OI types I, III, and IV is not generally
shortened. The prognosis for people with these types of OI is quite
variable, depending on the severity of the disorder and the number and
severity of the fractures and bony deformities.
Fifty percent of all babies with OI type II are stillborn. The rest of
these babies usually die within a very short time after birth. In the
early 2000s, some people with type II have lived into young adulthood.
As a congenital birth defect, OI cannot be prevented. Individuals at risk
of having a child with OI should be encouraged to undergo genetic
counseling to more accurately determine their chances of having a child
with OI. The risk of fractures can be minimized with bone- and
muscle-strengthening exercises, rehabilitative therapy, and use of leg
Because the symptoms of OI are caused by collagen abnormalities and not a
calcium deficiency (such as in osteoporosis), supplementation of
will not cure the disease. To prevent bone loss related to calcium
deficiency, which could exacerbate the fragility of bones, it is important
that children with OI consume an adequate amount of calcium (generally 500
mg for children ages one to three, 800 mg for children ages four to eight,
and 1,300 mg a day for preteens and teenagers).
—A microscopic thread-like structure found within each cell of
the human body and consisting of a complex of proteins and DNA. Humans
have 46 chromosomes arranged into 23 pairs. Chromosomes contain the
genetic information necessary to direct the development and functioning
of all cells and systems in the body. They pass on hereditary traits
from parents to child (like eye color) and determine whether the child
will be male or female.
—The main supportive protein of cartilage, connective tissue,
tendon, skin, and bone.
—A type of tough, fibrous tissue that connects bones or cartilage
and provides support and strength to joints.
—A permanent change in the genetic material that may alter a
trait or characteristic of an individual, or manifest as disease. This
change can be transmitted to offspring.
—The tough, fibrous, white outer protective covering of the
—An abnormal, side-to-side curvature of the spine.
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Children's Brittle Bone Foundation.
7701 95th St., Pleasant Prairie, WI 53158. Web site:
Osteogenesis Imperfecta Foundation.
804 W. Diamond Ave., Suite 210, Gaithersburg, MD 20878. Web site:
National Institutes of Health Osteoporosis and Related Bone
Diseases—National Resource Center
, July 2004. Available online at http://www.osteo.org/oi.html
(accessed January 16, 2005).