Osteogenisis Imperfecta (OI) is a genetic disorder characterized by bones that break easily, often from little or no
apparent cause. There are now seven recognized types of the disorder, representing extreme variation in severity from
one individual to another. OI is created by mutations in the type I pro-collagen genes. For example,
a person may have just a few or as many as several hundred fractures in a lifetime. It is estimated that there are about
20,000 to 50,000 people with Osteogenesis Imperfecta in the United States. With an incidence of 1 in 15-20,000.
Osteogenesis Imperfecta is caused by a genetic defect that affects the body's production of collagen. Collagen is the major
protein of the body's connective tissue and can be likened to the framework around which a building is constructed. In OI,
a person has either less collagen than normal(TYPE I), or a poorer quality of collagen than normal(all
other TYPES)--leading to weak bones that fracture easily. The characteristics features of Osteogenesis Imperfecta
vary greatly from person to person--even among people with the same type of OI, and not all characteristics are evident in
Clinical Features of Osteogenesis Imperfecta-
(type ordered based on severity from mild to severe)
Type I OI-mild
The most common mutation causing OI Type I causes a reduction in the production of otherwise normal type I collagen secondary
to the effect of a null allele mutation. This means that Type I means too little of "normal" collagen.
Patients often have normal stature but a slightly low stature does not preclude the diagnosis of type I OI. "Type I OI" does
not equal "mild OI". Individuals may have few or no fractures, mostly during the first years of life or even at birth, or
numerous fractures throughout their lives. They may have triangular face but may have normal faces. They are usually
fully ambulatory, and do not have bowing of the long bones, although vertebral fractures may be present. Most have blue
sclera, but it can be white, or the blue color may fade as the individual grows older. This condition is transmitted
as an autosomal dominant trait. Despite the absence of fractures, bone density can be very low, with no correlation with clinical
severity, underscoring the relative lack of significance of bone density measurements assessing severity in patients with
OI. In many instances bone density is normal during the first months of life, and individuals progressively fail to increase
bone mineral density with age. In some cases the diagnosis is an incidental finding after a fracture. Dentinogenesis imperfecta
can be present even in very mild cases. Early hypoacusia and cardio-vascular problems, particularly aortic valvular
disease can be present in these subjects. Most common form of OI. Most fractures occur before puberty. Loose joints
and low muscle tone.
Hearing loss possible, often beginning in early 20s or 30s.
Collagen structure is normal, but
the amount is less than normal.
Type IV-moderate OI with short stature
These individuals typically have short stature, bowing of long bones, and vertebral fractures. Scoliosis and joint laxity
may be present. Patients with this form of OI are generally able to ambulate, but they may require aids for walking. Based
on the presence of DI, moderate OI has been sub-divided in two forms, "a" and "b". These patients have white or bluish sclera.
Precise diagnosis of this type of OI is often difficult, as the clinical characteristics are not clear in the literature,
and different centers base the diagnosis on different criteria.Shorter than average stature. Mild to moderate bone deformity.
Tendency toward spinal curvature.
Barrel-shaped rib cage. Triangular face possible. Brittle teeth possible.
loss possible. Collagen is improperly formed.
Bones fracture easily. Fractures often present at birth, and x-rays may reveal
healed fractures that occurred before birth. Short stature. Barrel-shaped rib cage.
Sclera have a blue, purple,
or gray tint but can be white. Triangular face.
Loose joints and poor muscle development in arms and legs.
curvature. Respiratory problems possible. Bone deformity, often severe. Brittle teeth possible. Hearing
Collagen is improperly formed.
Type II-Lethal until Pamidronate
Most severe form of Osteogenesis Imperfecta.
at or shortly after birth, often due to respiratory problems.
In recent years, some people with Type II have lived into
Numerous fractures and severe bone deformity.
Small stature with underdeveloped lungs. Collagen is
Most cases of Osteogenesis Imperfecta are caused by a dominant genetic defect. Some children with OI inherit the disorder
from a parent. Other children are born with OI even though there is no family history of the disorder. In these children,
the genetic defect occurred as a spontaneous mutation. Because the defect, whether inherited or due to a spontaneous mutation,
is usually dominant, a person with Osteogenesis Imperfecta has a 50 percent chance of passing on the disorder to each of his
or her children. Genetic counselors can help people with OI and their family members further understand OI genetics and the
possibility of recurrence, and assist in prenatal diagnosis for those who wish to exercise that option.