OVERVIEW, SYMPTOMS, & CAUSES

Overview of Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a genetic or heritable disease in which bones fracture (break) easily, often with no obvious cause or injury. OI is also known as brittle bone disease, and the symptoms can range from mild with only a few fractures to severe with many medical complications.

What Happens in OI?

For most people, a change or defect in the genes that carry the instructions for making type I collagen causes OI.  Type I collagen is a material in bones that helps make them strong. The defect in the genes causes the body to make collagen incorrectly or not make enough, leading to weak bones that break more easily. There is no way to prevent the disease.

Who Gets Osteogenesis Imperfecta?

Though anyone can be born with OI, people with a family history of the disease are at greater risk of inheriting the disease through an abnormal gene that is passed on from one or both parents. Genetic counselors can help you better understand the genetics of OI.

Types of Osteogenesis Imperfecta

There are several types of OI, and different classifications are used based on the severity of the disease or on the nature of the underlying gene defect. Type I is the mildest and most common form of OI. Type II is the most severe form of OI. Other types of OI have symptoms that fall between Type I and Type II. Following is an overview of the types most often diagnosed. The remaining types are rare and still being studied.

Type I

  • Bones likely to break from mild to moderate trauma, with most broken bones occurring before puberty.
  • No change or only slight changes to stature with aging.
  • Loose joints and muscle weakness.
  • Blue, purple, or gray tint to sclera (whites of the eyes).
  • Triangular face.
  • Curved spine with potential for compression of the vertebrae (spine bones) with aging.
  • Mild or no bone deformity.
  • Possible changes to the strength and color of teeth.
  • Possible hearing loss.
  • Normal collagen structure, but less than the normal amount.

Type II

  • Frequently causes death at birth or shortly after, because of the inability to breathe.
  • Numerous broken bones that develop before birth while the baby is still in the womb.
  • Severe bone deformities.
  • Very small stature.
  • Underdeveloped lungs.
  • Blue, purple, or gray tint to sclera.
  • Improperly formed collagen.

Type III

  • Most severe type among those who survive the neonatal period and usually results in the greatest number of physical disabilities.
  • Easily broken bones with very little trauma over a lifetime. (Broken bones are often present at birth, and x-rays may reveal healed bone breaks that occurred before birth.)
  • Small stature.
  • Blue, purple, or gray tint to sclera.
  • Loose joints.
  • Poor muscle development in arms and legs.
  • Barrel-shaped rib cage.
  • Triangular face.
  • Curved spine and compression or collapse of vertebrae.
  • Possible lung problems that worsen with age.
  • Often severe bone deformity.
  • Possible changes to the strength and color of teeth.
  • Possible hearing loss.
  • Improperly formed collagen.

Type IV

  • Bones break easily, sometimes before birth, with most broken bones occurring before puberty.
  • Smaller than average stature.
  • White or blue tint to sclera.
  • Mild to moderate bone deformity.
  • Vertebra compression or collapse.
  • Barrel-shaped rib cage.
  • Triangular face.
  • Possible changes to strength and color of teeth.
  • Possible hearing loss.
  • Improperly formed collagen.

Type V

  • Clinically similar to Type IV OI in appearance and symptoms.
  • A dense band seen on x-rays by the cartilage growth plate of the long bones.
  • Unusually large calluses, called hypertrophic calluses, at the sites of fractures or surgical procedures. (A callus is an area of new bone that is laid down at the fracture site as part of the healing process.)
  • Calcification of the membrane between the radius and ulna (the bones of the forearm), which results in restricted arm movement.
  • Possible loose joints.
  • White sclera.
  • No changes to teeth.
  • “Mesh-like” appearance to bone when viewed under the microscope.
  • Changes in the minerals in the bone.

Type VI

  • Resembles Type IV OI in appearance and symptoms.
  • Not always diagnosed at birth, and symptoms progress over time.
  • “Fish-scale” appearance to bone when viewed under the microscope.
  • Curved spine.
  • Diagnosed by bone biopsy or genetic studies.
  • Changes in the minerals in the bone.

Type VII

  • Resembles Type II and Type III OI in appearance and symptoms.
  • White sclera.
  • Small stature.
  • Short humerus (upper arm bone) and short femur (upper leg bone).
  • Possible smaller head size.
  • Changes in the process of forming collagen.

Type VIII

  • Resembles Type II and Type III OI in appearance and symptoms.
  • White sclera.
  • Small stature.
  • Short humerus (upper arm bone) and short femur (upper leg bone).
  • Possible smaller head size.
  • Changes in the process of forming collagen.

There are rarer types of the disease, and in general they are moderately severe forms. These types are similar to OI types III or IV. Some of these rare forms do not affect the structure of collagen but instead affect the function of bone-forming cells.

Symptoms of Osteogenesis Imperfecta

All people with OI have weak, brittle bones. Some people with OI may have only a few broken bones over their lifetime. Others may have hundreds of broken bones in their lifetime, including broken bones that occur before birth.

People with OI may have other symptoms, which can range from mild to severe and vary from person to person. These include:

  • Malformed or bowing of long bones.
  • Small stature.
  • Skin that bruises easily.
  • Loose joints.
  • Weak muscles.
  • Whites of the eyes (sclera) that look blue, purple, or gray.
  • A face shaped like a triangle.
  • A rib cage shaped like a barrel.
  • A curved spine.
  • Collapse or compression of the vertebrae in the spine.
  • Brittle, misshapen, or discolored teeth.
  • Hearing loss.
  • Breathing problems.
  • A deformed hip joint in which the neck of the femur is bent downward, a condition called coxa vara.

Causes of Osteogenesis Imperfecta

A mutation or change in a gene causes OI. Genes carry information that determines which features are passed to you from your parents. We have two copies of most of our genes, one from each parent.

People with OI have a gene that carries incorrect instructions for making collagen, a substance that makes bones strong. The gene causes the body to not make enough collagen or the collagen does not work properly. This leads to weak bones that break easily.

Most people with OI inherit this gene from one parent. In other forms, the child has to inherit a mutation in a gene from both parents. Parents do not have to have OI to pass on the gene that causes it. Sometimes, neither parent passes on the gene. Instead, the gene stops working properly on its own before the child is born.

Dominant OI

Most people with OI have a dominant form. This means they inherit one normal copy and one copy of the gene that causes OI. The abnormal copy of the gene is stronger or “dominant” over the normal copy of the gene. This causes a person to have OI. A person with a dominant mutation has a 50-percent chance (1 in 2) of passing on the disorder to each of his or her children. Some children with the dominant form of OI inherit a gene that causes OI from a parent. While others are born with the dominant form of OI even though there is no family history of the disorder and the mutation occurs in their genome for the first time in the family.

Recessive OI

Some people with OI have a recessive form of the disease. People with recessive OI have parents who do not have OI but who both have an abnormal gene that causes the disease. When both parents carry the recessive gene for OI, there is a 25% chance (1 out of 4) per pregnancy of having a child with the disease. Unaffected or asymptomatic siblings of a person with recessive OI have a two-thirds chance (2 out of 3) of carrying an abnormal gene that causes OI, making them carriers of the disease. If one parent has OI because of a recessive mutation, all of their children will carry an abnormal gene that causes OI but will not necessarily have OI.

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