|
|
| DiseaseID |
HGD20 |
| Genetic
Disorder |
Osteogenesis Imperfecta
|
| Gene
Name |
COL1A1 and COL1A2, CRTAP gene |
| Description |
Osteogenesis imperfecta (OI) is a genetic disorder that causes a person's bones to break easily, often from little or no apparent trauma. OI is also called "brittle bone disease." OI varies in severity from person to person, ranging from a mild type to a severe type that causes death before or shortly after birth. In addition to having fractures, people with OI also have teeth problems (dentinogenesis imperfecta), and hearing loss when they are adults. People who have OI may also have muscle weakness, loose joints (joint laxity) and skeletal malformations.
OI occurs in approximately 1 in 20,000 individuals, including people diagnosed after birth. OI occurs with equal frequency among males and females and among racial and ethnic groups. Life expectancy varies depending on how severe the OI is, ranging from very brief (lethal form, OI type II) to average.
There are four well-known types of OI. These types are distinguished mostly by fracture frequency and severity and by characteristic features. Three additional types of OI (type V, VI and VII) have also been identified.
The vast majority (90 percent) of OI is caused by a single dominant mutation in one of two type I collagen genes: COL1A1 or COL1A2.The COL1A1 and COL1A2 genes provide instructions for making proteins that are used to create a larger molecule called type I collagen. This type of collagen is the most common protein in bone, skin and other tissues that provide structure and strength to the body (connective tissues). OI type VII is caused by recessive mutations in the CRTAP gene.
|
| Symptoms |
The following are the most common symptoms for osteogenesis imperfecta (OI). However, each child may
experience symptoms differently. Although symptoms may vary, generally they are used to classify the four
forms of OI, each of which represents varying grades of severity of the condition.
Type I:
• most common
• bones fracture easily
• can usually be traced through the family
• near normal stature or slightly shorter
• blue sclera (the normally white area of the eye ball)
• dental problems
• hearing loss beginning in the early 20s and 30s
• most fractures occur before puberty; occasionally women will have fractures after menopause
• triangular face
• tendency toward spinal curvatures
Type II:
• newborns severely affected; frequently lethal
• usually resulting from a new gene mutation
• very small stature with extremely small chest and under-developed lungs
Type III:
• tend to be isolated family incidents
• fractures at birth very common
• x-ray may reveal healing of fractures that occurred while in the uterus
• severe early hearing loss
• loose joints and poor muscle development in arms and legs
• barrel-shaped rib cage
Type IV:
• can frequently be traced through the family
• bones fracture easily- most before puberty
• normal or near-normal colored sclera
• teeth may or may not be involved
• spinal curvatures
• loose joints
The symptoms of OI may resemble other bone problems or medical conditions
|
| Causes |
The cause of osteogenesis imperfecta (OI) is believed to be due to a genetic defect that causes imperfectly-formed, or an inadequate amount of, bone collagen - a protein found in the connective tissue.
The disorder occurs in one out of 20,000 to one out of 60,000 live births. OI can affect males and females of all races. |
| Diagnosis |
OI is often inherited from an affected parent. The diagnosis of OI is made on the basis of family history and/or clinical presentation. Frequent fractures, short stature, a blue hue to the white part of the eye (blue sclera), teeth problems (dentinogenesis imperfecta) and hearing loss that progresses after puberty may be present.
X-rays are also used to diagnose OI. X-ray findings include fractures that are at different stages of healing; an unexpected skull bone pattern called Wormian bones; and bones in the spine called "codfish vertebrae."
Laboratory testing for OI may include either biochemical testing or DNA-based sequencing of COL1A1 and COL1A2. Biochemical testing involves studying collagens taken from a small skin biopsy. Changes in type I collagen are an indication of OI.
DNA sequencing of COL1A1 and COL1A2 is used to identify the type I collagen gene mutation responsible for the altered collagen protein. DNA testing requires a blood sample for DNA extraction. Both tests are relatively sensitive, detecting approximately 90 percent and 95 percent, respectively, of individuals with the clinical diagnosis of OI. Normal biochemical and molecular testing in a child with OI warrants additional testing of less common collagen genes (CRTAP and P3H (LEPRE1)) responsible for some of the rare recessive forms of OI.
|
| Treatment |
There is currently no cure for OI. Treatment involves supportive therapy to decrease the number of fractures and disabilities, help with independent living and maintain overall health. OI is best managed by a medical team including the child's own doctor, and genetic, orthopedic and rehabilitation medicine. Supportive therapy is unique to each individual depending on the severity of their condition and their age.
Physical and occupational therapies to help improve their ability to move, to prevent fractures and to increase muscle strength are often useful.
Fractures are treated as they would be in children and adults who do not have OI. An orthopedic treatment called intramedullary rodding (placing rods in the bones) is used to help with positioning of legs that helps with more normal functioning when necessary.
A newer treatment with medication called biophosphonates is being used to help with bone formation and to decrease the need for surgery. |
|
|
