Osteogenesis Imperfecta

Osteogenesis imperfecta is a genetic condition which causes the bones to become weak and break easily. It is sometimes referred to as OI and can have an impact on people in various ways. There are at least four types of the condition which have been identified, though it is the case that some people are more severely affected than others. There are certain people who are fortunate to suffer only a few fractures in their lifetime while others will suffer many more.

Diagnosis

The condition is genetic and associated with abnormal collagen production, which is an important protein found in connective tissue. Those who suffer from osteogenesis imperfecta either have a lack of collagen or a poor standard of collagen, contributing to weaker bones which fracture easily.

In some cases it is possible to identify osteogenesis imperfecta according to symptoms and clinical features. However, further tests are often administered to ensure an accurate diagnosis and determine the severity of the condition. Geneticists can perform tests on the collagen, including DNA tests and biochemical tests, to reach a diagnosis, but it can often take several weeks for the test results to return. The results are highly accurate; both DNA and collagen sample tests can detect around 90 per cent of collagen type 1 mutations.

A positive collagen sample test confirms a diagnosis of osteogenesis imperfecta. If the result is negative it is possible that the patient has either a different form of the condition, or the type 1 mutation is in attendance but has not been detected by the biopsy test. This indicates that the negative collagen sample test does not rule out the possibility of the patient suffering from osteogenesis imperfecta.

Clinical features

The clinical features vary according to the severity of the condition and some people display more severe symptoms than others. The features can also vary between those with the same type of osteogenesis imperfecta. In rare cases symptoms can even vary between members of the same family. General clinical features of the different types of osteogenesis imperfecta include:

Type 1

• This is the most common form of osteogenesis imperfecta
• This is the mildest form of OI
• People with type 1 OI usually have normal stature
• Type 1 OI causes susceptibility to fractures and most suffer from fractures before puberty
• Type 1 OI is caused by poor quality collagen, not a shortage of collagen

Symptoms

• Triangular-shaped face
• Curvature of the spine
• Brittle, weak teeth
• Muscle weakness
• Loose joints
• Hearing difficulties (this usually affects older people and starts at around the age of 20-30)
• Coloured tinge to the whites of the eyes (often purple or blue in colour)

Type II

• Type II OI causes short stature
• Type II OI is caused by abnormal collagen formation
• This is the most severe form of OI
• This form of OI can be fatal at or after birth as a result of breathing problems, but life expectancy is increasing and some people have survived into adulthood in recent years

Symptoms

• Multiple fractures
• Underdeveloped lungs

Type III

• Type III OI is caused by improper collagen formation
• Type III OI causes short stature

Symptoms

• Coloured whites of the eyes
• Triangular-shaped face
• Possibility of hearing loss
• Possibility of respiratory problems
• Weakened muscles
• Curvature of the spine
• Weak teeth
• Possibility of bone abnormality (this can be severe in some cases)
• The rib cage may be barrel-shaped

Type IV

• Type IV OI is caused by improper formation of collagen
• Type IV OI is not as severe as type III OI but more severe than type I OI
• Those with type IV OI are usually shorter than average

Symptoms

• Possibility of bone deformity (this can be mild or moderate)
• Possibility of hearing loss
• Increased susceptibility to fractures (many people suffer fractures before puberty)
• Triangular-shaped face
• Rib cage may be barrel-shaped
• Curvature of the spine
• Coloured whites of the eyes

Researchers have been investigating the different types of osteogenesis imperfecta for many years and during their investigations it was noted that certain people with type IV OI have a specific pattern. Further investigation revealed that different groups of people with this form of OI have characteristics in common. The researchers then decided to classify these groups as V and VI. Patients who have these types of OI do not have mutations in the collagen type 1 genes.

Type V

This type of OI is clinically similar to type IV

Additional features

• Abnormally large calluses at fracture sites (this is known as hypertrophic calluses)
• Normal whites of the eyes
• Normal strength teeth
• The bone tissue appears mesh-like on X-ray images
• Restricted movement of the arms; caused by calcification of the membrane between the bones in the forearm, the ulna and the radius

Type VI

People who have type VI osteogenesis imperfecta may be either moderately or severely affected. The whites of the eyes and teeth will not be affected but other clinical features are similar to milder forms of OI. The only means of distinguishing type VI OI from other forms is a bone biopsy test. The bone tissue has a 'fish-scale' effect which can be seen under a microscope.

Inheritance factors

The majority of osteogenesis imperfecta cases are brought on by the inheritance of a dominant genetic defect, but it is possible for a child to be born with OI if they do not have a parent with the condition. In this case OI is caused by a spontaneous genetic mutation.

The genetic defect is usually dominant, which means that if a person has OI they have a 50 per cent possibility of passing the condition onto any children they have. It can be difficult for those with OI to decide whether or not to have children. However, genetic counsellors are able to help couples make a decision and provide them with emotional support, as well as the information and facts they need to make a well-informed decision. There are also charities that can help those affected by osteogenesis imperfecta.

Treatment

There is currently no cure for OI and treatment simply aims to reduce symptoms and make life more manageable by increasing bone and muscle strength. Those who suffer from OI often use mobility aids and braces to support them, but the following treatments can also prove to be beneficial:

• Physiotherapy
• Fracture care
• Dental care
• Surgery

Rodding is a surgical procedure which involves the insertion of metal rods into the bones to make them stronger and correct abnormalities.

Medications are also being investigated for the treatment of osteogenesis imperfecta.

Exercise is important for people who have osteogenesis imperfecta as exercise helps to build muscle strength and improve mobility. However, it is important that the exercise is appropriate. Trained professionals, including physiotherapists to ensure it is suitable for the individual, will draw up the exercise regime. Swimming is a popular choice for people with OI as there is a low risk of injury and the feeling of the water can be therapeutic.

iet and exercise are also key factors in the maintenance of a healthy, stable body weight. Those with OI should avoid smoking, caffeine and excessive alcohol consumption as these can increase bone fragility.

Prognosis

The prognosis varies greatly depending on the individual case. Some are severely affected by osteogenesis imperfecta causing great compromise in their lives, while many people with OI manage to live long and fulfilling lives.