Over the past years, genetic disorders have been taking a toll on the lives of the people affected. One of the most debilitating genetic disorder is osteogenesis imperfecta (OI) or otherwise known as brittle bone disease. The term osteogenesis imperfecta means “imperfectly formed bones.”
Osteogenesis imperfecta is a genetic disorder wherein the bones are very weak and may break with little or no trauma. OI is caused by a genetic defect that affects the non-mineral part of the bone. This is a lifelong condition that varies in severity, depending in which it affects – bone quality or bone mass. As a result, children with this condition may have problems with stature hearing, their blood vessels, skin, muscle mass, and teeth.
In the United States, the number of individuals with OI is still unknown. However, the best estimate suggests a minimum of 20,000, and possibly as many as 50,000 people living with OI.
Type 1 OI is the most common type and the mildest form. The bones are predisposed to fracture, and these happen before puberty. The people with this type of OI has normal to near-normal stature but has loose joints and muscle weakness.
In the future, they may have hearing loss, which begins in their 20s and 30s. They have blue, purple or gray tint on the white part of the eye. In some cases, there is just minimal or absent bone deformity while others have possible brittle teeth. They have normal collagen structure.
Type 2 OI
Type 2 OI is the most severe type with causes of death happening at birth or shortly after. Mostly, the cause of death is respiratory problems. They also have blue, gray or purple tinted sclera and various fractures. The Severe bone deformity is also prominent. Their collagen is improperly formed.
Type 3 OI
Type 3 OI is the most severe type among those who survived neonatal period. Those with this type of OI have easily fractured bones, small stature, barrel-shaped rib cage, spinal curvature and possible respiratory problems. They have improperly formed collagen.
Type 4 OI
Those with type 4 OI have easily fractured bones and most of these happen before puberty. They have smaller than average stature, and the severity is between type 1 and type 3. The sclera or white of the eye is normal in color, and they have mild to moderate bone deformity. Like type 3, they can also have barrel-shaped ribs, possible brittle teeth, possible hearing loss and improperly formed collagen.
The symptoms of OI can range depending on the type and severity of the disease. However, the most common symptoms include:
Most of the cases of osteogenesis imperfecta, about 85 to 90 percent, are caused by a dominant genetic defect in one of two type 1 collagen genes – COL1A1 or COL1A2. These genes provide instruction for producing proteins that are used to make a larger molecule dubbed as type 1 collagen. This type of collagen is the most abundant protein in the bone, skin and other tissues that provide strength and structure to the body, like connective tissues.
A person with a form of OI caused by a dominant mutation has a 50 percent risk of passing on the disorder to each of his or her children. However, in some cases, other children born with the dominant form of OI has no family history of the disorder. A spontaneous mutation has led to the emergence of the genetic defect.
About 10 to 15 percent of other cases of OI result from a recessive mutation. This means that the parents do not have OI but are carriers of the faulty genes. For their kids to have OI, they must receive a copy of the mutation from both parents.
OI is a connective tissue disorder that results from the defective synthesis of a protein called collagen, the structural component of bones, tendons, organs, skin, and eyes. There are two risk factors involved in the development of OI:
- Genetic predisposition to the disease
- Family history of the disorder
Most of the patients with severe OI are more susceptible to the various complications. These complications, like respiratory and neurological problems, are the cause of deaths in OI patients.
The most common complications of this disorder include:
- Respiratory problems
- Hearing loss
- Skull fractures
- Brain damage
- Intracranial bleeding
- Brainstem compression
- High risk for complications of anesthesia
- Malignant hyperthermia during anesthesia
- Tooth abnormalities
- Short stature
- Pathological fracture
- Hypotonia or skeletal muscle
- Collagen disorder
- Mitral valve incompetence
- Joint hypermobility
To diagnose osteogenesis imperfecta, the doctor will conduct a complete physical examination and medical history interview with the parents of the child.
Osteogenesis imperfecta is suspected in children who have repeated fractures or whose bones break easily even with very little force. The physical examination will reveal the blue tint on the white of the child’s eyes, short stature and possible scoliosis.
To confirm the diagnosis, a skin punch biopsy will be conducted. Moreover, the family may have a DNA blood test and chorionic villus sampling during pregnancy to determine if the baby has the condition, especially when the parents have a history of the disease.
Usually, when the fetus has type 2 OI, which is the most severe form, this can be seen via an ultrasound when the fetus is as young as 16 weeks AOG.
Today, there is still no cure for osteogenesis imperfecta. However, specific therapies can help reduce the pain and prevent the complications associated with OI. These treatment options have improved the quality of life of people with OI, especially the children and teenagers.
These measures include extensive surgical procedures, care of the fractures and physical therapy. For those with severe deformities, the use of assistive devices and mobility aids such as wheelchairs, braces, and crutches are recommended.
The doctors may prescribe drugs like bisphosphonates, which are used to treat osteoporosis. They may help reduce the symptoms, especially in children. These drugs work by increasing the density and strength of the bones but should only be taken as prescribed by a licensed doctor.
Scientists are now studying and exploring new medications and treatments for OI. However, these treatments have not been proven yet, and they need to conduct clinical trials. These include growth hormone treatment, gene therapies, and other experimental procedures.
To improve the quality of life of those with OI, many benefit from low impact exercises like swimming to keep their bones and muscles strong. For those with severe deformities, reconstructive surgery may be needed. These deformities include bowed legs or a spinal problem.
Children with OI will benefit from a healthy weight, avoiding activities that will harm the body such as alcohol, smoking and caffeine consumption, and eating a nutritious diet. Regardless of the treatment, fractures will always occur, but they heal quickly.
Casts are recommended but not for a long period since disuse osteoporosis is common in people with OI. This is the term used for bone loss when the part of the body isn’t used for a long time.
Providing safety is also important in people with OI. Making sure the house is handicapped-friendly and accessible for people with assistive mobility devices is necessary.
The prognosis or outlook for people with OI greatly depends on which type they have. Also, it depends on the number of deformities or symptoms they have. One of the most common causes of death is a respiratory failure and accidental trauma. However, the good news is, people with OI have the same life expectancy as that for the healthy population, except for those with severe OI that has respiratory and neurologic complications.
Despite suffering from numerous fractures, limited activity and small stature, most children, and adults with OI lead successful and productive lives. They normally live, attend school, develop friendships and relationships, raise families and have careers.
The modern holistic and multidisciplinary treatment has dramatically improved the quality of life and mobility of children and teens with severe OI. The lifespans are also increasing, making them more likely to live to adulthood.
People with OI benefit from counseling and social support, especially when children enter adolescence and might experience low self-esteem and lack of confidence. Support from family and friends is important to make them feel accepted and loved.
With the multidisciplinary treatment options, social support, medical support, and emotional support, the people with OI will have a better quality of life despite the pain and deformity they have. The most important thing to provide is support and safety, especially around the house because accidents can happen anytime. For normal people, a simple fall or slip might cause nothing but a scratch. However, in patients with OI, even these small accidents should be avoided because they can cause permanent deformity, fractures, and debilitating complications.