Brittle bone disease
Osteogenesis imperfecta is a congenital (present from birth) condition of abnormal fragility of the bones.
Causes, incidence, and risk factors
This bone disorder is usually present at birth as an inherited disease. Osteogenesis imperfecta (OI) is classified into four major types (and further subtypes).
All four types of OI are caused by defects in the amount or structure of type 1 collagen, an important part of the bone matrix. The collagen problem usually results from a dominant genetic defect. This defect may be acquired by several different mechanisms:
- The defect may be inherited in an autosomal dominant pattern from an affected parent. This means that a parent with a single gene for OI has a 50% chance of having a child with the disorder. Any child who inherits this gene will be affected.
- The defect may be acquired by a spontaneous mutation occurring in the individual egg or sperm that formed the child. In this case, neither parent carries a gene for the disorder or is affected by it. The parents, in this case, are no more at risk than the general population for having another child with the disorder.
- The defect may be acquired through a pattern of inheritance called mosaicism. This occurs when neither parent is affected, but one carries a percentage of sperm or eggs which contain the genetic defect. Therefore, though the parents are unaffected, some of their children may have the disorder and others will not. It is estimated that about 2% to 7% of unaffected parents who have had a child with OI will have another child with OI due to the phenomenon of mosaicism.
All of the bones are abnormally weak in a person with OI. The severity of the abnormality varies enormously - from type 2 OI, which is usually lethal in infancy (or even before birth) to type 1 OI, which may be so mild that the diagnosis is not made, even in adulthood.
The three classic symptoms of OI includes fragile bones, early hearing loss, and whites of the eyes that appear bluish (blue sclerae). Nevertheless, not all people with OI will have blue sclerae or hearing loss. All do have fragile bones, but not all people with OI will ever break a bone.
A variety of other symptoms may be found in the various types of OI:
- Bone fracture (broken bone) o More than one broken bone occurring in a single episode (multiple) o Fractures present at birth o Occuring after only minor trauma
- Deformed or short extremities (such as leg deformities or arm deformities)
- Deafness (conductive hearing loss may occur in adolescents and adults)
- Short stature
- Tooth abnormalities
- Low nasal bridge
- Pectus carinatum
- Pectus excavatum
- Pes planus (flat feet)
- Joint laxity
- Easy bruising
- Bowed legs
Signs and tests
A physical examination may confirm the presence of fractures, deformities, and other symptoms.
Bone x-rays may show multiple healed fractures.
The diagnosis is made by collagen studies done on a skin punch biopsy. Once the specific molecular diagnosis is known, family members can be tested by a DNA blood test. DNA testing on prenatal chorionic villus samples (CVS) can make the diagnosis during pregnancy.
Severe OI is visible on prenatal ultrasound as early as 16 weeks.
Fractures must be repaired quickly in the usual ways to avoid deformities. There is no specific treatment for the underlying disease. However, there are several therapies that may improve the quality of life for patients with OI:
1. Good nutrition and directed exercise is key in helping to optimize bone and muscle strength. Physical rehabilitation and therapy can be quite beneficial. Swimming is an excellent conditioning exercise for many people with OI.
2. Surgical procedures, including the placement of metal rods through bones, can help strengthen bones and prevent deformity. Braces and walking aids are helpful for some.
3. The use of biphosphonates in children with OI is currently being researched with some promising results. Other medical interventions - including bone marrow transplant, the use of growth hormone, and gene therapy - are also under investigation.
Permanent deformity of the extremities may occur. Brain damage may result from skull fractures. The disorder can be fatal. The disease is grouped by type:
- Type 1 - Mild - Compatible with normal life expectancy.
- Type 2 - Lethal - Most, but not all, die in early childhood.
- Type 3 - Progressive deforming - Decreased life expectancy.
- Type 4 - Moderately severe - Compatible with normal life expectancy.
- Recurrent pneumonia
- Heart failure (cor pulmonale)
- Brain damage
- Permanent deformity
- Breathing problems
- Hearing loss
Calling your health care provider
This disorder is often diagnosed at birth, but mild cases may not be detected until later in life. Call for an appointment with your health care provider if symptoms suggestive of this disorder occur.
Genetic counseling is recommended for prospective parents if one or both are affected by this disorder.
by Harutyun Medina, M.D.