Osteogenesis Imperfecta

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What is osteogenesis imperfecta?

Osteogenesis imperfecta is a group of genetic disorders that mainly affect the bones. The term osteogenesis imperfecta means imperfect bone formation. People with this condition have bones that are brittle and easily broken. Multiple fractures are common, and in severe cases, can occur even before birth.

Researchers have identified several types of osteogenesis imperfecta. The types are often distinguished by their signs and symptoms, although their characteristic features overlap. Increasingly, specific bony changes and genetic factors are also used to define the different types of this condition.

Type I osteogenesis imperfecta, the mildest form of the condition, is characterized by bone fractures during childhood and adolescence that often result from minor trauma. Fractures occur less frequently in adulthood. People with this form of the condition typically have a blue or grey tint to the part of the eye that is usually white (the sclera) and may develop hearing loss in adulthood. Affected individuals are usually of normal or near normal height.

Osteogenesis imperfecta type II is the most severe form of the disorder. Infants with type II have bones that appear bent or crumpled and may fracture before birth. The chest is narrow, with a very small rib cage and underdeveloped lungs. Affected infants have short, bowed arms and legs; dark blue sclerae; hips that turn outward; and unusually soft and thin skull (calvarial) bones. Most infants with type II are stillborn or die shortly after birth, usually from respiratory failure.

People with type III osteogenesis imperfecta have very fragile bones that may begin to fracture before birth. In some cases, rib fractures can cause life-threatening problems with breathing. Bone abnormalities tend to worsen over time and often interfere with mobility. People with this form of the disorder have very short stature; their adult height may be less than 3 feet. Type III osteogenesis imperfecta is also associated with blue sclerae that lighten with age, hearing loss beginning in adolescence, and a disorder of tooth development called dentinogenesis imperfecta.

Osteogenesis imperfecta type IV is a moderate form of the disorder. About 25 percent of affected individuals are born with bone fractures; others may not have any broken bones until later in childhood or adulthood. Although the sclerae may have a bluish tint in infancy, adults with this form of the condition usually have white sclerae. Additional features of type IV osteogenesis imperfecta can include mild short stature, hearing loss, and dentinogenesis imperfecta.

Researchers have proposed several additional types of osteogenesis imperfecta, but in most cases the genetic causes of these types have not been determined.

How common is osteogenesis imperfecta?

This condition affects an estimated 6 to 7 per 100,000 people worldwide. Types I and IV are the most common forms of osteogenesis imperfecta, affecting 3 to 4 per 100,000 people. Types II and III are rarer, with an estimated incidence of 1 to 2 per 100,000 people.

What genes are related to osteogenesis imperfecta?

Mutations in the COL1A1, COL1A2, and CRTAP genes cause osteogenesis imperfecta.

Mutations in the COL1A1 and COL1A2 genes are responsible for about 90 percent of all cases of osteogenesis imperfecta. These genes provide instructions for making proteins that are used to assemble type I collagen, which is the most abundant protein in bone, skin, and other tissues that provide structure and strength to the body (connective tissues).

Most of the mutations that cause osteogenesis imperfecta type I occur in the COL1A1 gene. These mutations reduce the amount of type I collagen produced in the body, which causes bones to be brittle and fracture easily. The mutations responsible for osteogenesis imperfecta types II, III, and IV can occur in the COL1A1 or COL1A2 gene. These mutations typically alter the structure of type I collagen molecules. A defect in the structure of type I collagen weakens connective tissues, particularly bone, resulting in the characteristic features of osteogenesis imperfecta.

Mutations in the CRTAP gene are responsible for rare cases of osteogenesis imperfecta. This gene provides instructions for making a protein that is involved in processing collagen molecules. Mutations in this gene reduce the amount of CRTAP protein or prevent cells from producing any of this protein. As a result, collagen molecules cannot form as they should, weakening connective tissues and leading to the bone abnormalities found in osteogenesis imperfecta.

In cases of osteogenesis imperfecta without identified mutations in the COL1A1, COL1A2, or CRTAP gene, the cause of the disorder is usually unknown.

How do people inherit osteogenesis imperfecta?

Most cases of osteogenesis imperfecta have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition. Many people with type I or type IV osteogenesis imperfecta inherit a mutation from a parent who has the condition. Almost all infants with type II osteogenesis imperfecta have no history of the condition in their family. In these infants, the condition is caused by new (sporadic) mutations in the COL1A1 or COL1A2 gene. The disorder is not passed on to the next generation because affected individuals do not live long enough to have children.

Less commonly, osteogenesis imperfecta can have an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means two copies of the gene in each cell are altered. Most often, the parents of a child with an autosomal recessive disorder are not affected, but each carry one copy of the altered gene. Some cases of osteogenesis imperfecta type III are autosomal recessive; these cases usually result from mutations in genes other than COL1A1 and COL1A2. Rare cases of osteogenesis imperfecta caused by mutations in the CRTAP gene also have an autosomal recessive pattern of inheritance.

Source: National Institutes of Health

New craniosynostosis study findings have been reported by researchers at University of Miami

"Both patients had been treated with ventriculoperitoneal shunts for hydrocephalus. Pfeiffer syndrome had been diagnosed in one of the patients, and the other was suspected to have osteogenesis imperfecta. Although both patients were believed to have symptoms resulting from brainstem compression, posterior fossa decompression was not offered due to profound venous anomalies noted on imaging studies that greatly increased the expected risks associated with surgery," wrote D.I. Sandberg and colleagues, University of Miami.

The researchers concluded: "These cases are presented to alert neurosurgeons to carefully evaluate the posterior fossa venous anatomy prior to considering posterior fossa decompression with or without occipitocervical fusion or calvarial vault remodeling procedures in patients with multisutural craniosynostosis."

Sandberg and colleagues published their study in the Journal of Neurosurgery (Anomalous venous drainage preventing safe posterior fossa decompression in patients with chiari malformation type I and multisutural craniosynostosis. Report of two cases and review of the literature. Journal of Neurosurgery, 2007;106(6 Suppl):490-4).

For additional information, contact D.I. Sandberg, University of Miami Miller School of Medicine and Miami Children's Hospital, Dept. of Neurosurgery, Miami, Florida 33155 USA.

The publisher's contact information for the Journal of Neurosurgery is: American Association Neurological Surgeons, University Virginia, 1224 West Main St., Ste. 450, Charlottesville, VA 22903, USA.

Keywords: United States, Miami, Angiology, Craniofacial, Craniosynostosis, Neurology, Neurosurgery, Synostosis.

This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2007, Pain & Central Nervous System Week via NewsRx.com.