Type 3 osteogenesis imperfecta is a severe form of osteogenesis imperfecta (OI), also known as brittle bone disease. Its signs and symptoms fall between those of the extremely severe type I OI and the milder type II OI. Mutations in the COL1A1 and COL1A2 genes are usually the cause of type 3 OI. Common features of type 3 include bones that fracture easily, a triangular face, and short stature.

What Is Type 3 Osteogenesis Imperfecta?

Osteogenesis imperfecta (OI), also known as brittle bone disease, is a group of inherited disorders that mainly affect the bones, causing them to be fragile and easily broken. Type 3 osteogenesis imperfecta is a severe form of the disorder; its signs and symptoms fall between the very severe type II osteogenesis imperfecta and the milder type I osteogenesis imperfecta.   Type 3 osteogenesis imperfecta probably has a birth frequency of about 1 in 60,000.  

What Causes It?

Mutations in the COL1A1 and COL1A2 genes cause type 3 osteogenesis imperfecta. The proteins made by COL1A1 and COL1A2 genes are used to assemble larger molecules called type I collagen, the major protein in bones.   Collagens provide structure and strength to connective tissue (the type of tissue that forms a supportive framework for the body's muscles, ligaments, skin, and bones). Mutations in either gene prevent collagen molecules from being assembled correctly. This defect weakens connective tissue, particularly in bone, which causes the bone abnormalities seen in this condition.   In some instances, type 3 osteogenesis imperfecta may result from mutations in other genes that have not yet been identified.  

Inheriting Type 3 Osteogenesis Imperfecta

Type 3 osteogenesis imperfecta can be inherited in either an autosomal dominant or an autosomal recessive pattern. Most cases in North America and Europe are autosomal dominant, which means one copy of the altered gene is sufficient to cause type 3 osteogenesis imperfecta.   Rare cases are autosomal recessive, which means two copies of the gene must be altered to cause the condition. The autosomal recessive form of type 3 osteogenesis imperfecta is much more frequent in eastern Mediterranean and black South African populations, and usually results from mutations in genes other than COL1A1 and COL1A2.