Osteogenesis imperfecta or OI (meaning "imperfect bone formation") is a group of inherited disorders that affects the bones and connective tissues. People with this condition are born with a reduced bone mass, which results in fragile bones that break easily.
There are at least eight forms of OI that are distinguished by the severity of the symptoms. Milder cases sometimes go unnoticed until adulthood and may involve only a few bone fractures. In severe cases, the bones are extremely fragile and may fracture frequently, even with no or little apparent cause.
Collagen is the major protein of the body's connective tissue. It is part of the framework around which bones are formed. Most types of OI (about 85%) are caused by a mutation in the gene that produces type 1 collagen. There are many different mutations that can affect this gene. The severity of OI depends on the specific gene mutation, which can cause the body to make either too little or low-quality type 1 collagen. It is estimated that 20,000-50,000 people in the United States have OI.
People with OI may have blue sclera, meaning that the whites of the eyes have a blue tint. They may also have a short stature, hearing loss, restricted physical abilities, breathing problems, and weak teeth. Despite these symptoms, most people with OI live relatively normal lives.
Autosomal dominant disorders, autosomal recessive disorders, blue sclera, brittle bone disease, COL1A1, COL1A2, collagen, connective tissue disorders, CRTAP, LEPRE1, OI, P3H1, prolyl 3-hydroxylase 1.
types of the disease
Type I: Type I osteogenesis imperfecta (OI), or mild OI, is the most common form. Individuals with this form may live a normal lifespan. The main symptoms are decreased collagen levels and easily broken bones, with most fractures occurring before puberty. Other symptoms may include loose joints and muscle weakness, blue sclera (whites of the eyes), triangular face, scoliosis (curved spine), weak teeth, and hearing loss later in life.
Type II: Type II is a severe form that usually leads to death during the first year of life. The cause of death is often improperly formed collagen, breathing problems, numerous broken bones, and severe bone deformity. Symptoms include small stature, underdeveloped lungs, and blue sclera (whites of the eyes).
Type III: Type III is also called severe OI. People with this type have many fractures that may occur before birth. In addition, people with type III may have severe bone deformities and may require a wheelchair. Other symptoms include a short stature, blue sclera (whites of the eyes), loose joints, poor muscle development in the arms and legs, a barrel-shaped rib cage, a triangular face, lung problems, weak teeth, hearing trouble, scoliosis (curved spine), poorly formed collagen, and a shorter life expectancy.
Type IV: Type IV is between type I and type III in severity. Bones break easily with most fractures occurring before puberty. Other symptoms include short stature, mild bone deformity, scoliosis, a barrel-shaped rib cage, a triangular face, weak teeth, hearing loss, and improperly formed collagen. Affected individuals often require braces or crutches to walk but have a normal life expectancy.
Type V: Type V is similar to type IV in appearance and symptoms. A dense band can be seen on X-rays near the growth plate of the arm and leg bones. Unusually large bone deposits can be observed at the sites of fractures. Symptoms include restriction of forearm rotation and bone with a microscopic "mesh-like" appearance.
Type VI: Type VI is similar to type IV in appearance and symptoms. Activity of alkaline phosphatase (an enzyme linked to bone formation) is slightly elevated, which can be measured by a blood test. A bone biopsy will show that bone has a microscopic fish-scale pattern. Very few individuals with this type of OI have been identified in the scientific literature.
Type VII: This type is caused by a mutation in the CRTAP (cartilage-associated protein) gene. Many cases resemble type IV in appearance and symptoms. In fewer cases, the appearance and symptoms are similar to type II, except that infants have white sclera, a small head, round face, short stature, short arm and leg bones, and abnormal hip sockets. Partial function of CRTAP leads to moderate symptoms while total absence of CRTAP causes death.
Type VIII: Type VIII resembles type II or type III in appearance and symptoms except that infants have white sclera and severe growth deficiency. This type is caused by a deficiency of an enzyme called P3H1 (prolyl 3-hydroxylase 1) due to a mutation in the LEPRE1 gene. P3H1 is required for proper collagen formation.