Osteogenesis imperfecta (OI) is a genetic disorder characterized by bones that break easily, arising from defects that impair the body’s ability to produce strong bones. The core issue lies with collagen, a protein in connective tissues that creates the framework for bone formation. Individuals with OI either produce too little type I collagen or the collagen is of poor quality, resulting in bone fragility. The condition’s effects can range from a few fractures over a lifetime to several hundred.
Prevalence and Incidence
Incidence refers to the rate of new cases, which for OI is estimated to occur in approximately 1 in every 15,000 to 20,000 births worldwide. This highlights its status as a rare genetic disorder.
Prevalence measures the total number of individuals living with the condition at any given time. In the United States, it is estimated that between 25,000 and 50,000 people have OI. The range in this estimate reflects challenges in diagnosing milder forms of the condition that may go undiagnosed.
Breakdown by OI Type
The classification of osteogenesis imperfecta into different types helps describe the wide spectrum of severity and clinical features. The most widely used framework is the Sillence classification, which originally outlined four main types based on clinical observation and inheritance patterns.
Type I OI is the mildest and most common form, accounting for about 50% of cases. Individuals with Type I have a reduced quantity of normal type I collagen, leading to bone fragility but often with little to no bone deformity. Many people with this type experience most of their fractures before puberty. Clinical features often include blue sclerae (the whites of the eyes), and while stature may be shorter than average, it is not typically severe.
Type II is the most severe form and is considered perinatally lethal. Its incidence is estimated at about 1 in 40,000 to 1.4 in 100,000 live births. This form is characterized by extreme bone fragility with numerous fractures occurring before birth, leading to crumpled long bones and poorly mineralized skulls.
Type III OI is a severe, progressively deforming type where individuals are born with fractures and experience ongoing bone deformities. It is less common than Type I but is a severe form compatible with a longer lifespan. People with Type III have poorly formed collagen, resulting in very short stature, spinal curvature, and respiratory problems. Type IV OI presents with moderate severity, falling between Types I and III, and is characterized by normal-colored sclerae.
Demographic and Genetic Patterns
Osteogenesis imperfecta affects individuals across all demographics without prejudice. Statistics show the condition occurs with equal frequency in both males and females. Similarly, there is no reported racial or ethnic predisposition, meaning OI is found in populations worldwide at comparable rates.
Approximately 90% of all cases are caused by a mutation in one of two genes: COL1A1 or COL1A2. The majority of OI cases follow an autosomal dominant inheritance pattern, meaning only one copy of the mutated gene is needed to cause the disorder. For an affected parent, there is a 50% chance of passing the gene mutation to each child.
A significant portion of OI cases, particularly severe forms like Type II and III, arise from a de novo (new) spontaneous mutation, meaning there is no family history of the disorder. Around 10-15% of OI cases result from recessive inheritance. This occurs when a child inherits a copy of the mutated gene from both parents, who are carriers but do not have the condition.
Associated Health Complications
Beyond fragile bones, osteogenesis imperfecta is associated with other health issues. Hearing loss is a common complication, with over 50% of adults with OI Type I experiencing some hearing impairment by age 40. This can be conductive, sensorineural, or mixed, stemming from abnormalities in the small bones of the middle ear or issues with the inner ear.
Dental problems, specifically dentinogenesis imperfecta, are another frequent finding. This condition affects the dentin, causing teeth to be discolored, weak, and prone to rapid wear and breakage. While present in multiple OI types, it is particularly common in more severe forms and relatively uncommon in individuals with Type I OI.
Spinal deformities like scoliosis are also a concern. Moderate-to-severe scoliosis is more prevalent in individuals with Type III OI compared to those with milder forms, though mild scoliosis is observed in 14-20% of individuals across Types I, III, and IV. Other reported complications include joint hypermobility, easy bruising, and cardiovascular issues such as aortic root dilation and problems with heart valves.