Osteogenesis Imperfecta (Brittle Bone Disease)

Osteogenesis imperfecta (OI), also known as brittle bone disease, is a group of genetic disorders characterized by fragile bones that break easily. It is a lifelong condition that affects bone strength and structure, and can also impact teeth, hearing, and stature. The severity of OI can vary widely, ranging from mild forms with few fractures to severe cases with numerous fractures and bone deformities present at birth. Most cases are inherited in an autosomal dominant manner, but some may result from new mutations or follow a recessive inheritance pattern.

OI is classified into several types based on clinical features, severity, and genetic findings. The most common classification includes the following types:

• Type I: Mildest form with normal stature, blue sclerae, and frequent fractures during childhood.
• Type II: Most severe form, often lethal at or shortly after birth, with numerous fractures and underdeveloped lungs.
• Type III: Severe form with progressive bone deformities, short stature, and respiratory complications.
• Type IV: Moderate severity with variable bone deformities and fracture frequency, and often normal sclerae.
• Other rare types (V, VI, VII, VIII, etc.) have distinct genetic causes and additional symptoms.

OI is primarily caused by mutations in the COL1A1 and COL1A2 genes, which encode type I collagen, a major protein in bones and connective tissues. These mutations lead to poor collagen production or structurally abnormal collagen, resulting in fragile bones. Less common forms are linked to mutations in other genes that affect bone development or mineralization.

Symptoms vary by type and severity but typically include frequent bone fractures, bone deformities, short stature, blue or gray sclerae (whites of the eyes), hearing loss, loose joints, muscle weakness, and dental issues such as dentinogenesis imperfecta. In severe forms, fractures may occur before or during birth. Respiratory issues and spinal curvature are also common in severe types.