I. Introduction
Osteogenesis imperfecta (OI), also known as “brittle bone disease”, is a group of genetic connective tissue disorders characterized by:
- Bone fragility and multiple fractures,
- Defective connective tissue (due to abnormal collagen type I),
- Extraskeletal features (hearing loss, dentinogenesis imperfecta, blue sclerae).
It is one of the most common inherited bone disorders.
II. Molecular Basis
- Defective synthesis of type I collagen (major structural protein in bone, dentin, sclera, ligaments).
- Mutations most commonly in COL1A1 and COL1A2 genes → abnormal α chains of collagen type I.
- Inheritance: mostly autosomal dominant, but recessive and de novo cases also reported.
Pathogenesis
- Collagen is quantitatively reduced or structurally abnormal.
- Results in weak bone matrix, reduced tensile strength, and systemic connective tissue fragility.
III. Classification (Sillence Classification – major types)
- Type I (Mild)
- Most common and mildest form.
- Normal stature, fractures during childhood (↓ after puberty).
- Blue sclerae (due to thinning of sclera, underlying choroid visible).
- Hearing loss (otosclerosis of middle ear bones).
- Normal life expectancy.
- Type II (Perinatal lethal)
- Most severe form, usually lethal in utero or shortly after birth.
- Multiple fractures, skeletal deformities.
- Extremely fragile bones, underdeveloped lungs.
- Type III (Severe, progressively deforming)
- Severe bone fragility, frequent fractures, progressive deformities.
- Short stature, kyphoscoliosis, barrel-shaped chest.
- Normal sclera (sometimes blue at birth → white with age).
- Wheelchair-dependent, reduced life expectancy.
- Type IV (Moderate severity)
- Variable severity between Type I and III.
- Fractures, mild to moderate bone deformity.
- Normal sclerae.
- May have dentinogenesis imperfecta.