Osteogenesis imperfecta: the type I collagen disease
- Lesion
Faulty type I collagen makes bones that snap with little force, plus blue sclerae, loose joints, poor teeth and hearing loss.
What it is
Osteogenesis imperfecta is a group of inherited disorders of type I collagen, the main protein of bone matrix, also found in skin, sclera, tendons, ligaments and dentin. Most cases are autosomal dominant mutations of COL1A1 or COL1A2 that either lower the amount of normal collagen or make abnormal chains that poison the triple helix. The result is too little bone, thin cortices and fractures from minor trauma, ranging from a mild adult form to death in the womb. Other matrix diseases of the skeleton involve type II collagen (cartilage and vitreous) and type X collagen (growth plate).
Structure
- Bone is osteopenic: thin cortices and few, slender trabeculae.
- Woven bone persists where lamellar bone should be; osteoblasts may be numerous but lay down little normal matrix.
- Severe forms show crumpled, short long bones from fractures healed in utero.
- Sclerae look blue because thin collagen lets the choroid show through.
- Teeth are translucent and wear down quickly (dentinogenesis imperfecta).
Step by step
- Type I collagen is made of two α1 chains and one α2 chain that wind into a triple helix with glycine at every third position.
- A null allele halves the collagen made but what is made is normal: mild disease.
- A glycine substitution in one chain disrupts every helix that includes it: the dominant-negative effect.
- Abnormal procollagen is retained and degraded; the matrix that forms is scant and poorly mineralized.
- Bone mass and strength fall, and minor trauma breaks bones.
Main clinical types of osteogenesis imperfecta
| Type | Collagen defect | Severity | Key features |
|---|---|---|---|
| I | Less normal collagen (null allele) | Mild, normal lifespan | Fractures in childhood, blue sclerae, hearing loss in adults |
| II | Abnormal chains (dominant negative) | Lethal perinatally | Many fractures in utero, very short crumpled limbs |
| III | Abnormal chains | Severe, progressive deforming | Short stature, bowing, scoliosis, sclerae often become white |
| IV | Abnormal chains | Moderate | Fractures and bowing, normal or greyish sclerae |
Clinical notes
- Presents as fractures with little trauma, bowing, short stature and early hearing loss (otosclerosis-like fixation of the ossicles).
- Bisphosphonates are used in children to increase bone mass; orthopaedic rodding corrects bowing.
- When a child has many fractures, the team considers osteogenesis imperfecta and abuse together; genetic testing helps separate them.
Test yourself
Think of the answer, then tap the question to see it.
Which collagen is defective in osteogenesis imperfecta?
Type I collagen, usually from mutations in COL1A1 or COL1A2.
Why are the sclerae blue?
The scleral collagen is thin, so the underlying choroid shows through.
Why are glycine substitutions more severe than null alleles?
Abnormal chains enter and ruin triple helices (dominant negative), while a null allele only halves the normal collagen.
Which type of osteogenesis imperfecta is lethal around birth?
Type II.
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Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Osteogenesis imperfecta: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025); Osteogenesis imperfecta: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); Ehlers-Danlos syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.