Osteogenesis Imperfecta
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Direct answer
Osteogenesis imperfecta is a heritable disorder of type I collagen that makes bones brittle, so fractures occur with minimal trauma. Blue sclerae, dentinogenesis imperfecta, joint laxity and conductive hearing loss are common additional features. Most cases are autosomal dominant, and bisphosphonates reduce fracture frequency in children, although they do not correct the underlying defect.
What you must remember
- Basic defect: mutations in COL1A1 or COL1A2 reduce or alter type I collagen, the main collagen of bone, skin, tendon and sclera.
- Inheritance: most cases are autosomal dominant, and a minority of severe forms are autosomal recessive.
- Blue sclerae: the thin sclera lets the underlying choroid show through, and it is typical of type I disease.
- Teeth: dentinogenesis imperfecta gives opalescent, brown-grey teeth that wear quickly.
- Hearing: conductive hearing loss, often from stapes fixation, usually appears in adolescence or early adulthood.
- Radiology: generalised osteopenia, thin cortices, Wormian bones in the skull and bowing of long bones.
- Fractures: they occur with little trauma, and their frequency often falls after puberty in type I disease.
- Treatment: intravenous bisphosphonates such as pamidronate lower fracture rate and bone pain, and intramedullary rodding helps severe deformity.
Grading the severity of collagen defects
A child with recurrent fractures and blue sclerae raises the question of how severe the disease is, not only whether it is present. The Sillence classification grades osteogenesis imperfecta by clinical severity, and the table below summarises its four types.
| Sillence type | Severity | Key features |
|---|---|---|
| Type I | Mild | Blue sclerae, few fractures, near-normal stature |
| Type II | Perinatal lethal | Multiple intrauterine fractures, severe rib and limb deformity |
| Type III | Severe, deforming | Progressive bowing, short stature, sclerae blue early and whiter later |
| Type IV | Moderate | White or grey sclerae, variable deformity |
Types I and IV are the forms most often seen in outpatient practice, while type II usually proves fatal in the perinatal period. Severity also depends on the mutation, because glycine substitutions in the collagen triple helix generally cause more severe disease than null alleles that reduce collagen output.
Clinicians therefore combine the Sillence type with genetic findings when counselling families about prognosis. In an autosomal dominant family, each child of an affected parent has a 50 per cent risk, although many cases arise from new mutations.
Where the question paper misleads
Questions on this condition test whether you can separate a genetic bone disorder from non-accidental injury and from treatment myths. Each trap below pairs a tempting wrong answer with the reasoning that corrects it.
- Trap: choosing non-accidental injury when blue sclerae and a family history are present. Correct: osteogenesis imperfecta explains the picture, so a genetic bone disorder is the likely diagnosis, though abuse must still be excluded where the history is suspicious.
- Trap: picking bisphosphonates as a cure. Correct: they lower fracture frequency and bone pain, but the collagen defect persists, so physiotherapy and orthopaedic care stay essential.
- Trap: diagnosing osteogenesis imperfecta from blue sclerae alone. Correct: blue sclerae are physiological in many infants, so fracture history with genetic or collagen testing confirms the diagnosis.
Frequently asked questions
Which genes are most often mutated in osteogenesis imperfecta?
Mutations in COL1A1 and COL1A2, which encode the chains of type I collagen, cause most cases of osteogenesis imperfecta. Genetic sequencing identifies the variant in most affected children. Glycine substitutions tend to produce more severe disease than null variants.
Why is bisphosphonate treatment used in osteogenesis imperfecta?
Bisphosphonates such as pamidronate reduce bone resorption, which increases bone density and lowers the fracture rate in children with osteogenesis imperfecta. They also relieve bone pain. They do not correct the underlying collagen defect, so orthopaedic support remains necessary.
Which investigation helps distinguish osteogenesis imperfecta from child abuse?
Genetic testing for COL1A1 and COL1A2 variants, together with a full skeletal survey and clinical review, helps separate osteogenesis imperfecta from non-accidental injury. Blue sclerae, Wormian bones and dentinogenesis imperfecta support the diagnosis when they are present.
What dental feature is typical of osteogenesis imperfecta?
Dentinogenesis imperfecta is the typical dental feature, with opalescent brown-grey teeth that wear down quickly. It can affect both primary and permanent dentition. Early dental review is needed to protect the teeth and manage sensitivity.
Which form of osteogenesis imperfecta is usually lethal in the perinatal period?
Sillence type II is the form usually lethal in the perinatal period, with multiple intrauterine fractures and severe rib deformity that cause respiratory failure. Type II is often caused by new dominant mutations, so an unaffected parent does not exclude the diagnosis.