Osteogenesis Imperfecta

Question 1

What is the molecular defect in osteogenesis imperfecta?

Answer 1

Defective synthesis of type 1 collagen results in increased tendency for fractures
Mutations in COL1A1 and COL1A2

Question 2

What are the types of OI?

Answer 2

Type 1 (commonest and most often appear in PACES)
- Autosomal dominant
- Limited bone fragility and deformity
- Blue sclera, early hearing loss, joint hypermobility
- No dentinogenesis imperfecta

Type 2
- Autosomal dominant
- Stillbirth or neonatal death
- Multiple rib fractures at birth, dentinogenesis imperfecta

Type 3
- AD or AR
- Severe bone fragility, multiple fractures and disability
- Sclera white or blue
- Dentinogenesis imperfecta

Type 4
- Autosomal dominant
- Variable fragility/disability
- Sclera white
- Joint hypermobility
- Basilar impression of skull
- Dentinogenesis imperfecta

Question 3

Case presentation of OI

Answer 3

1. Kyphoscoliosis
2. Short stature
3. Blue sclerae
4. Multiple scars - previous long bone fractures, corrective surgery
5. Hearing aids - deafness due to otosclerosis
6. Long bone deformities
   - Anterior bowing of humerus, tibia, fibula
   - Lateral bowing of femur, radius, ulna
7. Ligamentous laxity in type 1 and type 4
8. Dentinogenesis imperfecta (brittle teeth) in all types except type 1 (thus usually absent in PACES)

Question 4

Management of OI

Answer 4

1. Multidisciplinary team
2. Patient education
3. Occupational therapy
4. Genetic counselling
5. Hearing aids
6. Analgesia for pain control
7. Vitamin D and calcium supplements
8. Biphosphonates
9. Orthopaedic surgery for scoliosis, fracture

Question 5

Differential diagnosis of OI

Answer 5

Think: hypermobile joints, blue sclerae, kyphoscoliosis - see causes in Marfan syndrome deck

Marfan
EDS
Pseudoxanthoma elasticum
Diamond-Blackfan anaemia
Alkaptonuria
Paget’s disease - skeletal + deafness