Osteogenesis Imperfecta

Description

Osteogenesis imperfecta (OI), also known as brittle bone disease, is a rare group of phenotypically related genetic disorders of connective tissues caused by an abnormality in the synthesis or processing of type I collagen. It is characterised by osteoporosis and increased susceptibility to bone fractures. 

Pathophysiology

Frameshift mutation (involving premature stop codon in the affected allele) in the COL1A1 and COL1A2 genes, which encode the α1 and α2 polypeptide chain, result in a qualitative and quantitative decrease in structurally normal type I collagen. 

Depending on the type, the inheritance of the disorder can be autosomal dominant (>95%), autosomal recessive (<10%) or by sporadic mutation.

Clinical Features

• Osteoporosis with abnormal bone fragility
• Blue sclera – due to translucent sclera permitting visualisation of the underlying choroid
• Dentinogenesis imperfecta – due to dentin deficiency
• Hearing impairment – due to impeded conduction from abnormal middle and inner bones

Radiological Features

General

• Severe osteoporosis – DEXA T-score ≤ -2.5
• Deformed, gracile (overtubulated) bones
• Cortical thinning
• Hyperplastic callus formation
• Popcorn calcification: the metaphyses and epiphyses exhibit numerous scalloped radiolucent areas with sclerotic margins
• Zebra stripe sign: cyclic bisphosphonate treatment produces sclerotic growth recovery lines in the long bones
• Formation of pseudarthrosis at sites of healing fractures
• Short stature

Limbs

• Olecranon apophyseal avulsion fracture (most common presenting sign)

Head, neck and spine

• Basilar invagination
• Wormian bones
• Kyphoscoliosis
• Vertebral compression fractures
• Codfish vertebrae
• Platyspondyly

Chest

• Pectus excavatum or carinatum
• Accordion ribs

Pelvis

• Protrusio acetabuli – defined as >3 mm medial deviation of the femoral head beyond the ilioischial line in males and >6 mm in females.
• Coxa vara

Diagnosis & Classification

Sillence Classification
Type	Inheritance & Gene	Features
Type I	AD. Null COL1A1 allele. Quantitative disorder in collagen.	Mildest form. Presents at preschool age (tarda). Hearing deficit in 50%. Type A and B based on tooth involvement. Blue sclera.
Type II	AD. COL1A1, COL1A2. Qualitative disorder in collagen	Lethal in perinatal period. Blue sclera.
Type III	AD. COL1A1, COL1A2. Qualitative disorder in collagen	Severe, progress and deforming. Most severe survivable form. Progressively short stature. Fractures at birth.  Normal sclera.
Type IV	AD. COL1A1, COL1A2. Qualitative disorder in collagen	Moderate severity, variable and deforming. Bowing bones and vertebral fractures. Hearing normal. Type A and B based on tooth involvement. Normal sclera.

Differential Diagnosis

• Non-accidental injury (NAI)/suspected physical abuse – Fractures tend to be asymmetric
• Osteopaenia of prematurity
• Osteomalacia
• Juvenile osteoporosis
• Hypophosphatasia
• Rickets
• Menkes Syndrome 

Management

• Type I and IV are imaged for routine fracture evaluation.