Osteogenesis imperfecta

Osteogenesis Imperfecta (OI) is a congenital, non-sex-linked, hereditary disorder involving connective tissues.

The hallmark feature of osteogenesis imperfecta is fragile bones that fracture easily. Osteogenesis imperfecta affects both bone quality and quantity (i.e. bone mass) ⁶.

Epidemiology

The estimated incidence is a approximately 1 in every 12,000-15,000 births ². Osteogenesis imperfecta occurs with equal frequency among males and females and across races and ethnic groups. The life span varies with the type (see osteogenesis imperfecta classification).

Clinical presentation

The clinical presentation of osteogenesis imperfecta is highly variable, ranging from a mild form with no deformity, normal stature, and few fractures to a form that is lethal during the perinatal period.

Pathology

A fundamental pathology in osteogenesis imperfecta (OI) is a disturbance in the synthesis of type I collagen, which is the predominant protein of the extracellular matrix of most tissues. In bone, this defect results in osteoporosis, thus increasing the tendency to fracture. Besides bone, type I collagen is also a major constituent of dentin, sclerae, ligaments, blood vessels, and skin ⁴.

Genetics

Osteogenesis Imperfecta is the result of a mutation in one of the two genes that carry instructions for making type 1 collagen. Mutations in the COL1A1 and COL1A2 genes are responsible for more than 90 percent of all cases.

Depending on the type, the inheritance of the disorder can be autosomal-dominant, autosomal-dominant with new mutations, or autosomal-recessive ^2,6.

Classification

The first classification of osteogenesis imperfecta was by Looser, in 1906 who divided the condition into two forms, osteogenesis imperfecta congenita (also known as Vrolik disease) and osteogenesis imperfecta tarda (also known as Ekman-Lobstein disease).

Since then newer classification systems were based on work by Sillence and colleagues in 1979, have taken into account the phenotypic features and the mode of inheritance. This has since been revised and up to eight forms of osteogenesis imperfecta have been identified.

In general, four major clinical features characterize osteogenesis imperfecta ⁵:

1. osteoporosis with abnormal bone fragility
2. blue sclera
3. dentinogenesis imperfecta
4. hearing impairment

Other features include ligamentous laxity and hypermobility of joints, short stature, and easy bruising.

Three main types are easily distinguished :

1. mild - type I
2. perinatal lethal - type II
3. progressive deforming - type III

Types IV to VIII are variable in severity and uncommon (see osteogenesis imperfecta classification for further detail).

Associations

• congenital cataracts

Radiographic features

Plain film

This is the preferred initial examination.

• head, neck & spine :
  • basilar invagination
  • wormian bones
  • kyphoscoliosis
  • vertebral compression fractures
  • codfish vertebrae
  • platyspondyly
• chest :
  • pectus excavatum or carinatum
• pelvis :
  • acetabular protrusio
• general :
  • severe osteoporosis
  • deformed, gracile (overtubulated) bones
  • cortical thinning
  • hyperplastic callus formation
  • popcorn calcification : the metaphyses and epiphyses exhibit numerous scalloped radiolucent areas with sclerotic margins ¹
  • zebra stripe sign : cyclic bisphosphonate treatment produces sclerotic growth recovery lines in the long bones
  • exuberant callus formation
  • formation of pseudoarthroses at sites of healing fractures

Pre-natal ultrasound

The pre-natal sonographic features are often useful in the type II (peri natal) and type III forms.

• may show decreased calvarial ossification
  • this may result over visualisation of fetal brain detail
  • the skull may deform / compress with transducer pressure
• may show evidence of fractures 
  • long bones may appear shortened and / or angulated as a result
  • there may be a sonographic gap along the length of a long bone 
  • rib may nave a beaded appearance
• there may be presence of polyhydramnios ⁸

CT

While showing most of the plain film feature, CT may also better demonstrate

• wormian bones
• basilar invagination
• otosclerosis ³

MRI

• can be used to assess extent of basilar invagination

Treatment and prognosis

Prognosis is very variable dependent on type ranging from being uniformly lethal from type II to a slight reduction in life expectancy for type I

Management options for non lethal types include :

• surgical correction of deformities and the prevention of fractures.
  • intramedullary rods with osteotomy are used to correct severe bowing of the long bones.
  • intramedullary rods are also recommended for children who repeatedly fracture long bones.
  • different types of rods (surgical nails) are available to address issues related to surgery, bone size, and the prospect for growth. The two major categories of rods are telescopic and non-telescopic ².
• bisphosphonates
• growth hormone therapy

Differential diagnosis

General considerations on paediatric plain films include

• juvenile osteoporosis
• Menkes syndrome (or kinky-hair syndrome)
• hypophosphatasia
• battered child syndrome (syndrome X)
• temporary brittle-bone disease
• child abuse ⁶