RheumatologyTier 2Disease (DEADMAN)

Hereditary connective tissue disorders - osteogenesis imperfecta

Description

Osteogenesis imperfecta (OI) - a group of inherited connective tissue disorders, most commonly from type I collagen gene defects (COL1A1/COL1A2), causing bone fragility/recurrent fractures alongside characteristic extra-skeletal features

Most commonly autosomal dominant; severity spans a wide spectrum from mild (occasional fractures, normal lifespan) to severe/lethal perinatal forms, classified into multiple subtypes by clinical severity and, increasingly, specific genetic cause

Defective type I collagen (the major structural protein of bone matrix) impairs bone matrix quality and mineralisation, producing bones that are of near-normal or reduced density but with abnormal structural integrity, fracturing with minimal or no trauma

Recurrent fragility fractures from minimal trauma, often from childhood; blue/grey sclerae (thinned sclera allowing the underlying choroid to show through - a classic, though not universal, sign); dentinogenesis imperfecta (fragile, discoloured teeth); progressive hearing loss in some subtypes; short stature and skeletal deformity in more severe forms
Diagnosis combines clinical features, family history, and increasingly genetic testing (COL1A1/COL1A2 and other rarer causative genes) to confirm and subtype
A key differential is non-accidental injury in a child presenting with multiple fractures - recognising the OI phenotype (extra-skeletal features, family history, fracture pattern) is important for this differential, though the two are not mutually exclusive and both should be considered as appropriate

No cure - management is supportive/preventive: bisphosphonates reduce fracture frequency and bone pain in moderate-severe OI by increasing bone density, though the effect on overall bone quality/strength is more nuanced than in typical osteoporosis
Physiotherapy/rehabilitation to maximise function and mobility, orthopaedic management of fractures/deformity (including surgical rodding for recurrent long bone fractures in severe disease), and genetic counselling given the inheritance pattern

Dentinogenesis imperfecta, hearing loss, non-accidental injury (as an important differential in paediatric presentation), joint hypermobility (overlapping features with some connective tissue disorders)

OI spans an enormous severity spectrum from mild (a handful of fractures over a lifetime, normal life expectancy) to perinatally lethal - genetic subtype increasingly informs this prognostic range, though clinical severity remains the primary practical guide to management intensity

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