osteogenesis imperfecta; osteopsathyrosis; fragilitas ossium; Lobstein's disease (OI)

Introduction

Inherited disorder characterized by osteopenia & brittle bones.

Classification

• type 1, mildest form, autosomal dominant
• type 2, lethal in utero or shortly after birth
• type 3, tends to become more severe with age
• type 4, bone fragility variable, autosomal dominant

Epidemiology

• most prevalent heritable disorder of connective tissue

Pathology

• generalized osteopenia
• aortic incompetence

Genetics

• most patients have defects in 1 of the 2 alleles for type-1 collagen alpha chain (COLA1, COLA2)
• contiguous gene deletion involving COL1A1 or COLA2 may complicate phenotypic expression

Clinical manifestations

• musculoskeletal manifestations
  • bone fractures with little pain
  • skeletal defomities: skull, trunk, limbs
  • short stature
  • hypermobility of joints
• teeth may be normal, discolored or grossly abnormal (dentinogenesis imperfecta)
• ocular manifestations
  • exophthalmos
  • blue sclerae (characteristic but not specific)
• hearing loss
  • generally begins in 2nd decade of life
  • 90% of patients over age 30
  • conductive, sensorineural or mixed
  • middle ear bony & cartilagenous deformities
• progressive neurological symptoms may result from basilar compression & communicating hydrocephalus
• younger adults with unexplained low bone density & fragility fractures may have a milder form of osteogenesis imperfecta

* cognitive impairment, delay in speech development, & self-mutilation are not typically associated

Laboratory

• genetic testing

Radiology

• hypoplastic bone
• fracture deformities

Management

• treatment is ineffective
• severely affected children should be provided with
  • physical therapy,
  • surgical management of fractures & skeletal deformities
  • vocational education
• surgical replacement of stapes for hearing loss
• aggressive treatment pneumonia & cor pulmonale
• growth hormone may increase growth in children
• bisphosphorates have been used to prevent bone loss
  • no controlled studies
• audiology & dental evaluations
• patient education
  • an appropriate amount of exercise may prevent bone loss due to inactivity
  • counseling & emotional support
    • preterm genetic counseling
  • prenatal diagnosis
    • prenatal ultrasonography will detect severely affected fetuses at 16 weeks
    • synthesis of abnormal pro-alpha collagen chains on chorionic villa biopsies at 8-12 weeks of gestation
• prognosis
  • many patients live productive lives despite severe deformities
  • risk of fractures decreases after puberty
  • risk of fractures in women increases during pregnancy & after menopause

More general terms

• developmental bone disorder
• genetic disease of bone/skeletal system
• connective tissue disease; soft tissue disease

More specific terms

• Bruck syndrome; osteogenesis imperfecta with congenital joint contractures
• gnathodiaphyseal dysplasia; osteogenesis imperfecta with unusual skeletal lesions; gnathodiaphyseal sclerosis
• osteogenesis imperfecta type I; osteogenesis imperfecta tarda
• osteogenesis imperfecta type II; osteogenesis imperfecta congenita, neonatal lethal form
• osteogenesis imperfecta type III
• osteogenesis imperfecta type IV with normal sclera
• osteogenesis imperfecta type X (type 10)

Patient information

osteogenesis imperfecta patient information