Genetics of Osteogenesis Imperfecta Clinical Presentation

Patients often have a family history of osteogenesis imperfecta (OI), but most cases are due to new mutations.

• Patients most commonly present with fractures after minor trauma.
• In severe cases, prenatal screening ultrasonography performed during the second trimester may show bowing of long bones, fractures, limb shortening, and decreased skull echogenicity. Lethal osteogenesis imperfecta cannot be diagnosed with certainty in utero.
• Patients may bruise easily.
• Patients may have repeated fractures after mild trauma. However, these fractures heal readily.
• Deafness is another feature. About 50% of patients with type I osteogenesis imperfecta have deafness by age 40 years.

Physical examination can vary depending on the severity. Degrees of severity may vary among different affected members of the same family.

• Type I - Mild forms

  • Patients have no long-bone deformity.
  • The sclera can be blue or white. Blue sclera may also occur in other disorders, such as progeria, cleidocranial dysplasia, Menkes syndrome, cutis laxa, Cheney syndrome, and pyknodysostosis.
  • Dentinogenesis imperfecta may be present.
  • Over a lifetime, numbers of fractures can range from 1-60 or more.
  • Height is usually normal in individuals with mild forms of osteogenesis imperfecta.
  • People with osteogenesis imperfecta have a high tolerance for pain. Old fractures can be discovered in infants only after radiographs are obtained for other reasons other than an assessment of osteogenesis imperfecta, and they can occur without any signs of pain.
  • Exercise tolerance and muscle strength are significantly reduced in patients with osteogenesis imperfecta, even in the mild forms.
  • Fractures are most common during infancy but may occur at any age.
  • Other possible findings include kyphoscoliosis, hearing loss (at any age),^[8] premature arcus senilis, and easy bruising.
• Type II - Extremely severe

  • Type II is often (but not always) lethal.
  • Blue sclera may be present.
  • Patients may have a small nose, micrognathia, or both.
  • All patients have in utero fractures, which may involved the skull, long bones, and/or vertebrae.
  • The ribs are beaded, and the long bones are severely deformed.
  • Causes of death include extreme fragility of the ribs, pulmonary hypoplasia, and malformations or hemorrhages of the CNS.
• Type III - Severe

  • Patients may have joint hyperlaxity, muscle weakness, chronic unremitting bone pain, and skull deformities (eg, posterior flattening) due to bone fragility during infancy.
  • Deformities of upper limbs may compromise function and mobility.
  • The presence of dentinogenesis imperfecta is independent of the severity of the osteogenesis imperfecta.
  • The sclera have variable hues.
  • In utero fractures are common.
  • Limb shortening and progressive deformities can occur.
  • Patients may have a triangular face with frontal bossing. Malocclusion is common.
  • Basilar invagination is an uncommon but potentially fatal occurrence in osteogenesis imperfecta.
  • Vertigo is common in patients with severe osteogenesis imperfecta.
  • The incidence of congenital malformations of the heart in children with osteogenesis imperfecta is probably similar to that of the healthy population.
  • Hypercalciuria may be present in about 36% of patients with osteogenesis imperfecta but does not appear to affect renal function.
  • Respiratory complications secondary to kyphoscoliosis are common in individuals with severe osteogenesis imperfecta.
  • Constipation and hernias are also common in people with osteogenesis imperfecta.
• Type IV - Undefined

  • This type of osteogenesis imperfecta is not clearly defined.
  • Whether patient have normal height or whether scleral hue defines the type has not been established in consensus.
  • Dentinogenesis imperfecta may be present. Some have suggested that this sign can be used to divide type IV osteogenesis imperfecta into subtypes a and b.
  • Fractures usually begin in infancy, but in utero fractures may occur. The long bones are usually bowed.

• Osteogenesis is an inherited disorder.
• In almost all cases, mode of inheritance in osteogenesis imperfecta is dominant or involves a new dominant mutation, regardless of the clinical form of osteogenesis imperfecta observed.
• A recessive pattern of inheritance has been demonstrated in some families from South Africa.
• Some have proposed possible germ-cell mosaicism as an explanation for cases occurring in families with healthy parents that have more than one child with osteogenesis imperfecta.
• Syndromes resembling osteogenesis imperfecta (SROI) are usually inherited in recessive fashion.