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Conditions

Osteogenesis imperfecta

Osteogenesis imperfecta is a group of genetic conditions that mainly affects the bones. The bones of affected individuals will fracture easily, often as a result of minor trauma or with no apparent cause.

Overview

Osteogenesis imperfecta (OI) is a heterogeneous bone fragility condition characterised by fractures, bowing of the long bones, blue sclera, anomaly of dentition and hypermobility.

Clinical features

Common clinical features include:

  • fractures (associated with minimal or no trauma; atypical fractures);
  • short stature;
  • bowing of the long bones;
  • blue sclera;
  • anomaly of dentition (dentinogenesis imperfecta);
  • hypermobility; and
  • hearing loss (post-pubertal).

Radiographic features include:

  • fractures (at various ages and stages of healing, including metaphyseal and rib fractures);
  • Wormian bones (more than 10);
  • ‘codfish’ vertebrae (the consequence of spinal compression fractures);
  • low bone mass; and
  • protrusio acetabuli (in which the hip socket pushes through the acetabulum).

Genetics

OI is heterogeneous with multiple inheritance patterns. Over 80% of cases are due to pathogenic variants in one copy of the COL1A1 or COL1A2 gene.

For many years, clinically confirmed cases of OI did not necessarily require molecular confirmation. However, given the increasing heterogeneity of OI, including multiple different inheritance types, molecular confirmation now facilitates accurate genomic counselling, and in the future it may be important for personalising treatments.

For information about testing see Presentation: Clinical suspicion of osteogenesis imperfecta.

Inheritance and genomic counselling

Genomic counselling in OI depends on the mode of inheritance.

  • Most cases (over 80%) are due to dominant pathogenic variants in COL1A1 or COL1A2, though most of these (60%) have occurred due to a new (de novo) genetic change, and the affected individual’s parents are unaffected.
  • In de novo cases, the chance of the affected individual having a child with OI is 50% (one in two), and the chance of parents having another child with OI is relatively high (3%–8% due to gonadal mosaicism, and up to 16% if somatic mosaicism is present).
    • In most rare dominant genetic diseases, the rate of gonadal mosaicism is under 1%, but in OI the rate is 3%–8%. It is not clear why, but there is a high apparent germline variant rate.
  • The second most common causal inheritance pattern in OI is autosomal recessive.
  • The least common causal inheritance pattern in OI is X-linked. Currently there are only two known causative genes associated with this inheritance pattern: PLS3 and MBTPS2.

Management

Management of children and adults with OI is complex and should be delivered via a multidisciplinary team. Supportive, medical and surgical therapies can be utilised, focusing on fracture prevention and treatment, pain control and management of other complications related to dentition and hearing.

Resources

For clinicians

References:

For patients

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  • Last reviewed: 04/05/2023
  • Next review due: 04/05/2025
  • Authors: Dr Ataf Sabir
  • Reviewers: Dr Danielle Bogue, Dr Amy Frost, Dr Emile Hendriks