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Osteogenesis imperfecta

Nature Reviews Disease Primers volume 3, Article number: 17052 (2017) Cite this article

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Abstract

Skeletal deformity and bone fragility are the hallmarks of the brittle bone dysplasia osteogenesis imperfecta. The diagnosis of osteogenesis imperfecta usually depends on family history and clinical presentation characterized by a fracture (or fractures) during the prenatal period, at birth or in early childhood; genetic tests can confirm diagnosis. Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure. In the past decade, (mostly) recessive, dominant and X-linked defects in a wide variety of genes encoding proteins involved in type I collagen synthesis, processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells have been shown to cause osteogenesis imperfecta. The large number of causative genes has complicated the classic classification of the disease, and although a new genetic classification system is widely used, it is still debated. Phenotypic manifestations in many organs, in addition to bone, are reported, such as abnormalities in the cardiovascular and pulmonary systems, skin fragility, muscle weakness, hearing loss and dentinogenesis imperfecta. Management involves surgical and medical treatment of skeletal abnormalities, and treatment of other complications. More innovative approaches based on gene and cell therapy, and signalling pathway alterations, are under investigation.

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Figure 1: Clinical features associated with osteogenesis imperfecta.
Figure 2: Structure of collagen.
Figure 3: Type I collagen synthesis and processing.
Figure 4: Defects in bone formation and mineralization in osteogenesis imperfecta.
Figure 5: Prenatal screening for osteogenesis imperfecta.
Figure 6: Lower extremity surgery in patients with osteogenesis imperfecta.

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Acknowledgements

The authors thank M. Balasubramanian (Department of Oncology & Metabolism, University of Sheffield, Sheffield Children's NHS Foundation, UK) for providing the images shown in Figure 1.

Author information

Authors and Affiliations

  1. Section on Heritable Disorders of Bone and Extracellular Matrix, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Building 49, Rm 5A42, 9000 Rockville Pike, Bethesda, 20892, Maryland, USA

    Joan C. Marini

  2. Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Pavia, Italy

    Antonella Forlino

  3. Research Department, Shriners Hospital for Children, Portland, Oregon, USA

    Hans Peter Bächinger

  4. University of Sheffield and Sheffield Children's NHS Foundation Trust, Sheffield, UK

    Nick J. Bishop

  5. Department of Pathology and Medicine (Medical Genetics), University of Washington, Seattle, Washington, USA

    Peter H. Byers

  6. Department of Medical Genetics, Ghent University Hospital, Ghent, Belgium

    Anne De Paepe

  7. Shriners Hospital for Children and McGill University, Montréal, Québec, Canada

    Francois Fassier

  8. Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, 1 st Med. Dept., Hanusch Hospital, Vienna, Austria

    Nadja Fratzl-Zelman

  9. Department of Orthopaedic Surgery, Orthopaedic Research Laboratories, University of Michigan, Ann Arbor, Michigan, USA

    Kenneth M. Kozloff

  10. Department of Orthopaedic Surgery and Human Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, California, USA

    Deborah Krakow

  11. Shriners Hospital for Children, Montréal, Québec, Canada

    Kathleen Montpetit

  12. Children's Hospital, University of Cologne, Cologne, Germany

    Oliver Semler

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  1. Joan C. Marini
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Contributions

Introduction (J.C.M.); Epidemiology (P.H.B.); Mechanisms/pathophysiology (H.P.B., A.F., O.S., A.D.P., N.F.-Z., P.H.B. and J.C.M.); Diagnosis, screening and prevention (P.H.B.); Management (K.M., D.K., F.F., N.J.B. and J.C.M.); Quality of life (K.M.); Outlook (O.S., K.M.K. and A.F.); Overview of Primer (A.F. and J.C.M.).

Corresponding author

Correspondence to Joan C. Marini.

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Competing interests

K.M.K. received support from Amgen (sclerostin antibody) and Mereo BioPharma (grant; sclerostin antibody) for research studies. N.J.B. received honoraria from Internis and Alexion, consultation fees (paid to the University) from Alexion, Ultragenyx, Mereo and Amgen, and research grants (paid to Sheffield Childrens NHS Foundation) from Amgen, Alexion and Merck. F.F. received royalties from PegaMedical. All other authors declare no competing interest.

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Marini, J., Forlino, A., Bächinger, H. et al. Osteogenesis imperfecta. Nat Rev Dis Primers 3, 17052 (2017). https://doi.org/10.1038/nrdp.2017.52

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  • DOI: https://doi.org/10.1038/nrdp.2017.52

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