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Nat Rev Dis Primers. 2017 Aug 18;3:17052. doi: 10.1038/nrdp.2017.52.

Osteogenesis imperfecta.

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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, Maryland 20892, USA.
Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Pavia, Italy.
Shriners Hospital for Children, Research Department, Portland, Oregon, USA.
University of Sheffield and Sheffield Children's NHS Foundation Trust, Sheffield, UK.
Department of Pathology and Medicine (Medical Genetics), University of Washington, Seattle, Washington, USA.
Ghent University Hospital, Department of Medical Genetics, Ghent, Belgium.
Shriners Hospital for Children and McGill University, Montréal, Québec, Canada.
Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Center Meidling, 1 st Med. Dept., Hanusch Hospital, Vienna, Austria.
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Department of Orthopaedic Surgery and Human Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, California, USA.
Shriners Hospital for Children, Montréal, Québec, Canada.
Children's Hospital, University of Cologne, Cologne, Germany.


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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