Diagnosis is often based on symptoms and may be confirmed by collagen biopsy or DNA sequencing. As of September 2021, 19 different genes are known to cause the 21 documented genetically defined types of OI, many of which are extremely rare and have only been documented in a few individuals.
![osteogenesis imperfecta type 3 osteogenesis imperfecta type 3](https://img.haikudeck.com/mi/3ba41a5248adf24cfd1a8462a2db7771.jpeg)
There are four clinically defined types: type I, the least severe type IV, moderately severe type III, severe and progressively deforming and type II, perinatally lethal. These mutations may be inherited from a person's parents in an autosomal dominant manner but may also occur spontaneously ( de novo). : 1513 In more than 90% of cases, OI occurs due to mutations in the COL1A1 or COL1A2 genes. The underlying mechanism is usually a problem with connective tissue due to a lack of, or poorly formed, type I collagen. Potentially life-threatening complications, all of which become more common in more severe OI, include: tearing ( dissection) of the major arteries, such as the aorta : 333 pulmonary valve insufficiency secondary to distortion of the ribcage : 335–341 and basilar invagination.
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: 1512 Symptoms found in various types of OI include whites of the eye (sclerae) that are blue instead, short stature, loose joints, hearing loss, breathing problems and problems with the teeth ( dentinogenesis imperfecta). : 85 The range of symptoms-on the skeleton as well as on the body's other organs-may be mild to severe. Osteogenesis imperfecta ( IPA: / ˌ ɒ s t i oʊ ˈ dʒ ɛ n ə s ɪ s ˌ ɪ m p ɜːr ˈ f ɛ k t ə/ OI), colloquially known as brittle bone disease, is a group of genetic disorders that all result in bones that break easily. Subject's BMD Z-score was -4.1 according to results of a dual-energy X-ray absorptiometry (DXA) scan also done in 2018. The unavoidably low contrast in the film is due to a combination of subject's obesity and low bone mineral density (BMD).
![osteogenesis imperfecta type 3 osteogenesis imperfecta type 3](https://d3i71xaburhd42.cloudfront.net/9e16b0bbb1b6d6c90326ca3c3f994a9d87b76499/3-Figure1-1.png)
Severe scoliosis, as well as kyphosis, are also evident. Malunions are evident as the humerus and femur were broken in adolescence but orthopedic care did not follow. Due to childhood neglect and poverty, subject never received surgery to implant intramedullary rods. Genetic diagnosis in 2018 identified a previously uncatalogued pathogenic variant in the gene which encodes proα2(I) chains of type I procollagen, COL1A2, at exon 19, substitution c.974 G> A. Four X-rays of a 24-year-old American man, who had suffered more than one hundred bone fractures in his lifetime, and received a childhood clinical diagnosis of type IV–B OI.