: 491–492  OI type II is often diagnosed by ultrasound during pregnancy, where already multiple fractures and other characteristic features may be visible. Relative to control, OI cortical bone shows increased porosity, canal diameter, and connectivity in micro-computed tomography. OI can also be detected before birth by using an in vitro genetic testing technique such as amniocentresis. Genetic testing
In order to determine whether osteogenesis imperfecta is present, genetic sequencing of the most common problematic genes, COL1A1, COL1A2, and IFITM5, may be done; if no mutation is found yet OI is still suspected, the other 10+ genes known to cause OI may be tested. Duplication and deletion testing is also suggested to parents who suspect their child has OI. The presence of frameshift mutations caused by duplications and deletions is generally the cause of increased severity of disease. Differential diagnosis
An important differential diagnosis of OI is child abuse, as both may present to a clinician with multiple fractures in various stages of healing. : 1514  Differentiating them can be difficult, especially when no other characteristic features of OI are present. : 391  This can become an issue in court; in the United States, several child abuse cases were resolved with a finding that osteogenesis imperfecta was the true cause of a childs fractures, leading to lawsuits seeking redress such as Alice Velasquez, et al. v. United States. : 391 Other differential diagnoses include rickets and osteomalacia, both caused by malnutrition, as well as rare skeletal syndromes such as Bruck syndrome, hypophosphatasia, geroderma osteodysplasticum, and Ehlers–Danlos syndrome.
OI has high genetic heterogeneity, that is, many different genetic mutations lead to the same or similar sets of observable symptoms (phenotypes).The main causes for developing the disorder are a result of mutations in the COL1A1 and/or COL1A2 genes which are jointly responsible for the production of collagen type I. Approximately 90% of people with OI are heterozygous for mutations in either the COL1A1 or COL1A2 genes. There are several biological factors that are results of the dominant form of OI. These factors include: intracellular stress; abnormal tissue mineralization; abnormal cell to cell interactions; abnormal cell-matrix interactions; a compromised cell matrix structure; and, abnormal interaction between non-collagenous proteins and collagen.Previous research lead to the belief that OI was an autosomal dominant disorder with few other variations in genomes. However, with the lowering of the cost of DNA sequencing in the wake of 2003s Human Genome Project, autosomal recessive forms of the disorder have been identified. Recessive forms of OI relate heavily to defects in the collagen chaperones responsible for production of procollagen and the assembly of the related proteins. Examples of collagen chaperones that are defective in patients with recessive forms of OI include chaperone HSP47 (Cole-Carpenter syndrome) and FKBP65. Mutations in these chaperones result in an improper folding pattern in the collagen 1 proteins which causes the recessive form of the disorder. There are three significant types of OI that are a result of mutations in the collagen prolyl 3-hydroxylation complex (components CRTAP, P3H1, and CyPB).