Nondeforming, with blue sclerae (OI type I)

(OMIM phenotype number #166200)

Osteogenesis imperfecta (OI), also known as brittle bone disease, is a genetically determined bone disorder in which either defective or insufficient quantities of collagen molecules are produced. OI includes a group of clinically and genetically heterogeneous disorders characterized by high risk of bone fractures, with variable degree of severity and presumed or proven defects in collagen type 1 biosynthesis. Common clinical signs are: increased bone fractures, and secondary features such as short stature, blue sclerae, dentinogenesis imperfecta and hearing loss may also exist in affected individuals. The incidence of the different types of OI is approximately 1/15.000-20.000 births and most cases are due to autosomal dominant inheritance with mutations in collagen, type 1 alpha-1, type 1 alpha-2 (COL1A1 or COL1A2) genes, which encode the alpha 1 and alpha 2 chains of type 1 collagen. Mutations in COL1A1 and COL1A2 genes altering the structure or the amount of type 1 collagen, result in a skeletal phenotype that ranges from subclinical to lethal. Furthermore, there are several mutant noncollagen genes causing the 5–10% of recessive cases, such as CRTAP, LEPRE1, PPIB, PLOD2, FKBP10, SERPIN H1, SERPIN F1, BMP1, and IFITM5 genes. All types of OI cause fragile bone, which can include overmineralization or under-mineralization defects as well as abnormal collagen post-translational modifications.

The therapeutic management of OI needs various medical specialists (endocrinology, orthopedics, physiotherapy..). Medical therapies recommended include: bisphosphonates, potent antiresorptive drugs, for severe forms of OI, and supplementations of vitamin D and calcium. In case of bone and spinal deformities, and long bone fractures can be necessary surgical management. At last, it is recommendable physiotherapy in order to improve mobility and reduce the risk of fractures.


COL1A1 gene, 17q21.33 (OMIM gene/locus number +120150).

COL1A2 gene, 7q21.3 (OMIM gene/locus number *120160).


Mildest form of OI, due to 50 % reduction of the amount of collagen type I; blue sclerae, joint hyperextensibility, normal tooth (OI type IA, with a reduction in the amount of normal collagen) or dentinogenesis imperfecta (OI type IB, with abnormal collagen), hearing loss (onset usually around 20 years), mitral valve prolapse, thin skin, increased fracture rate throughout childhood (ensues when child begins to walk, decreases after puberty, then increases after menopause and in men aged 60–80 years), and biconcave flattened vertebrae.

Main biochemical alterations

No specific alterations in bone markers (low sclerostin, low PINP and PICP have been reported).

Other resources:


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