(OMIM phenotype number #259420)

Osteogenesis imperfecta (OI) is a group of genetic disorders (see also OI type I), of which Progressively deforming OI type III is the most severe among survivors. OI type III is characterised by bone fragility, low bone mass and increased incidence of fractures. Other clinical signs are muscle hypotonia, joint hypermobility, triangular face, severe scoliosis, grayish sclera, dentinogenesis imperfecta and short stature. Fractures and weak bones may cause limb and spinal deformity and chronic physical disability.

Bisphosphonates are the main treatment of newborn children with severe OI type III. In most patients, surgery is necessary for high frequency of the fractures.


  • COL1A1 gene, 17q21.33 (OMIM gene/locus number +120150).
  • COL1A2 gene, 7q21.3 (OMIM gene/locus number *120160).
  • BMP1 gene, 8p21.3 (OMIM gene/locus number *112264).
  • CRTAP gene, 3p22.3 (OMIM gene/locus number *605497).
  • FKBP10 gene, 17q21.2 (OMIM gene/locus number *607063).
  • LEPRE1 gene, 1p34.2 (OMIM gene/locus number *610339).
  • PLOD2 gene, 3q24 (OMIM gene/locus number *601865).
  • PPIB gene, 15q22.31 (OMIM gene/locus number *123841).
  • SERPINF1 gene, 17p13.3 (OMIM gene/locus number *172860).
  • SERPINH1 gene, 11q13.5 (OMIM gene/locus number *600943).
  • TMEM38B gene, 9q31.2 (OMIM gene/locus number *611236).
  • WNT1 gene, 12q13.12 (OMIM gene/locus number *164820).


Severe form of OI, progressive with age, born prematurely and small for gestational age, marked impairment of linear growth, progressive deformity of long bones and spine, blue/gray or white sclerae, dentinogenesis imperfecta, severe bone dysplasia, severe osteoporosis with multiple fractures and bone deformities (more than 3 prepubertal fractures per annum), soft and shorter long bones, joint laxity, chronic bone pain, triangular face with frontal bossing, and dentinogenesis imperfecta in some cases.

Main biochemical alterations

  • (BMP1 gene mutation) Normal to slightly high ALP; in some patients: low P1CP and/or high Ur DPD/Cr.
  • (omim: #610968, FKBP10 gene mutation) High AP.
  • (omim: #259450, FKBP10 gene mutation) High Ur OHP.
  • (PLOD2 gene mutation) High Ur OHP.


Fig. X-rays of long bones and thoracic vertebrae. (A) Lower long bones of the 9-year-old girl with OI type III. The long bones are extremely osteoporotic with poor modeling and disorganized popcorn growth plates. (B) All thoracic vertebrae are severely compressed.

This research was originally published in J Biol Chem. Wang Q, Forlino A, Marini JC. Alternative splicing in COL1A1 mRNA leads to a partial null allele and two In-frame forms with structural defects in non-lethal osteogenesis imperfecta. J Biol Chem. 1996;271:28617-23. © The American Society for Biochemistry and Molecular Biology

Other resources:


  1. Van Dijk FS, Sillence DO. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A. 2014 Jun;164A(6):1470-81.
  2. Eyre DR, Weis MA. Bone collagen: new clues to its mineralization mechanism from recessive osteogenesis imperfecta. Calcif Tissue Int. 2013 Oct;93(4):338-47.
  3. Valadares ER, Carneiro TB, Santos PM, et al. What is new in genetics and osteogenesis imperfecta classification? J Pediatr (Rio J). 2014 Nov-Dec;90(6):536-41.
  4. Sinikumpu JJ, Ojaniemi M, Lehenkari P et al. Severe osteogenesis imperfecta Type-III and its challenging treatment in newborn and preschool children. A systematic review. Injury. 2015 Aug;46(8):1440-6.
  5. Marini J, Smith SM. Osteogenesis Imperfecta. Editors In: De Groot LJ, Beck-Peccoz P, Chrousos G, et al. editors. Source Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. 2015 Apr 22.
  6. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  7. http://www.omim.org