Common variable moderate Osteogenesis Imperfecta with normal sclerae (OI type IV)

(OMIM phenotype number #166220)

Common variable moderate Osteogenesis Imperfecta with normal sclerae (OI type IV) is a moderate form of OI (see also OI type I). It is characterized by increased bone fragility, low bone mass (DEXA z-scores in the range of –3 to –5 SD), and susceptibility to bone fractures. Most fractures occur either prior to puberty or beyond middle age. Vertebral compressions in childhood and laxity of paraspinal muscles may lead to significant scoliosis. Patients with OI type IV show also moderately short stature, grayish or white sclera, and dentinogenesis imperfecta. Body proportions approach normal, although the legs are still short for the trunk and the cranium is relatively macrocephalic. With medical intervention these individuals have an essentially normal life span.

Gene

  • COL1A1 gene, 17q21.33 (OMIM gene/locus number #120150).
  • COL1A2 gene, 7q21.3 (OMIM gene/locus number #120160).
  • WNT1 gene, 12q13.12 (OMIM gene/locus number #164820).
  • CRTAP gene, 3p22.3 (OMIM gene/locus number #605497).
  • PPIB gene, 15q22.31 (OMIM gene/locus number #123841).
  • SP7 gene, 12q13.13 (OMIM gene/locus number #606633).
  • PLS3 gene, Xq23 (OMIM gene/locus number #300131).

Phenotype

Moderate form of OI, some cases indistinguishable from type III, adult hearing loss, variable phenotype, osteoporosis, bone fractures, short stature, vertebral deformity and scoliosis, triangular face, normal sclerae, hypermobility of the joints, and mild dentinogenesis imperfecta in some cases.

Images

Fig. X-rays of a patient affected by OI type IV. (A) Radiograph shows the neonatal skeletal survey. Note the gracile and poorly mineralized ribs and short femurs with bilateral midshaft fractures and flared metaphyses. (B) Radiograph of the lower extremities before rod placement at about 4 years of age. There are marked osteoporosis, thin cortices, and a healing fracture of the left femur. The long bones have undergone notable remodeling and are of a more normal overall configuration as compared to (A).

This research was originally published in J Biol Chem. Marini JC, Grange DK, Gottesman GS, et al. Osteogenesis imperfecta type IV. Detection of a point mutation in one alpha 1(I) collagen allele (COL1A1) by RNA/RNA hybrid analysis. J Biol Chem. 1989;264:11893-900. © The American Society for Biochemistry and Molecular Biology.

Other resources:

References

  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. 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.
  5. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  6. http://www.omim.org