Osteogenesis imperfecta with calcification in interosseous membranes and/or hypertrophic callus (OI type V)

(OMIM phenotype number #610967)

Osteogenesis imperfecta with calcification in interosseous membranes and/or hypertrophic callus (OI type V) is a moderate form of Osteogenesis Imperfecta (see also OI type I). It is a genetic disorder characterized by increased bone fragility, low bone mass and susceptibility to bone fractures with variable severity. Clinical findings of OI type V include mild to moderate short stature, dislocation of the radial head, mineralized interosseous membranes, white sclera and no dentinogenesis imperfecta. Patients affected by OI type V can have hypertrophic callus, dense metaphyseal bands and/or ossification of the interosseus membranes of the forearm, causing severely limited pronation and supination. Recently, it was found that cases of OI type V are caused by the same recurring defect in the IFITM5 gene that encodes the BRIL (Bone-restricted IFITM-like) protein, a known osteoblast marker (highly expressed in mineralizing osteoblasts).

Gene

IFITM5 gene, 11p15.5 (OMIM gene/locus number #614757).

Phenotype

Moderate-severe OI form, similar to type IV, but without dentinogenesis imperfecta and blue sclerae, calcification of intraosseus membranes in the forearm and hyperplastic callus formation, metaphyseal bands adjacent to growth plate (distal femora, proximal tibia, distal radii), and histological mesh-like or irregular bone pattern.

Main biochemical alterations:

High ALP, and high NTX.

Images

a b c d

Fig. Two patients affected by OI type V (a) Radiograph of the femur shows a thickening of the cortical bone on the medial side (arrows) and a hyperplastic callus at the distal part of the thigh (asterisks). (b) Radiograph of the lateral spine of proband 2 with signs of vertebral fractures and wedge-shaped and biconcave deformities (arrows). (c) Radiograph of the right thigh of proband 1 at the age of 2.6 years, showing a hyperplastic callus. At the distal end of the femur, a metaphyseal band (arrow), which is a typical sign of OI type V, is visible. As a result of dislocation of the bone after a fracture, a surgical treatment involving the insertion of two rods is necessary. (d) Photograph documenting the swelling of the right thigh. 

Reproduced from Am J Hum Genet, Vol 91, Semler O, Garbes L, Keupp K, et al. A mutation in the 5'-UTR of IFITM5 creates an in-frame start codon and causes autosomal-dominant osteogenesis imperfecta type V with hyperplastic callus, Pages 349-57, Copyright 2012, with permission from Elsevier.


Other resources:

http://www.oif.org/

http://www.oife.org/

http://www.oife.org/index.php/EN/other-oi-organisations

http://www.brittlebone.org/

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