Sclerosteosis 2, autosomal dominant/recessive (SOST2)

(OMIM #614305)

Sclerosteosis 2, autosomal dominant/recessive, is a sclerosing bone dysplasia caused by heterozygous or homozygous mutation in the Low density lipoprotein receptor related protein 4 (LRP4) gene (see also VBD). It has been described that the interaction of sclerostin with LRP4 is required to mediate the inhibitory function of sclerostin on bone formation (see also SOST1).

Gene

LRP4 gene, 11p11.2 (OMIM gene/locus number *604270)

Phenotype

Syndactyly/brachyphalangy with nail dysplasia, increased stature, increased head circumference, facial asymmetry due to facial nerve palsy, frontal bossing, prognathism, hearing loss, hypertelorism, wide and dense clavicles-ribs, sclerotic calvarium, enlarged and sclerotic mandible, sclerotic vertebral end plates and pedicles, sclerotic pelvic bones, cortical hyperostosis of long bones, radial deviation of distal phalanx, facial nerve palsy, and spastic-ataxic tetraparesis.

Images

Fig. (a)

Sclerosteosis 2

Fig. (b)

Sclerosteosis 2

Fig. (c) 

Sclerosteosis 2

Fig. (a) Radiographs of the hands show modeling defect of the metacarpal bones and complex fusion anomaly of the individual bones of the hands. (b) Radiograph of the skull (lateral view) shows extensive sclerosis of the calvaria, maxilla, mandible, and cervical spine. (c) Radiograph of the left lower shows thickening of the cortical bone of the diaphysis of the tibia with extension into the proximal metaphysis.

This research was originally published in J Biol Chem. Leupin O, Piters E, Halleux C, et al. Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem. 2011; 286:19489-500. © The American Society for Biochemistry and Molecular Biology.

 

References
  1. Hamersma H, Gardner J, Beighton P. The natural history of sclerosteosis. Clin Genet. 2003 Mar;63(3):192-7.
  2. Leupin O, Piters E, Halleux C, et al. Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem. 2011 Jun 3;286(22):19489-500.
  3. Beighton P, Davidson J, Durr L, Hamersma H. Sclerosteosis - an autosomal recessive disorder. Clin Genet. 1977 Jan;11(1):1-7.
  4. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  5. http://www.omim.org