Sclerosteosis Explained

Sclerosteosis is an autosomal recessive disorder characterized by bone overgrowth. It was first described in 1958^{[1] [2]} but given the current name in 1967.^[3] Excessive bone formation is most prominent in the skull, mandible and tubular bones.^[1] It can cause facial distortion and syndactyly.^[1] Increased intracranial pressure can cause sudden death in patients.^[1] It is a rare disorder that is most prominent in the Afrikaner population in South Africa (40 patients), but there have also been cases of American and Brazilian families.^[1]

Cause

Sclerosteosis is caused by mutations in the SOST gene that encodes the sclerostin protein.^[4] The sclerostin protein is necessary in inhibiting the Wnt signaling pathway. Wnt signalling results in increased osteoblast activity and RANKL synthesis. Sclerostin therefore increases bone formation by indirectly inhibiting RANKL synthesis and thus osteoclast activation.

See also

• Van Buchem disease

External links

• "These Superhumans Are Real and Their DNA Could Be Worth Billions", Bloomberg
• "Sclerostin Inhibition in the Management of Osteoporosis", Calcif. Tissue Int.
• "Neurosurgeons successfully implant 3D printed skull", Wired

Notes and References

1. Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, Paes-Alves AF, Hill S, Bueno M, Ramos FJ, Tacconi P, Dikkers FG, Stratakis C, Lindpaintner K, Vickery B, Foernzler D, Van Hul W . Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST) . Human Molecular Genetics . 10 . 5 . 537–43 . Mar 2001 . 11181578 . 10.1093/hmg/10.5.537 . free .
2. Truswell AS . Osteopetrosis with syndactyly; a morphological variant of Albers-Schönberg's disease . The Journal of Bone and Joint Surgery. British Volume . 40-B . 2 . 209–18 . May 1958 . 13539104 .
3. Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C, Dioszegi M, Dikkers FG, Hildering P, Willems PJ, Verheij JB, Lindpaintner K, Vickery B, Foernzler D, Van Hul W . Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease . Journal of Medical Genetics . 39 . 2 . 91–7 . Feb 2002 . 11836356 . 1735035 . 10.1136/jmg.39.2.91 .
4. Sebastian A, Loots GG . Genetics of Sost/SOST in sclerosteosis and van Buchem disease animal models . Metabolism . 80 . 38–47 . March 2018 . 29080811 . 10.1016/j.metabol.2017.10.005 . free .