Medicine:Sclerosteosis
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] As of April 2025, inhibition of Wnt-specific acyltransferase, an enzyme coded for by the gene PORCN (nicknamed "porcupine"), has emerged under the nickname "porcupine inhibition" as a promising pharmacological treatment for severe sclerosteosis pathologies and is currently in preclinical research.[4]
Cause
Sclerosteosis is caused by mutations in the SOST gene that encodes the sclerostin protein.[5] 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
References
- ↑ 1.0 1.1 1.2 1.3 1.4 "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. doi:10.1093/hmg/10.5.537. PMID 11181578.
- ↑ "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. PMID 13539104.
- ↑ "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. doi:10.1136/jmg.39.2.91. PMID 11836356.
- ↑ Dreyer, Timothy J.; Keen, Jacob A. C.; Wells, Leah M.; Hopkinson, Mark; Orriss, Isabel R.; Holdsworth, Gill; Pitsillides, Andrew A.; Roberts, Scott J. (2025-04-07). "Porcupine inhibition is a promising pharmacological treatment for severe sclerosteosis pathologies" (in en). Bone Research 13 (1): 44. doi:10.1038/s41413-025-00406-3. ISSN 2095-6231. PMC 11973224. https://www.nature.com/articles/s41413-025-00406-3.
- ↑ "Genetics of Sost/SOST in sclerosteosis and van Buchem disease animal models". Metabolism 80: 38–47. March 2018. doi:10.1016/j.metabol.2017.10.005. PMID 29080811.
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
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