Sclerosteosis is an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

disorder characterized by bone overgrowth. It was first described in 1958 but given the current name in 1967. Excessive bone formation is most prominent in the

skull The skull, or cranium, is typically a bony enclosure around the brain of a vertebrate. In some fish, and amphibians, the skull is of cartilage. The skull is at the head end of the vertebrate. In the human, the skull comprises two prominent ...

mandible In jawed vertebrates, the mandible (from the Latin ''mandibula'', 'for chewing'), lower jaw, or jawbone is a bone that makes up the lowerand typically more mobilecomponent of the mouth (the upper jaw being known as the maxilla). The jawbone i ...

and tubular bones. It can cause facial distortion and

syndactyly Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, but is an unusual condition in humans. The term is . Classification Syndactyly can be simple or complex. * In simple syndactyly, adja ...

. Increased intracranial pressure can cause sudden death in patients. It is a rare disorder that is most prominent in the

Afrikaner Afrikaners () are a Southern African ethnic group descended from predominantly Dutch settlers who first arrived at the Cape of Good Hope in 1652.Entry: Cape Colony. ''Encyclopædia Britannica Volume 4 Part 2: Brain to Casting''. Encyclopæd ...

population in

South Africa South Africa, officially the Republic of South Africa (RSA), is the Southern Africa, southernmost country in Africa. Its Provinces of South Africa, nine provinces are bounded to the south by of coastline that stretches along the Atlantic O ...

(40 patients), but there have also been cases of American and Brazilian families.

Cause

Sclerosteosis is caused by mutations in the SOST gene that encodes the

sclerostin Sclerostin is a protein that in humans is encoded by the ''SOST'' gene. It is a secreted glycoprotein with a C-terminal cysteine knot-like (CTCK) domain and sequence similarity to the DAN (differential screening-selected gene aberrative in neu ...

protein. The sclerostin protein is necessary in inhibiting the

Wnt signaling pathway In cellular biology, the Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt, pronounced "wint", is a portmanteau created from the ...

. Wnt signalling results in increased osteoblast activity and

RANKL Receptor activator of nuclear factor kappa- ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiat ...

synthesis. Sclerostin therefore increases

bone formation Ossification (also called osteogenesis or bone mineralization) in bone remodeling is the process of laying down new bone material by cells named osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in th ...

by indirectly inhibiting RANKL synthesis and thus

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...

activation.

References

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''
{{Authority control Genetic diseases and disorders Rare diseases Skeletal disorders

Cause

See also

References

External links