Van Buchem disease, or hyperostosis corticalis generalisata, is an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

skeletal disease which is characterised by uninhibited bone growth, especially in the

mandible In anatomy, the mandible, lower jaw or jawbone is the largest, strongest and lowest bone in the human facial skeleton. It forms the lower jaw and holds the lower tooth, teeth in place. The mandible sits beneath the maxilla. It is the only movabl ...

, skull and ribs. The disease was first described in 1955 by Prof. Franciscus Stephanus Petrus van Buchem, when describing two patients of the same family in

Urk Urk () is a municipality and a town in the Flevoland province in the central Netherlands. Urk is first mentioned in historical records dating to the 10th century, when it was still an island in the Zuiderzee, an inland sea that would become part ...

in the Netherlands. The cause, he found, was that the bone was produced faster than the body broke it down, making it much thicker as the patient got older. The first symptoms experienced by the affected were often

deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is written ...

and

paralysis Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...

of the face, caused by the growing bone pinching the

nerves A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...

. This condition can be traced to a deletion on

chromosome 17 Chromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 83 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total D ...

q. As the disease is recessive, a child will only be affected by the disease if both of the parents are carriers and the child is

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

for the

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

, meaning that they have the allele in duplicate. The gene involved is SOST, and by extension the protein involved is

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

. There have been attempts to relieve a patient suffering from van Buchem disease: "A large bilateral frontoparietal craniotomy and decompression of the

foramen magnum The foramen magnum ( la, great hole) is a large, oval-shaped opening in the occipital bone of the skull. It is one of the several oval or circular openings (foramina) in the base of the skull. The spinal cord, an extension of the medulla oblon ...

resulted in almost complete relief of his symptoms." __TOC__

Urk

There are fewer than 30 confirmed patients known to suffer from this disease; 22 of them are from the Netherlands and 14 are from Urk. Whilst previously an island in the Zuiderzee, in 1942 the land was reclaimed. However, the residents still remained a closed community, and the centuries of isolation have led to a consequence in almost exclusive intermarriage. This has increased the risk of certain hereditary disorders such as Van Buchem's and has promoted several hereditary characteristics within Urk.

References

External links

Van Buchem Disease
in the

Online Mendelian Inheritance in Man Online Mendelian Inheritance in Man (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, with a particular focus on the gene-phenotype relationship. , approximately 9,000 of the over 25,000 entries in OMIM r ...

(OMIM) Skeletal disorders {{Genetic-disorder-stub