Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Sclerosing bone dysplasia related SOST (Sclerosteosis and Van Buchem disease) (SOST sclerosing bone dysplasia-related) - Gen SOST            

Sclerosing bone dysplasia related SOST is impaired bone development characterized by hyperostosis. As a result of hyperostosis, bones throughout the body are thicker and more extensive than normal, especially the cranial bones.

Signs and symptoms derived sclerosing bone dysplasia related SOST typically include a jaw enlarged with misaligned teeth; midface hypoplasia; Proptosis eye; and a prominent forehead. Often these individuals have headaches because the increased thickness of the skull bones increases pressure on the brain. Hyperostosis seems to occur throughout life, so skeletal characteristics tend to be more pronounced over time. However, the bone overgrowth can occur only in certain areas. In addition, the abnormal growth can compress bone cranial nerves, which can result in paralysis of the facial nerve, hearing loss, vision loss, hyposmia or anosmia. Abnormal bone growth can cause potentially fatal complications if the brainstem is compressed.

There are two forms of sclerosing bone dysplasia associated with SOST: sclerosteosis and Van Buchem disease. The two forms are distinguished by the severity of their symptoms. Sclerosteosis is the most severe form of the disease. Often these individuals have sindactilia. While syndactyly is congenital skeletal features usually appear in early childhood. Sclerosteosis people may also have deformity or absence of nails. Van Buchem disease represents the milder form. People with Van Buchem disease usually are of medium height and have sindactilia or nail abnormalities. Affected individuals often have less severe compression of cranial nerve, resulting in minor neurological features. In people with Van Buchem disease, skeletal features usually appear in childhood or adolescence.

As the name suggests, sclerosing bone dysplasias related SOST is due to alterations in the gene sequence SOST (Sclerostin), located on the long arm of chromosome 17 (17q11.2), which encodes the protein sclerostin. This protein is encoded in bone osteocytes. The main function of sclerostin is inhibiting bone formation. Over time, the bone maintenance requires a balance between the formation of new bone and the resorption. Inhibition of bone formation is necessary for ensuring that the bones are the shape, size and correct density. Studies suggest that sclerostin exerts its interfering with Wnt signaling, which plays a key role in regulating bone formation effects. Moreover, sclerostin may promote apoptosis of bone cells, further inhibiting bone growth.

They have been described at least six mutations at or near the SOST gene in people with this disease. Most mutations leading to sclerosteosis cause a premature stop signal in encoding sclerostin. These mutations inhibit the synthesis of any functional protein. The most common mutation responsible for the disease in people Buchem Van Dutch ancestry is a deletion of nucleotides 52,000 in a region of SOST gene DNA. This region, called regulatory region normally controls expression of the gene. This deletion within the regulatory region reduces expression of SOST gene, leading to a deficiency of functional protein sclerostin. Deficiency or absence of sclerostin in bone cells disrupts the inhibitory effect of the protein on bone growth, causing excessive bone formation. As a result, the bones are more dense and extensive than usual, particularly the skull bones. These skeletal abnormalities are characteristic of the sclerosing bone dysplasia related SOST.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with sclerosing bone dysplasia related SOST, by complete PCR amplification of exons SOST gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).