Trico-rhino-phalanga (Langer Giedion-) Syndrome ... Langel-Giedion Syndrome - Genes TRPS1, EXT1 and chromosome 8  

Syndrome Langer-Giedion is a disorder that causes bone abnormalities and facial features. People with this condition have multiple noncancerous bone tumors, which can cause pain, limitation of joint movement, and the pressure on the nerves, blood vessels, spinal cord and the tissues surrounding bone exostosis. Affected individuals also have short stature. The characteristic appearance of individuals with this disorder includes thinning hair on the scalp, a rounded nose, philtrum and a thin upper lip. Affected individuals may have some form of intellectual disability.

This process is due to mutations in the EXT1 and TRPS1 genes on chromosome 8. It was determined that the loss of functional EXT1 gene, located on the long arm of chromosome 8 (8q24.11), is responsible for multiple exostosis in people with this syndrome. This gene encodes exostosina-1 protein, which is found in cells in the Golgi, where enzymes and other proteins synthesized modified. In the Golgi apparatus, the exostosina-1 binds to exostosina-2 protein to form a complex amending heparan sulfate. The heparan sulfate is involved in the regulation of a variety of organic processes including blood clotting and angiogenesis. Also it has a role in metastasis of cancer cells. Loss TRPS1 functional gene can cause bone and facial features anomalies.

There are more than 200 mutations in the EXT1 gene causing the Langer-Giedion syndrome, due to loss of function exostosina-1 protein, preventing complex formation with exostosina-2 protein and the addition of heparán- sulfate proteins.

The TRPS1 gene on the long arm of chromosome 8 (8q24.12),   encodes a protein that regulates the activity of many other genes. This protein interacts with specific regions probably DNA and other proteins to activate or deactivate genes. Based on this function, the TRPS1 protein is a transcription factor, and intervenes in the regulation of bone and cartilage growth. Mutations in the gene TRPS1 interrupt normal bone growth, contributing to short stature, and distinctive facial features in individuals with Langer-Giedion syndrome.

The EXT1 and TRPS1 always missing or genes are mutated in affected individuals, but also other genes may be involved. The loss of additional genes in this region of chromosome 8 probably contributes to the various features of this condition.

Most cases of Langer-Giedion syndrome of not inherited. However, one of the parents of an affected individual, random events occur during the formation of eggs or sperm. These cases occur in people with no history of disease in your family. There have been very few cases where people with Langer-Giedion syndrome of inherited chromosomal mutation from a parent with the disease. Syndrome Langer-Giedion is considered an autosomal dominant condition because a copy of chromosome 8 altered in each cell is sufficient to cause the disorder.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome Langer-Giedion, by complete PCR amplification of the exons of EXT1 and TRPS1 respectively, and subsequent sequencing genes.

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).