Shprintzen-Goldberg syndrome ... (Shprintzen-Goldberg syndrome) - Genes SKI and FBN1  

The Shprintzen-Goldberg syndrome is a disorder that affects many parts of the body. Affected individuals have a combination of distinctive facial features and skeletal and neurological abnormalities.

A common feature in those affected is craniosynostosis, which prevents the skull grow normally. Affected individuals may also have distinctive facial features, including a long, narrow head, hypertelorism, exophthalmos, palpebral fissures downward sloping, high, narrow palate, micrognathia and low - set ears that rotate back. It is often said that people with Shprintzen-Goldberg syndrome have Marfanoid habit, because their bodies resemble those of people with Marfan syndrome. For example, they may have arachnodactyly, unusually long limbs, pectus excavatum or pectus carinatum and scoliosis. People with Shprintzen-Goldberg syndrome may have other skeletal abnormalities such as camptodactilia and hypermobility. Other signs and symptoms may include developmental delay, intellectual disability, heart or brain abnormalities, hypotonia, umbilical hernia or inguinal hernia.

The Shprintzen-Goldberg syndrome have signs similar to those of Marfan syndrome and Loeys-Dietz syndrome symptoms. However, it is more likely to occur in the intellectual disability Shprintzen-Goldberg syndrome compared to the other two entities. In addition, cardiac abnormalities are more frequent and generally more serious in Marfan syndrome and in Loeys-Dietz syndrome.

Syndrome Shprintzen-Goldberg is frequently due mutations in the gene SKI (SKI proto-oncogene), located on the short arm of chromosome 1 (1p36.33). This gene encodes a protein that regulates the signaling pathway of transforming growth factor beta (TGF-?). TGF-? via the regulating many processes, including growth, proliferation, differentiation, motility and apoptosis. By binding to certain proteins in the pathway, the protein blocks SKI TGF-?. The SKI protein is found in many cell types throughout the body and appears to play a role in the development of many tissues, including the skull, other bones, skin and brain.

They have identified at least 10 mutations in the gene SKI in people with Shprintzen-Goldberg syndrome. Most of these mutations change the amino acids in protein SKI. It is believed that the altered protein is unable to bind proteins in the TGF-? pathway and block signaling. Excess TGF-? alters the regulation of gene activity and is likely to interrupt the development of many body systems, including bones and brain, resulting in the wide range of signs and symptoms of the syndrome Goldberg Shprintzen-.

Not all cases of Shprintzen-Goldberg syndrome are caused by mutations in the gene SKI. It is believed that mutations in other genes, such as the gene fibrillin-1 (FBN1), may be involved in the development of this process. In some cases, the genetic cause is unknown. FBN1 gene, located on the long arm of chromosome 15 (15q21.1), encodes fibrillin-1, an extracellular glycoprotein widely distributed that polymerizes to form myofibers, both elastic fabrics and nonelastic. The microfibrils are elastic fibers, allowing the skin, ligaments and blood vessels stretch. The microfibrils also provide more rigid support to tissues such as bone and tissues supporting the nerves, muscles and the (crystalline) lens. The microfibrils store a protein called transforming growth factor beta (TGF-?) a critical growth factor. TGF-? affects the development, helping to control growth, division, differentiation, motility and apoptosis.

Syndrome Shprintzen-Goldberg is inherited in an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease. This disease is almost always due to new genetic and occurs in people with no history of disease in your family mutations. Rarely, people with Shprintzen-Goldberg syndrome inherit the altered gene of an affected parent has a unique genetic that mutation in their sperm or eggs. When a mutation is present only in reproductive cells, known as germline mosaicism.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with Shprintzen-Goldberg syndrome, by complete PCR amplification of the exons of the SKI and FBN1, 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).