Klippel-Trenaunay Syndrome ... (Klippel-Trenaunay syndrome) - Gen PIK3CA

Klippel-Trenaunay is a process that affects the development of blood vessels, soft tissues such as skin and muscle, and bone. This process has three characteristics: red birth mark known as "port wine stain" abnormal overgrowth of soft tissue and bone, and malformation of blood vessels.

Most people with Klippel-Trenaunay syndrome are born with a red spot known as port - wine stain. This type of birthmark is due to inflammation of small blood vessels near the skin surface. These spots are generally flat and may vary from pale pink to dark brown. In affected individuals, the port wine stain usually covers part of a limb. With age, the affected area may become lighter or darker. Sometimes they develop in port wine stains small red blisters that open and bleed easily.

This syndrome is also associated with an overgrowth of bone and soft tissue, which usually begins in childhood. Usually, this abnormal growth to a member is limited, most often a leg. However, overgrowth can also affect the arms or, rarely, the torso. The abnormal growth can cause pain, heaviness and reduced movement in the affected area. If growth generates longer than the other leg, it can also cause problems with walking.

Malformations of the veins are the third important feature of this syndrome. These abnormalities include varicose veins that usually appear on the sides of the thighs and calves. The deep veins of the extremities may also be abnormal in people with Klippel-Trenaunay syndrome. Malformations of the deep veins increase the risk of deep vein thrombosis (DVT). If a thrombus dislodges the blood stream and lodge in the lungs, may cause pulmonary embolism (PE). Other complications of Klippel-Trenaunay syndrome may include cellulitis, lymphedema and internal bleeding of abnormal blood vessels. Less often, Klippel-Trenaunay is associated with syndactyly or polydactyl.

This may be due to mutations in PIK3CA gene (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), located on the long arm of chromosome 3 (3q26.3), encoding p110 protein, a subunit enzyme phosphatidylinositol 3-kinase (PI3K). The p110 catalytic subunit protein is because performing the action of PI3K, while the other subunit, encoded by a different gene, regulates the activity of the enzyme. Like other kinases, PI3K add a phosphate group to other proteins through phosphorylation. PI3K plays a role in chemical signaling within cells. PI3K signaling is important for many cellular activities, including growth and proliferation, cell migration, encoding new proteins, transport materials within cells, and cell survival. These functions are important for the development of tissues throughout the body, including the brain and blood vessels. It is believed that PI3K signaling may be involved in the regulation of various hormones and may play a role in the maturation of adipocytes.

It has identified at least five mutations in the PIK3CA gene in individuals with Klippel-Trenaunay syndrome. Mutations in PIK3CA gene associated with Klippel-Trenaunay consist of amino acid changes in the protein p110. These changes result in the synthesis of an altered subunit p110 makes PI3K be abnormally active. The altered enzyme triggers a chemical signaling unregulated in cells, allowing the cells to grow and divide continuously. Increased cell proliferation causes abnormal bone growth, soft tissue and blood vessels. Despite the involvement of PIK3CA gene mutations in cancer and excessive cell growth due to changes in this gene, individuals with Klippel-Trenaunay syndrome do not appear to have an elevated risk of developing cancer.

Klippel-Trenaunay is one of several Overgrowth syndromes including Syndrome megalencephaly capillary malformation, which is due to mutations in PIK3CA gene. Together, these processes are known as the spectrum of overgrowths related PIK3CA- (PROS). Because not all people with this syndrome have a mutation in PIK3CA gene, it is possible that mutations in other genes unidentified may also be related to the development of this disease.

Klippel-Trenaunay is almost always sporadic, meaning that occurs in people with no history of disease in your family. Studies suggest that the process may be due to genetic somatic mutations are not inherited. These genetic changes probably occur very early in development and are present only in certain cells. Somatic mutations could explain why the signs and symptoms of Klippel-Trenaunay syndrome are usually limited to specific areas of the body. As the cells continue to divide during development, cells derived from the first abnormal cell have the mutation, and other cells. This mixture of cells with and without a genetic mutation known as mosaicism.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with Klippel-Trenaunay, by complete PCR amplification of the PIK3CA gene exons and subsequent sequencing.

Recommended samples: biopsy of the affected tissues.