Cylindromatosis familiar syndrome ... (Familial cylindromatosis) - Gen CYLD

Familial cylindromatosis is a disorder involving multiple skin tumors that develop from structures associated with skin (skin tags), such as hair follicles and sweat glands. People with familial cylindromatosis often develop a large number of tumors called cylindromas. While previously it thought that cylindromas derived from the sweat glands, it is now thought to arise from hair follicles.

Individuals with familial cylindromatosis sometimes develop other types of tumors, including growths called spiradenomas and trichoepitheliomas. The spiradenomas begin to sweat glands and trichoepithelioma arising from hair follicles. Tumors associated with familial cylindromatosis are generally benign, but sometimes can become malignant. Affected individuals also have increased risk of developing tumors other than skin appendages, particularly benign or malignant salivary gland tumor tissues. Tumors begin to develop in adolescence or early adulthood, and are more often in regions with hair, with approximately 90% of cases in the head and neck, growing and increasing in number with the weather.

In people with severe disease, multiple tumors on the scalp can join one of leading large, with turban - like growth. The large growths often develop open sores and are prone to infections. Tumors can also occur in the eye region, ears, nose or mouth, affecting vision, hearing, or other functions. The growths can cause disfigurement and can contribute to depression or other psychological problems. For reasons that are not clear, women with familial cylindromatosis are affected more than men.

Familial cylindromatosis occurs as a result of mutations in the gene CYLD, located on the long arm of chromosome 16 (16q12.1). This gene encodes a protein that helps regulate nuclear factor-kappa-B. The nuclear factor kappa-B, is a group of related proteins that help protect cells from self - destruction in response to certain signals. In regulating the action of nuclear factor kappa-B, the CYLD protein allows cells to respond appropriately to the signals to self - destruct when appropriate, for example, when cells become abnormal. By this mechanism, CYLD protein acts as a tumor suppressor, which means that helps prevent cells from growing and dividing too rapidly or uncontrollably.

They have identified more than 30 mutations in the gene CYLD in individuals with familial cylindromatosis. Individuals with familial cylindromatosis born with a mutation in one of the two copies of the gene in every cell CYLD. This mutation prevents cell CYLD synthesize a functional protein from the altered copy of the gene. However, often sufficient with the protein coded from the other normal copy of the gene to regulate cell growth effectively. For tumors to develop, a second mutation, or deletion of genetic material, in the other copy of the gene CYLD in certain cells during the life of a person should occur.

The loss of this protein allows the cell to grow and divide uncontrollably to form a tumor. In people with familial cylindromatosis, CYLD the second mutation occurs in many cells during the life of the person affected. CYLD protein loss in these cells leads to growth of tumors of skin appendages.

Some researchers believe that family cylindromatosis and two related disorders called familial multiple tricoepithelioma Brooke-Spiegler and which are also caused by gene mutations CYLD syndrome appear to be different forms of the same pathology. It is unclear why mutations in the gene CYLD cause different patterns of tumors of skin appendages in each of these conditions, or why tumors are generally limited to the skin in these processes.

Familial cylindromatosis has an autosomal dominant inheritance, which means that a copy of the altered gene in each cell increases the risk of developing this condition. However, a second mutation, not inherited for the development of tumors faneras in this alteration is required.

Tests in IVAMI: in IVAMI perform detection of mutations associated with familial cylindromatosis syndrome, by complete PCR amplification of the exons of the gene CYLD, 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).