Multiple familial Trichoepithelioma (Multiple familial trichoepithelioma) - Gen CYLD

Multiple family trichoepithelioma is a disorder including multiple skin tumors that develop from the skin - associated structures such as hair follicles and sweat glands. People with familial multiple Trichoepithelioma develop a large number of tumors, called trichoepitheliomas, arising from hair follicles. They are generally benign tumors, but sometimes can become a type of skin neoplasia, basal cell carcinoma. Sometimes, individuals with familial multiple Trichoepithelioma also develop other types of tumors, including spiradenomas and cylindromas. The spiradenomas develop in the sweat glands. The origin of the cylindromas is not clear, having thought derived from the sweat glands, but is now thought to begin in the hair follicles. Affected individuals also have a higher risk of developing tumors in tissues other than the skin appendages, such as benign or malignant tumors of the salivary glands.

People with familial multiple Trichoepithelioma, begin to develop tumors in childhood or adolescence. Tumors occur mainly on the face, especially in the nasolabial folds, but can also appear on the neck, scalp or trunk, and can increase in size and increase in number over time. In severe cases, the tumors can affect the eyes, ears, nose, or mouth and affect 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 multiple Trichoepithelioma family are affected more severely than men.

This process is due to mutations in the gene CYLD, located on the long arm of chromosome 16 (16q12.1), which encodes a protein that helps regulate nuclear factor-kappa-B. This factor is a group of related proteins that help protect cells from apoptosis 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 necessary. By this mechanism, CYLD protein acts as a tumor suppressor, preventing cells from growing and dividing too rapidly or uncontrollably.

They have identified at least 22 mutations in the gene CYLD, in individuals with familial multiple trichoepitelioma. Individuals with familial multiple trichoepithelioma born with a mutation in one of the two copies of the gene in every cell CYLD. This mutation prevents the cell synthesizes CYLD functional protein from the altered copy of the gene. However, sufficient amount of normal protein is produced from the other copy that does not contain mutations, and regulates cell growth effectively. For tumors to develop, must be present 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. When both copies of the gene are mutated CYLD in a particular cell, the cell can not encode functional protein CYLD no. The loss of this protein allows the cell to grow and divide uncontrollably to form a tumor.

It has been considered that the familial multiple trichoepithelioma and two related disorders, familial cylindromatosis syndrome Brooke-Spiegler, also be due to gene mutations CYLD, and would be different forms of the same process. In the Brooke-Spiegler syndrome due to mutations in the gene CYLD, described at least 20 mutations. This alteration is characterized by multiple benign tumors that develop in structures associated with the skin and its annexes. People with Brooke-Spiegler syndrome can develop various types of tumors of skin appendages, including spiradenomas called, trichoepitheliomas, and cylindromas. Meanwhile, they have identified more than 30 mutations in the gene CYLD in people with familial cylindromatosis. People with this condition often develop a large number of cylindromas. As in the Brooke-Spiegler syndrome, individuals with familial cylindromatosis born with a mutated copy of the gene in every cell CYLD, and a second mutation or deletion of genetic material involving the other copy of the gene CYLD. It is unclear why mutations in the gene CYLD cause different types of skin tumors, or why tumors are generally limited to the skin in these processes.

The familial multiple trichoepithelioma 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 was not inherited for the development of skin tumors is required.

Tests in IVAMI: in IVAMI perform detection of mutations associated with familial multiple trichoepithelioma, 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).