Multiple familial trichoepithelioma

Multiple familial trichoepithelioma is a rare genetic condition characterized by the development of numerous noncancerous skin tumors arising from hair follicles, typically beginning in childhood or adolescence.

Overview

Multiple familial trichoepithelioma is a condition involving multiple skin tumors that develop from structures associated with the skin (skin appendages), such as hair follicles and sweat glands. People with multiple familial trichoepithelioma typically develop large numbers of smooth, round tumors called trichoepitheliomas, which arise from hair follicles. Trichoepitheliomas are generally noncancerous (benign) but occasionally develop into a type of skin cancer.

Individuals with multiple familial trichoepithelioma occasionally also develop other types of tumors, including growths called spiradenomas and cylindromas. Spiradenomas develop in sweat glands. The origin of cylindromas has been unclear; while previously thought to derive from sweat glands, they are now generally believed to begin in hair follicles. Affected individuals are also at increased risk of developing tumors in tissues other than skin appendages, particularly benign or malignant tumors of the salivary glands.

Symptoms and Progression

People with multiple familial trichoepithelioma typically begin developing tumors during childhood or adolescence. The progression and impact of these tumors include:

• Location: The tumors mostly appear on the face, especially in the folds in the skin between the nose and lips (nasolabial folds, sometimes called smile lines), but may also occur on the neck, scalp, or trunk.
• Growth: They may grow larger and increase in number over time.
• Functional Impact: In severe cases, the tumors may get in the way of the eyes, ears, nose, or mouth and affect vision, hearing, or other functions.
• Psychological Impact: The growths can be disfiguring and may contribute to depression or other psychological problems.
• Gender Differences: For reasons that are unclear, females with multiple familial trichoepithelioma are often more severely affected than males.

Frequency

Multiple familial trichoepithelioma is a rare disorder; its prevalence is unknown.

Causes and Genetics

Multiple familial trichoepithelioma can be caused by mutations in the CYLD gene. This gene provides instructions for making a protein that helps regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins that help protect cells from self-destruction (apoptosis) in response to certain signals. In regulating the action of nuclear factor-kappa-B, the CYLD protein allows cells to respond properly to signals to self-destruct when appropriate, such as when the cells become abnormal. By this mechanism, the CYLD protein acts as a tumor suppressor, which means that it helps prevent cells from growing and dividing too fast or in an uncontrolled way.

The genetic development of the condition involves the following process:

• People with CYLD-related multiple familial trichoepithelioma are born with a mutation in one of the two copies of the CYLD gene in each cell. This mutation prevents the cell from making functional CYLD protein from the altered copy of the gene.
• Enough protein is usually produced 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 involving the other copy of the CYLD gene must occur in certain cells during a person's lifetime.
• When both copies of the CYLD gene are mutated in a particular cell, that cell cannot produce any functional CYLD protein. The loss of this protein allows the cell to grow and divide in an uncontrolled way to form a tumor.
• In people with multiple familial trichoepithelioma, a second CYLD mutation typically occurs in multiple cells over an affected person's lifetime, leading to the growth of skin appendage tumors