Gorlin Syndrome

Basal Cell Nevus Syndrome (Gorlin Syndrome)

The risk for ovarian cancer and skin cancer is increased with basal cell nevus syndrome (also called Gorlin syndrome and nevoid basal cell carcinoma), a rare autosomal dominant cancer genetic syndrome. Features associated with basal cell nevus syndrome may include the following:

• Development of more than two basal cell carcinomas (cancer of the outer layer of the skin) before the age of 20

• Cysts in the jaw

• Characteristic facial appearance

• Calcification of the falx (a variation in the appearance of the skull that is visible on x-rays)

• Pits in the palms and soles of the feet

• Macrocephaly (enlarged head size) 

• Rib or vertebral abnormalities

• Increased risk of medulloblastoma

• Increased risk of ovarian fibromas (benign, or noncancerous, tumors)

Basal cell nevus syndrome is caused by changes in a tumor suppressor gene, called PTCH, located on chromosome 9. Mutations in this gene may increase the risk of some cancers.

Tumor suppressor genes usually control cell growth and cell death. Both copies of a tumor suppressor gene must be altered, or mutated, before a person may develop cancer. With basal cell nevus syndrome, the first mutation is inherited from either the mother or the father in 70 percent to 80 percent of cases. In 20 percent to 30 percent of cases, the first mutation is not inherited and arises de novo (for the first time) in the fertilized egg from which the person with symptoms was conceived. Whether de novo or inherited, this first mutation is present in all of the cells of the body and, as such, is called a germline mutation.

Whether a person who has a germline mutation will develop cancer and where the cancer(s) will develop depends upon where (which cell type) the second mutation occurs. For example, if the second mutation is in the skin, then skin cancer may develop. If it is in the ovary, then ovarian cancer may develop. The process of tumor development actually requires mutations in multiple growth control genes. Loss of both copies of PTCH is just the first step in the process. What causes these additional mutations is unknown. Possible causes include chemical, physical, or biological environmental exposures (such as sunlight) or chance errors in cell replication.

Some individuals who have inherited a germline tumor suppressor gene mutation may never develop cancer because they never get the second mutation necessary to knock out the function of the gene and start the process of tumor formation. This can make the cancer appear to skip generations in a family, when, in reality the mutation is present. People with a mutation, regardless of whether they develop cancer, however, have a 50/50 chance to pass the mutation on to the next generation.

It is also important to remember that the gene responsible for basal cell nevus syndrome is not located on the sex chromosomes. Therefore, mutations can be inherited from the mother or the father's side of the family.