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 or nevoid basal cell carcinoma), a rare autosomal dominant
cancer genetic syndrome. Features associated with basal cell nevus syndrome may include
Development of more than 2 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
Pits in the palms and soles of the feet
Macrocephaly (enlarged head size)
Rib or vertebral abnormalities
Increased risk of medulloblastoma during childhood
Increased risk of cardiac or ovarian fibromas (benign, or noncancerous, tumors)
Basal cell nevus syndrome is caused by changes in a tumor suppressor gene, called
PTCH1. This gene is located on chromosome 9. Mutations in this gene may increase the
risk of some cancers.
Molecular genetic testing of PTCH1 is available on a clinical basis.
Tumor suppressor genes usually control cell growth and cell death. Every person is
born with two copies of each tumor suppressor gene, one inherited from his or her mother
and one from his or her father. 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. This happens in
70% to 80% of cases. In 20% to 30% of cases, the first mutation is not inherited.
It arises for the first time (de novo) in the affected person. Whether de novo or inherited, this first mutation is present in all of the cells of the body from
conception. It is called a germline mutation.
Whether a person who has a germline mutation will develop cancer and where the cancer(s)
will develop depends on where (which cell type) the second mutation happens. 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
needs mutations in multiple growth control genes. Loss of both copies of PTCH1 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 when cells copy themselves.
Some individuals who have inherited a germline tumor suppressor gene mutation may
never develop cancer. This is 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. But, in reality, the mutation
is present. People with a PTCH1 mutation, regardless of whether they develop cancer,
have a 50/50 chance to pass the mutation on to each of their children.
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's side or the father's side of the family.