Basal Cell Nevus Syndrome (Gorlin Syndrome)

Basal Cell Nevus Syndrome (Gorlin Syndrome)

The risk for childhood brain tumor,
ovarian tumors, and skin cancer is increased with basal cell nevus syndrome (also
called
Gorlin syndrome or nevoid basal cell carcinoma). This is a rare autosomal dominant
cancer
genetic syndrome. Features linked to basal cell nevus syndrome may include:

  • Development of more than 2 basal
    cell carcinomas (cancer of the outer layer of the skin) before age 20

  • Cysts in the jaw

  • Characteristic facial appearance

  • Calcification of the falx (a
    variation in the appearance of the skull that can be seen on X-rays)

  • Pits in the palms of the hands
    and soles of the feet

  • Macrocephaly (enlarged head size) 

  • Rib or vertebral abnormalities

  • Increased risk of
    medulloblastoma (cancerous or malignant brain tumor) during childhood

  • Increased risk of cardiac or
    ovarian fibromas (noncancer or benign tumors)

Basal cell nevus syndrome is caused by
changes in a tumor suppressor gene called PTCH1. It is located on chromosome 9 or
the SUFU
mutation gene.

Molecular genetic testing of PTCH1 or
SUFU is available on a clinical basis. 

Tumor suppressor genes often control
cell growth and cell death. Every person is born with two copies of each tumor suppressor
gene. One is inherited from the mother and one from the father. Both copies of a tumor
suppressor gene must be changed (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 happens for the first time in the affected person. Whether inherited
or not,
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 will develop depends on where (which
cell
type) the second mutation happens. For instance, if the second mutation is in the
skin,
then skin cancer may develop. If it’s 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. Experts don’t
know what
causes these additional mutations. Possible causes include chemical, physical, or
biological environmental exposures (such as sunlight). Or there may be chance errors
when
cells copy themselves.

Some people who have inherited a
germline tumor suppressor gene mutation may never have cancer. This is because they
never
get the second mutation needed to knock out the function of the gene and start the
process
of tumor formation. This can make the cancer seem to skip generations in a family.
But the
mutation is still there. People with a PTCH1 mutation may or may not have cancer.
But they
always have a 50% chance of passing the mutation on to each of their children.

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

If you have a family history of
cancers, discuss this with your healthcare provider. Ask if you should be screened
for a
familial cancer syndrome. Also ask if you should be screened for the development of
certain
tumors.