What is Nevoid Basal Cell Carcinoma Syndrome?
Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is also known as Gorlin syndrome. NBCCS is a hereditary condition characterized by multiple basal cell skin cancers. Other common findings include jaw cysts, pits on the palms of the hands or soles of the feet, calcium deposits in the brain, developmental disability, and skeletal (bone) changes. The appearance of a person with NBCCS may include a larger head size, a prominent forehead, broad bridge of the nose, widely spaced eyes, skin cysts, and small skin bumps called milia. The jaw cysts and basal cell skin cancers may develop in the first ten years of a person’s life, but they may not appear until the teenage years or any time during adulthood. Children with NBCCS may have the appearance features described above, including pits on their hands and feet. There is a small (5%) chance for children with NBCCS to develop a type of brain cancer called medulloblastoma. Rarely, benign (not cancerous) growths in the ovaries and heart may also be found.
Multiple basal cell skin cancers and jaw cysts are the most common features of NBCCS and are present in about 90% of people who have the condition. There are several other features that have been associated with NBCCS. The number of features present and the severity of symptoms can vary among people with NBCCS, even within the same family. People with darker skin with NBCCS may have jaw cysts as the primary feature of the disease and may develop far fewer sun-related basal cell skin cancers than people with lighter skin with NBCCS. Jaw cysts may cause symptoms such as bone deformity, infections and pain, or they may be seen through an x-ray.
What causes NBCCS?
NBCCS is a genetic condition. This means that the cancer risk and other features of NBCCS can be passed from generation to generation in a family. The major gene associated with NBCCS is called PTCH. A mutation (alteration) in the PTCH gene gives a person an increased risk of basal cell skin cancer and other symptoms of NBCCS. Research is ongoing to learn more about NBCCS and to identify other genes involved, such as SUFU.
Sun exposure and radiation therapy increase the number of basal cell skin cancers that a person with NBCCS develops. Some individuals may have thousands of basal cell cancers in areas of skin that are exposed to the sun or radiation therapy.
How is NBCCS inherited?
Normally, every cell has 2 copies of each gene: one inherited form the mother and one inherited from the father. NBCCS follows an autosomal dominant inheritance pattern, in which a mutation happens in only 1 copy of the gene. This means that a parent with a gene mutation may pass along a copy of the normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has up to a 50% chance of having the same mutation. It is also possible that the NBCCS in an individual was caused not by an inherited mutation but, rather, by a spontaneous gene mutation (see below).
Options exist for couples interested in having a child when they know that 1 of them carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to have children who do not carry the mutation. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, one cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos which do not have the mutation. PGD has been in use for over a decade, and more recently has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors for couples to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.
How common is NBCCS?
It is estimated that about one in 40,000 people have NBCCS. As many as 30% of people with NBCCS do not have any family history of the condition. They have a de novo (new) mutation in the PTCH gene.
How is NBCCS diagnosed?
NBCCS is diagnosed when a person has at least 2 major features of NBCCS and one minor feature, or 1 major feature and at least 3 minor features.
Multiple (more than 2) basal cell skin cancers that appear earlier in life than is usual
Increased calcium deposits in the head that can be seen on an x-ray
Jaw or bone cyst(s)
3 or more pits on the palms of the hands or soles of the feet
A parent, sibling, or child with NBCCS
Increased head size and large forehead
Cleft lip or palate, extra fingers or toes
Abnormal shape of the ribs or spinal bones
Eye problems such as cataracts, small eyes, or tumors in the iris
Fibromas, meaning benign fibrous tumors, of the ovaries or heart
If a person has a family history of NBCCS, that person is also suspected of having NBCCS if they have jaw cysts, multiple basal cell skin cancers, pits on the palms of the hands or soles of the feet, or calcium deposits in the head. Genetic testing for mutations in the PTCH gene is available for people suspected to have NBCCS. A mutation in the PTCH gene is found in up to 85% of people diagnosed with NBCCS.
What are the estimated cancer risks associated with NBCCS?
People with NBCCS have a 90% risk of developing multiple basal cell skin cancers. About 5% of children with NBCCS will develop medulloblastoma, a type of brain stem tumor.
Researchers have studied the use of medications that target the so-called “hedgehog pathway”, which is affected by the PTCH mutation in people with NBCCS. There are 2 medications called vismodegib (Erivedge) and sonidegib (Odomzo) that have been approved to treat people with basal cell cancers that have spread in the body or that cannot be treated with surgery or radiation. This treatment is a pill which blocks the activated pathway that results in basal cell cancers. Talk with your doctor for more information about treatment options.
What are the screening options for NBCCS?
Current screening recommendations for people who are known or suspected to have NBCCS include:
Neurologic evaluation every 6 months from birth to age 3, then every year to age 7 to look for signs of medulloblastoma or developmental disability
Measurement of head size regularly throughout childhood
Yearly dental x-rays, beginning at age 8, to look for jaw cysts
At least yearly skin exams to watch for basal cell skin cancer. The frequency of exams will vary based on how many basal cell cancers or other skin problems a person has experienced. Early treatment of basal cell skin cancer reduces the amount of surgery and scarring. Regular exams should begin by the teenage years.
Due to the high risk for multiple skin cancers, people with NBCCS should avoid sun exposure and protect their skin when outside. Learn more about protecting your skin from the sun. People with NBCCS should not receive radiation therapy, as this will increase the risk of basal cell skin cancers.
Screening recommendations may change over time as new technologies are developed and more is learned about NBCCS. It is important to talk to your doctor about appropriate screening tests. In general, if there is a good screening option that doesn’t use radiation, that screening option should be used to avoid skin damage and basal cell cancers.
Learn more about what to expect when having common tests, procedures, and scans.
Questions to ask the doctor
If you are concerned about your risk of skin cancer, talk to your doctor. Consider asking the following questions:
What is my risk of skin cancer?
What can I do to reduce my risk of skin cancer?
What are my options for cancer screening?
If you are concerned about your family history and think you or other family members may have NBCCS, consider asking the following questions:
Does my family history increase my risk of skin cancer?
Does it suggest the need for a cancer risk assessment?
Will you refer me to a genetic counselor or other genetics specialist?
Should I consider genetic testing?
What preventive measures would you recommend?
National Cancer Institute
American Cancer Society
To find a genetic counselor in your area, ask your doctor or visit these websites:
National Society of Genetic Counselors
National Cancer Institute: Cancer Genetics Services Directory