Nevoid Basal Cell Carcinoma Syndrome

Cancer risk with nevoid basal cell carcinoma syndrome 

People with NBCCS are at higher risk for cancerous tumors such as:

• Medulloblastoma, a brain tumor that occurs in about 5% of children with this syndrome. It usually occurs around age 2.
• Basal cell carcinoma, the most common form of skin cancer, happens in about 90% (9 of 10) of those with NBCCS. It usually starts in their teenage years.

People with NBCCS also have a higher risk for these non-cancerous tumors:

• Painless cysts in the jaw, called keratocysts, which happen in 90% (9 of 10) of people, usually in the teenage years and younger.
• Tumors in the connective tissue (fibromas) of the ovaries, which happen in 20% (2 of 10) of females. Fibromas of the heart happen in 2% of people and are usually present at birth.

Although people with NBCCS are at a higher risk for tumors, some people never develop them.

Symptoms of nevoid basal cell carcinoma syndrome

People with NBCCS may have some or all of the following:

• Small pits in the palms of the hands or soles of the feet
• Large head size (macrocephaly), which may develop if they have too much fluid in their brain (hydrocephalus)
• Distinct facial features, such as wide-set eyes, a jaw that juts out, and a prominent forehead
• Tiny white cysts (bumps), called milia, around the cheeks, eyes, and lips
• Problems with their ribs and spine
• Extra fingers and toes
• Eye conditions, such as cataracts, “lazy” eye, a very small eyeball, or missing certain parts of the eye
• Cleft lip
• Cleft palate

Most people with NBCCS have only some of these features.

Causes of nevoid basal cell carcinoma syndrome 

NBCCS is caused by changes in 1 of 3 genes that make it not work correctly. These genes are called PTCH1, PTCH2, or SUFU. They carry important information that controls how cells grow, divide, and die. They also help an embryo develop during pregnancy, especially development of the jaw, skin, and brain.

How nevoid basal cell carcinoma syndrome is inherited

Most people without NBCCS carry 2 normal copies for each of the PTCH1, PTCH2, and SUFU genes in their cells. One copy is inherited from the mother, and the other comes from the child’s father.

Children who do have NBCCS inherit 1 normal copy of PTCH1, PTCH2, or SUFU and 1 other copy of one of these genes that is changed (mutated). This mutation causes the gene to not work right. So, it is harder for cells to control their growth and functions.

Most children with NBCCS inherit their mutation from a parent who also has the disorder. About 20–30% of children have a new mutation that did not come from a parent. These children have no history of this disorder in their family. In these cases, the change happened either in:

• An egg or sperm that formed the child
• One of the child’s cells before they were born

These children are the first in their families to have NBCCS.

As people with NBCCS get older, the remaining, normal copy of the PTCH1, PTCH2, or SUFU gene might change within some of their cells. When that happens, it is hard for cells to control their growth, and tumors may develop. People with NBCCS may have changes to their cells in places like the skin or the brain. This is why people with NBCCS have a greater risk of developing tumors such as basal cell carcinomas or medulloblastoma.

Diagnosis of nevoid basal cell carcinoma 

Health history

A health care provider may suspect that your child has NBCCS after studying their medical and family cancer history.

This information helps the health care provider and the genetic counselor know if:

• There are more tumors than normal in your family
• These tumors happened at a younger age than expected
• The types of tumors are those seen with NBCCS
• There are family members who have clinical signs of NBCCS

Your child may also need MRI, x-rays, ultrasounds, or evaluation by other specialists.

Your provider or genetics counselor may recommend genetic testing if they suspect NBCCS. Learn more about types of genetic tests.

Genetic testing for nevoid basal cell carcinoma syndrome

A blood sample is sent to a genetic testing lab. The lab runs genetic tests that look for changes in the PTCH1, PTCH2, and SUFU genes.

If your child has a mutation in 1 of these genes, a genetic counselor will work with your family to:

• Find out if other family members should consider testing for a PTCH1, PTCH2, and SUFU mutation
• Help your family understand their increased cancer risk
  
• Give you information to help with your decisions about prenatal genetic testing

Genetic testing before or during pregnancy

No matter how people with NBCCS got their PTCH1, PTCH2, or SUFU mutation, they have a 50% (1 in 2) chance of passing it on to their children. Parents can get prenatal testing to find out if their pregnancy is affected by a known PTCH1, PTCH2, or SUFU mutation.

Testing may take place before pregnancy occurs or after the embryo has formed.

You should work with a genetic counselor to review the pros and cons of the test. The genetic counselor can also help you prepare for the test results.

Testing before pregnancy is called preimplantation genetic testing (PGT). This special type of genetic testing is done along with in vitro fertilization (IVF). PGT tests embryos for a known PTCH1, PTCH2, or SUFU mutation before a provider places the embryo into the uterus.

Testing during pregnancy can help providers see if a pregnancy has a known PTCH1, PTCH2, or SUFU mutation. A doctor gathers cells from the pregnancy in 1 of 2 ways:

• Chorionic villus sampling (CVS) is done during the first 3 months of pregnancy (1st trimester).
• Amniocentesis is done after the first 3 months of pregnancy (2nd trimester or later).

After tissue collection, the lab checks the sample for a mutation in PTCH1, PTCH2, or SUFU. Both tests carry minor risks. Discuss these risks with an experienced health care provider or a genetic counselor.

Special concerns for genetic testing

Take time to think carefully about the benefits and risks of genetic testing. Speak with a genetic counselor before testing. If you decide to get tested, talk with your health care provider or a genetic counselor about your results so you can understand what they mean.

Sometimes, children or adults with NBCCS feel sad, anxious, or angry after getting their test results. Parents may feel guilty if they pass a mutation in PTCH1, PTCH2, or SUFU genes to 1 or more of their children. People with mutations in these genes may also have trouble getting disability or life insurance.

Read more about genetic discrimination.

Monitoring and follow-up care for nevoid basal cell carcinoma syndrome

Monitoring and follow-up care for NBCCS depends on how severe the disease is, the location of any tumors that may arise, and a person’s overall health. Care may involve managing symptoms with medications and surgical removal of any cancerous tissues or tumors. It may also include other treatments such as chemotherapy to fight any cancers that may develop.

Radiation treatment for NBCCS patients should be avoided if possible.

Because NBCCS is a complex condition, parents should discuss screening options for their child with an experienced doctor who knows this condition well. The goal of screening is to find and treat tumors early. Doing so allows the best outcome for patients. There are clinics throughout the country that specialize in taking care of people with NBCCS.

It is also important that parents also work with a genetic counselor to find experienced health care providers for their child. To find a genetics counselor in your area, visit Personalized Care for Your Genetic Health.

Cancer screening for those with NBCCS

Anyone with this syndrome should be regularly screened. Screening helps us find and treat tumors early so patients have the best outcomes. It can also prevent the growth of tumors that could change a person’s appearance.

We recommend these tumor screenings:

• An echocardiogram (echo) at the time of diagnosis to check for fibromas in the heart. An echocardiogram uses sound waves to take pictures of the heart.
• Magnetic resonance imaging (MRI) of the brain to look for brain tumors in patients with a SUFU mutation. This should be done every 4 months until the person turns 3 years old. Then it should be done every 6 months until the person turns 5 years old. If there are any symptoms, the imaging may be repeated more often.
• Digital panoramic x-rays of the jaw to look for cysts in patients with a PTCH1 or PTCH2 mutation. These should start at age 8 and be repeated every 12–18 months. Digital panoramic x-rays may be used in patients with SUFU mutations, although jaw keratocysts have not been found in those with SUFU mutations.
• Yearly skin exams to look for basal cell carcinoma. Skin exams may begin at age 10 or before if abnormal skin findings are noticed.
• In females, an ultrasound of the ovaries should be done starting at age 18. Ultrasounds should be repeated at the time of pregnancy or if a person has symptoms.

As we learn more about NBCCS, the recommended screenings may change. This is why it is important to get care from a health care provider who has experience monitoring and treating this syndrome.

Living with nevoid basal cell carcinoma syndrome

People with NBCCS have a higher risk for cancer and tumors and should watch closely for general signs or symptoms listed above. They should talk to their care provider if they notice anything unusual. They should monitor their health and adopt healthy habits throughout their lifetime. We recommend that they have regular physical checkups and screenings. When cancer is detected early, we are better able to treat it.

It is critical that people with nevoid basal cell carcinoma syndrome avoid exposure to radiation. When x-rays are needed, people should find a center that can do digital x-rays.

People with NBCCS should be careful about sun exposure:

• Avoid sun exposure during the hours when the sun is most intense.
• Wear protective clothing and a hat.
• Use sunscreen with an SPF of at least 50 when going outside.

Learn more about how to prevent skin cancer.

Problems to watch for

People with NBCCS should watch closely for signs and symptoms that could signal tumors, including:

• Unexplained weight loss
• Loss of appetite
• Aches, pains, lumps, or swelling that cannot be explained
• Headaches, changes in vision, or changes in nerve function that do not go away
• New moles or changes in moles that are already present

It is important to seek medical help if anything unusual appears.

Maintain a healthy lifestyle

Habits that will help you maintain a healthy lifestyle include:

• Eat a healthy diet with lots of fruits and vegetables.
• Get regular exercise.
• Avoid smoking or using tobacco products.
• Avoid secondhand smoke.
• Avoid excessive alcohol use

Nevoid basal cell carcinoma syndrome care at       St. Jude

The St. Jude Cancer Predisposition Program is dedicated to diagnosing and screening children with a genetic predisposition for cancer. Our program offers the best clinical care possible. We engage in cutting-edge research to gain more information about genetic disorders and cancer, and to improve the care and treatment for patients who are affected by these conditions.

Our genetic counselors, clinicians, genetics nurse practitioners, and research assistants work together to provide patients with:

• A complete health history
• A record of cancer that happened over the past 3 generations (family tree or pedigree) to see how diseases were passed down
• Physical exams to check for physical signs of a genetic disease
• Confidential genetic counseling and testing
• Cancer screenings for those with genetic disease to detect and treat cancer as soon as it occurs
• Recommended cancer treatments and ways to reduce cancer risk
• Genetic testing for immediate (1^st degree) relatives (including siblings and parents).

NBCCS increases your child’s risk for tumors and, less commonly, certain cancers. Visit Diseases Treated to learn more about how we treat specific cancer types.

If you have questions about the Genetic Predisposition Clinic and care for NBCCS, email our team at GPTeam@stjude.org.

Resources outside St. Jude