Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a rare condition that’s usually present at birth and may affect multiple parts of the body.

• It typically causes basal cell carcinoma—a type of skin cancer that starts deep in the skin’s basal cells—to develop early in life (usually starting in the teenage or young adult years), and it may come back repeatedly.
• It also comes with an increased risk of developing other cancerous and noncancerous tumors, including a brain cancer called medulloblastoma and noncancerous tumors in the jaw, heart or ovaries.

One in 31,000 people is estimated to have this condition, according to the U.S. National Library of Medicine (NLM). While basal cell carcinoma is the most common type of skin cancer in general, fewer than 1 percent of these cancers are due to Gorlin syndrome.

What are the symptoms of Gorlin syndrome?

Symptoms vary among people with Gorlin syndrome. Some may have many characteristic symptoms and features of the condition, while others have very few. Symptoms may be mild, severe or somewhere in the middle.

People with Gorlin syndrome may have certain distinct features that are either present at birth or become noticeable early in childhood, such as:

• Larger-than-average head
• Unusual facial features, such as a prominent forehead
• Bone abnormalities in the spine, ribs or skull
• Eye problems
• Skin tags
• Small indentations on the hands and feet (pits)

The most common features of this condition are jaw tumors and multiple basal cell carcinomas, which affect about 90 percent of people with Gorlin syndrome, according to the American Society of Clinical Oncology (ASCO). About 5 percent of children with Gorlin syndrome develop medulloblastoma.

Gorlin syndrome tends to start causing basal cell skin cancers when affected individuals are in their teen or young adult years, but the frequency may vary greatly from person to person—some may get thousands of basal cell carcinomas in their lifetime, while others may not get any. During adolescence and young adulthood, people with this condition also commonly develop noncancerous tumors in the jaw, called keratocystic odontogenic tumors, but it’s rare for them to continue developing past age 30.

What causes Gorlin syndrome?

Genetic changes, or mutations, are the cause of Gorlin syndrome. Researchers have identified some of the specific mutations associated with the condition, while others remain unknown. Most people with Gorlin syndrome inherit it from one parent—the parent of an affected individual carries gene mutations associated with Gorlin syndrome and passes those mutations to the child. A person with these mutations has a 50 percent chance of passing them down to every child they may have. More rarely, the condition is due to new mutations that develop randomly in the egg and sperm cells of parents or during fetal development, and aren’t inherited.

About 50 to 85 percent of people with Gorlin syndrome have mutations in a particular gene, called the PTCH1 gene, according to the NLM. The normal role of this gene is to keep cell division and replication under control and prevent cells from reproducing too quickly, which is how tumors form. Mutations in this gene may cause it to lose control of cell growth and division, resulting in the tumor growth that comes with Gorlin syndrome. The causes of other features of Gorlin syndrome are less well understood.

How is Gorlin syndrome diagnosed?

People are typically diagnosed with this syndrome when they have at least two "major" features of the condition and one "minor" feature, or one major feature and three or more minor features.

Major features of Gorlin syndrome

The following symptoms are considered major features of the condition:

• More than two basal cell carcinomas before age 50
• One or more cysts on the jaw bone or other bones
• Abnormal calcium deposits in the brain that are visible on an X-ray
• Depressions (pits) in the palms of the hands or soles of the feet
• A close relative (parent, sibling or child) with Gorlin syndrome

Minor features of Gorlin syndrome

Gorlin syndrome’s minor features are:

• Medulloblastoma
• Larger-than-average head size and prominent forehead
• Cleft lip, cleft palate or extra fingers or toes
• Unusually shaped ribs or spine
• Eye abnormalities, including cataracts, small eyes or tumors in the iris
• Noncancerous (benign) fibrous tumors in the ovaries or heart
• Cysts in the abdomen

How is Gorlin syndrome treated?

Treatment for Gorlin syndrome involves regular checks for signs of cancer and other complications.

Screening for complications

People who have or are suspected of having Gorlin syndrome may undergo the following screening measures, usually starting at an early age:

• Neurologic evaluations to look for medulloblastoma or developmental disabilities
• Regular measurement of head size during childhood
• Annual X-rays of the jaw area to check for cysts
• Skin exams to check for basal cell carcinoma. The care team may determine how often these should be done by looking at the patient’s health history.

Treatment options

The best treatment options for a person with Gorlin syndrome depend on the specific symptoms. Jaw cysts, or odontogenic keratocysts, are typically removed via surgery shortly after they’re found. If not, they may get progressively worse, affecting tooth placement and causing pain and swelling.

The basal cell carcinomas that develop with Gorlin syndrome may be treated with options that include:

• Topical chemotherapy (applying topical medications that destroy cancer cells)
• Surgery (removing the skin cancer)
• Cryotherapy (freezing and killing cancer cells using a topical application of extremely cold liquid nitrogen)
• Electrodesiccation and curettage (using a heated needle to burn cancerous tissue)
• Drugs such as Odomzo^® (sonidegib) and Erivedge^® (vismodegib) (for basal cell cancers that return after surgery or spread within the body and can't be treated with surgery or other options)

Gorlin syndrome patients typically don’t receive radiation therapy, as this treatment may cause more basal cell cancers to grow.

What precautions should people with Gorlin syndrome take?

Gorlin syndrome patients should take extra care to lower their risk of skin cancer, such as avoiding exposure to the sun and protecting the skin during sun exposure. Those with lighter skin need to be particularly cautious. According to ASCO, lighter-skinned people with this condition tend to have a significantly higher risk of basal cell cancers than those with darker skin.