Hereditary Cancer Predisposition Program at the Cancer Center

Nevoid Basal Cell Carcinoma Syndrome (NBCCS)

What is nevoid basal cell carcinoma syndrome (NBCCS)?

Nevoid basal cell carcinoma syndrome, also known as “Gorlin syndrome," is a hereditary cancer syndrome characterized by:

In addition to developing one or more basal cell carcinomas, individuals with nevoid basal cell carcinoma syndrome are also at increased risk to develop other tumor types including:

Because nevoid basal cell carcinoma syndrome is hereditary, the risk of developing features associated with it can be passed from generation to generation in a family. The clinical findings of nevoid basal cell carcinoma syndrome can vary greatly within a family, with some affected individuals having only palmar or plantar pits, while others develop keratocysts, basal cell carcinomas, or more extensive manifestations.

What causes nevoid basal cell carcinoma syndrome (NBCCS)?

Nevoid basal cell carcinoma syndrome is caused by alterations, also known as mutations, at specific areas within an individual’s genetic information. Each of us has a large amount of genetic information that is organized into smaller segments known as “genes.” Genes provide the necessary instructions that our cells require to perform their different functions within our bodies.

In 50 to 90 percent of patients with nevoid basal cell carcinoma syndrome, the disorder develops as the result of alterations in a specific gene known as PTCH1, located on chromosome 9 at position q22.3. The PTCH1 gene has the ability to produce an essential protein involved in a series of reactions within cells that gives them the information they need to ensure that an embryo develops properly. The protein produced by PTCH1 acts as a “tumor suppressor," which means that it helps to keep cells from growing and dividing too quickly and it promotes cell death. It has a fundamental role in controlling the growth and development of normal tissues, specifically the skin, brain and jaw.

With the exception of egg and sperm cells, each cell of the body normally has two working copies of the PTCH1 gene. Patients with nevoid basal cell carcinoma syndrome carry an alteration in one copy of the PTCH1 gene in all the cells of their body. Patients are born and develop normally, but are at an increased risk to develop non-cancerous and cancerous growths. These growths are believed to develop because, over time, the second working copy of the PTCH1 gene may become altered within one or more cells. This can lead to abnormal growth of the affected cells, increasing their chance to become cancerous.

How is nevoid basal cell carcinoma syndrome (NBCCS) inherited?

A person carrying an alteration in one copy of the PTCH1 gene has a 50 percent (or 1 in 2) chance of passing this same alteration on to each of his or her children. Children who inherit the altered gene copy will have nevoid  basal cell carcinoma syndrome and will therefore be at increased risk to develop cancer and other features associated with this condition.

Approximately 70 to 80 percent of patients with nevoid  basal cell carcinoma syndrome inherit an altered copy of the PTCH1 gene from a parent who also has the syndrome. In the remaining 20 to 30 percent of patients, there is no family history of nevoid  basal cell carcinoma syndrome. In these individuals, nevoid  basal cell carcinoma syndrome likely results from presence of a “new mutation” in one copy of PTCH1. Although these individuals will be the first ones in their family to carry the genetic change, each of their future offspring will now have a 50 percent chance to inherit the same genetic change.

How do you diagnose nevoid basal cell carcinoma syndrome (NBCCS)?

The diagnosis of nevoid basal cell carcinoma syndrome relies primarily on the presence of certain clinical symptoms, which are grouped into major and minor diagnostic criteria. A diagnosis of nevoid  basal cell carcinoma syndrome can be made based on the presence of two major and one minor diagnostic criteria or one major and three minor criteria (Evans et al., 1993):

Major criteria

Minor criteria

Basal cell carcinomas (BCCs)

Basal cell carcinomas can appear in early childhood, but more often appear between puberty and 35 years of age, with the mean age of onset being 25 years. Basal cell carcinomas include the following features:

Basal cell carcinomas are typically treated by surgical removal when the number of lesions is limited. Other therapies may be utilized, but radiation therapy should always be avoided in individuals with nevoid basal cell carcinoma syndrome as new tumors can arise in the radiation fields even after many years.  

Keratocysts

Jaw cysts, known as keratocysts, are a representative sign of nevoid basal cell carcinoma syndrome, and are found in 90 percent of affected individuals. They typically occur in the first and second decades of life. Jaw cysts rarely occur after 30 years. Keratocysts should be surgically removed because if left untreated, they can lead to disruption of the teeth and fracture of the jaw.

Other clinical features

Skeletal abnormalities

Nevoid basal cell carcinoma syndrome is characterized by skeletal abnormalities, such as bifid ribs (ribs that are split into two pieces) and wedge-shaped vertebrae. Skeletal defects are typically only seen with the use of X-ray films and may be helpful in making the diagnosis.

Approximately 5 percent of individuals with nevoid basal cell carcinomas are found to have other malformations, including cleft lip/palate, polydactyly, or other eye abnormalities.

Other tumors

Other tumors, such as cardiac and ovarian fibromas, have been reported in approximately 2 and 20 percent of patients with nevoid basal cell carcinoma syndrome, respectively. Cardiac fibromas are usually present at birth or soon after and can be asymptomatic or cause complications. Ovarian fibromas are usually diagnosed during pregnancy or delivery and may cause torsion (twisting) of the ovary but they are not thought to affect fertility. They can become very large and calcified but rarely transform to a malignant tumor.

A detailed review of an individual’s medical and family history becomes important in diagnosing nevoid basal cell carcinoma syndrome. A doctor or genetic counselor may construct a pedigree, or a multi-generation family tree, that indicates which members of the family have developed cancer, the types of cancer and the ages of onset, as well as the presence of any clinical manifestations. If the pattern of clinical features and/or cancers is suggestive of nevoid basal cell carcinoma syndrome, the physician or counselor may recommend that genetic testing be performed.

How does one test for nevoid basal cell carcinoma syndrome (NBCCS)?

In order to confirm on a molecular level that an individual has nevoid  basal cell carcinoma syndrome, he or she can undergo the process of genetic testing:

How test results are used

In patients carrying a diagnosis of nevoid basal cell carcinoma syndrome, approximately 50 to 90 percent of individuals will have a mutation or deletion involving PTCH1. However, it is important to remember that not all patients with nevoid basal cell carcinoma syndrome carry a detectable alteration in PTCH1. There are likely to be additional, undiscovered genes that play a role in the development of the remaining 10 to 50 percent of patients with the syndrome. Therefore, the failure to identify an alteration in the PTCH1 gene does not exclude the diagnosis of nevoid basal cell carcinoma syndrome.

PTCH1 genetic test results can also provide important information for other family members. Knowing the specific alteration that is present in an individual with nevoid basal cell carcinoma syndrome allows for other family members to undergo testing to determine whether they also carry the alteration and could therefore develop the features of nevoid basal cell carcinoma syndrome.

Reproductive options

Reproductive options exist for an individual with an alteration in the PTCH1 gene who does not wish to pass this alteration on to future children:

What are the cancer risks in children and adults with nevoid basal cell carcinoma syndrome (NBCCS)?

The primary cancer risk in nevoid  basal cell carcinoma syndrome is the development of one or more basal cell carcinomas. While most basal cell carcinomas can be effectively treated and cured, on rare occasions, they can spread to other parts of the body and be much more difficult to eradicate.

Individuals with nevoid basal cell carcinoma syndrome are also at an increased risk to develop:

Recommended cancer screening protocol for children and adults with nevoid basal cell carcinoma syndrome (NBCCS)

Regardless of whether one decides to pursue testing for PTCH1 mutations, it is strongly recommended that an individual with nevoid  basal cell carcinoma syndrome consider the following evaluation and surveillance recommendations, which are included in the Consensus Statement from the First International Colloquium on Basal Cell Nevus Syndrome (Bree & Shah, 2011). It is important to note that these are only recommendations and should be discussed and performed in consultation with a healthcare provider familiar with nevoid basal cell carcinoma syndrome. The most common lesions accounting for the syndrome are usually not life-threatening, but surveillance and evaluation is still warranted:

In addition to the above recommended cancer surveillance guidelines, children and adults with nevoid  basal cell carcinoma syndrome should be encouraged to lead as healthy a lifestyle as possible with avoidance of exposure to the sun and ionizing radiation, which increase the likelihood of developing basal cell carcinomas. Patients and parents should be alert to signs and symptoms of basal cell carcinomas and pursue medical attention promptly should these occur. Early treatment of basal cell carcinomas is essential to prevent cosmetic problems. The priorities of treatment are to ensure complete eradication of aggressive basal cell carcinomas, and to preserve normal tissue to prevent disfigurement. Surgical excision can be supplemented by a number of other possible treatments including cryotherapy and laser treatment for early lesions as well as photodynamic therapy.

Support resources for nevoid basal cell carcinoma syndrome (NBCCS)

BCCNS Life Support Network
P.O. Box 321
Burton, OH 44021
Phone: 1-866-834-1895
E-mail: info@bccns.org
www.gorlinsyndrome.org

National Basal Cell Nevus Support (NBCCS Support Network)
162 Clover Hill Street
Marlboro, MA 01752
Phone: 1-800-815-4447
Email: Souldansur@aol.com

The Gorlin Syndrome Group
11 Blackberry Way
Penwortham
Preston
Lancashire
PR1 9LQ
United Kingdom
England Phone: (44) 1772 496849
E-mail: info@gorlingroup.co.uk
www.gorlingroup.org

Additional sources of information for Nevoid Basal Cell Carcinoma Syndrome (NBCCS):
GeneReviews: Nevoid Basal Cell Carcinoma Syndrome
National Library of Medicine Genetics Home Reference: Gorlin syndrome

References

Evans DG, Ladusans EJ, Rimmer S, Burnell LD, Thakker N, Farndon PA. Complications of the naevoid basal cell carcinoma syndrome: results of a population based study. J Med Genet. 1993 Jun;30(6):460-4. Cited in PubMed; PMID 8326488. Read the article

Bree AF, Shah MR. Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). Am J Med Genet Part A. 2011 Sep;155A(9):2091-7. doi: 10.1002/ajmg.a.34128. Epub 2011 Aug 10. Read the article

Reviewed by: Kim Nichols, MD, Kristin Zelley, MS
Date: September 2012

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