Juvenile polyposis syndrome (JPS) is a hereditary condition identified by the presence of benign (non-cancerous) polyps in the gastrointestinal tract, most commonly in the colon. Polyps can also occur in the stomach, small intestine and rectum. In addition to polyps, people with juvenile polyposis syndrome are at an increased risk for developing specific types of cancer, including:
Because juvenile polyposis syndrome is hereditary, the risk of developing the features associated with JPS can be passed from generation to generation in a family.
Juvenile polyposis syndrome is caused by alterations (also known as mutations) at specific areas within a person'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 need to perform their different functions within our bodies.
In 60 percent of patients, the underlying cause of juvenile polyposis syndrome is unknown. In the other 40 percent of patients, JPS develops as the result of mutations in one of two different genes, BMPR1A and SMAD4. BMPR1A is located on chromosome 10 at position q22.3-23.2 and SMAD4 is located on chromosome 18 at position q21.1.
The BMPR1A gene produces a protein known as a cell surface receptor. This protein and the protein encoded by the SMAD4 gene act as tumor suppressors, which means that they help to keep cells from growing and dividing too quickly. They also promote cell death.
With the exception of egg and sperm cells, each cell of the body normally has two working copies of both the BMPR1A and SMAD4 genes. In patients with juvenile polyposis syndrome, however, each cell contains only one working copy of either BMPR1A or SMAD4. While the second copy is present, it is altered so that it does not function properly. Patients are born and develop normally, but are at an increased risk to develop both non-cancerous and cancerous growths. These growths are believed to develop because, over time, the second working copy of either the BMPR1A or SMAD4 genes may become altered within one or more cells. This can lead to abnormal growth of the affected cells, increasing their chance to form tumors or cancers.
A person carrying an alteration in one copy of the BMPR1A gene or in one copy of the SMAD4 gene has a 50 percent chance of passing this same alteration on to each of his or her children. Children who inherit the altered gene copy will have juvenile polyposis syndrome and therefore will be at increased risk to develop polyps and other features associated with this condition.
Approximately 75 percent of patients with juvenile polyposis syndrome (JPS) inherit an altered copy of the BMPR1A or SMAD4 gene from a parent who also has JPS. In the remaining 25 percent of patients, there is no family history of juvenile polyposis syndrome (JPS). In these individuals, juvenile polyposis syndrome (JPS) likely results from the development of a new mutation in one copy of either BMPR1A or SMAD4. Although these individuals will be the first ones in their family to carry the genetic change, each of their future offspring will have a 50 percent chance of inheriting the genetic alteration .
The diagnosis of juvenile polyposis syndrome relies primarily on the presence of certain clinical findings, including hamartomatous intestinal polyps (non-cancerous tissue masses) and/or a family history of JPS.
Juvenile polyposis syndrome is clinically diagnosed if any one of the three following findings is present:
In individuals with juvenile polyposis syndrome, juvenile polyps mainly involve the colon, but can also be seen in the stomach, small intestine and rectum. This type of polyp tends to retain mucous and is inflamed, which causes bleeding when the stool passes by the polyp and some of the surface cells shed. Juvenile polyps can develop in infancy and into adulthood, but most individuals with juvenile polyposis syndrome will have polyps by the age of 20 years. While some individuals with juvenile polyposis syndrome may only have four or five polyps throughout their lifetime, others can have over 100. The polyps associated with juvenile polyposis syndrome are most often benign; however, they can change into a malignant cancer.
A careful and detailed review of an individual’s medical and family history is important in diagnosing juvenile polyposis 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 juvenile polyposis syndrome, the physician or counselor may recommend that genetic testing be performed.
There is a condition related to juvenile polyposis syndrome that is also caused by alterations in the SMAD4 gene (it is not associated with alterations in the BMPR1A gene). This condition is known as combined juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (combined JPS/HHT syndrome). It is estimated that 15-22 percent of individuals with a genetic alteration in SMAD4 may have combined JPS/HHT syndrome. In addition to the features of juvenile polyposis syndrome (GI bleeding, gastric and colorectal polyps), individuals with combined JPS/HHT syndrome can have variable features of another condition known as hereditary hemorrhagic telangiectasia (HHT), which include:
The features of HHT may manifest in early childhood. The frequency of each of these HHT-associated features in individuals with combined JPS/HHT syndrome has not been well-established; however pulmonary AVMs appear to be more common while nosebleeds and telangiectases have not been consistently reported in individuals with combined JPS/HHT syndrome.
In order to confirm on a molecular level that an individual has juvenile polyposis syndrome, he or she can undergo the process of genetic testing:
About 40 percent of patients diagnosed with juvenile polyposis syndrome will have a mutation in either of these two genes (20 percent will have mutations in BMPR1A and 20 percent will have mutations in SMAD4). However, it is important to remember that not all patients with juvenile polyposis syndrome carry a detectable alteration in BMPR1A or SMAD4. There are likely to be additional, undiscovered genes that play a role in the development of JPS for the remaining 60 percent of patients. Therefore, the failure to identify an alteration in the BMPR1A or SMAD4 genes does not exclude the diagnosis of juvenile polyposis syndrome (JPS).
BMPR1A and SMAD4 genetic test results can also provide important information for other family members. Knowing the specific alteration that is present in an individual with juvenile polyposis syndrome allows other family members to undergo testing to determine whether they also carry the alteration and could therefore develop the features of juvenile polyposis syndrome.
Reproductive options do exist for a person with an alteration in the BMPR1A or SMAD4 gene who does not wish to pass this alteration on to future children:
While the polyps associated with juvenile polyposis syndrome (JPS) are most often benign, they can change into a malignant cancer. Colorectal cancer is the most common cancer seen in individuals with juvenile polyposis syndrome, but cancers in other parts of the digestive system have also been described, such as cancers of the stomach, upper gastrointestinal tract and pancreas.
The risk for families with juvenile polyposis syndrome to develop gastrointestinal cancers ranges from 9 percent to 50 percent. The incidence of gastric cancer in those with gastric polyps is 21 percent. (Howe et al., 1998a)
If left untreated, polyps can cause bleeding and anemia (lowering of the levels of red blood cells). Routine colonoscopy and removal of the polyps reduces the risk of bleeding, blockage of the intestines, and/or development of colon cancer. Individuals with a large number of polyps may require removal of all or part of the colon or stomach, based on where the polyps are located.
Regardless of whether one decides to pursue testing for BMPR1A or SMAD4 mutations, the following surveillance recommendations, which are listed on the www.genetests.org Web site, are strongly recommended for individuals who carry a clinical diagnosis of JPS or who have a family history of JPS:
In addition to following recommended cancer surveillance guidelines, children and adults with juvenile polyposis syndrome should be encouraged to lead as healthy a lifestyle as possible, avoiding excess sun exposure and tobacco use. Patients and parents should be alert to signs of illness and pursue medical attention promptly should these occur.
We recommend that children with a diagnosis of juvenile polyposis, or those suspected of having juvenile polyposis, contact the Division of Gastroenterology, Hepatology and Nutrition at The Children's Hospital of Philadelphia to discuss issues related to the management of this condition. Please call 215-590-3630 to schedule an appointment.
Adults who have juvenile polyposis or who would like more information about juvenile polyposis may contact the Gastrointestinal (GI) Cancer Risk Evaluation Program at the Hospital of the University of Pennsylvania by calling the coordinator, Samantha Halter, at 215-898-0154 or email@example.com.
American Cancer Society (for information on regional support)
1599 Clifton Rd. NE
Atlanta, GA 30329
Colon Cancer Alliance
1200 G Street, NW
Washington, DC 20005
IMPACC (Intestinal Multiple Polyposis and Colorectal Cancer)
P.O. Box 11
Conyngham, PA 18219
Howe, J.R., et al. (1998a). The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol., 5, 751-56.
Reviewed by: Kim Nichols, MD, Kristin Zelley, MS
Date: September 2012