Juvenile Polyposis Syndrome

What is juvenile polyposis syndrome (JPS)?

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:

  • Colorectal cancer
  • Gastric (stomach) cancer
  • Upper gastrointestinal tract (stomach and esophagus) cancer
  • Pancreatic cancer

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 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 children 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 mutated and does not function properly.

Children with only one working copy of either BMPR1A or SMAD4 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 one remaining 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.

How is juvenile polyposis syndrome (JPS) inherited?

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 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 mutation.


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:

  • More than five juvenile polyps in the colorectum
  • Multiple juvenile polyps throughout the gastrointestinal tract
  • Any number of juvenile polyps and a family history of juvenile polyps

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 JPS will have polyps by the age of 20. Some individuals with JPS may only have four or five polyps throughout their lifetime, others can have more than 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 type of cancer developed
  • The age of cancer onset
  • 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 genetic testing be performed.

Testing for juvenile polyposis syndrome (JPS)?

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 which includes:

  • A blood or saliva sample is obtained from an affected individual.
  • DNA is isolated from the sample and the two copies of the both the BMPR1A and SMAD4 genes are evaluated using a variety of methods and compared to the normal reference sequences for BMPR1A and SMAD4.
  • If a mutation in either BMPR1A or SMAD4 is identified, the genetic counselor can next examine whether the alteration has been previously reported in other individuals with juvenile polyposis syndrome.

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.

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 JPS 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.

Related conditions

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 people 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:

  • Telangiectasias (small dilated blood vessels under the skin or mucous membranes)
  • Arterio-venous malformations (AVMs) (larger blood vessel abnormalities) involving the lungs, liver, brain or gastrointestinal tract
  • Epistaxis (nosebleeds)
  • Intracranial bleeding

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.

Reproductive options

Reproductive options do exist for people with an alteration in the BMPR1A or SMAD4 gene who do not wish to pass this alteration on to future children:

  • Prenatal diagnosis — DNA is isolated from the cells of the developing baby though one of two procedures (chorionic villus sampling [CVS] or amniocentesis) and is analyzed for alterations in the BMPR1A or SMAD4 gene. With appropriate counseling, a parent can then decide whether to carry the pregnancy to term or to end the pregnancy.
  • Preimplantation genetic diagnosis (PGD) — For couples using in vitro fertilization to become pregnant, embryos can be tested for genetic disorders before transferring them into the uterus. Only healthy embryos carrying two working copies of the BMPR1A and SMAD4 genes would be implanted.

Before proceeding with prenatal testing or PGD, a BMPR1A or SMAD4 mutation must be identified in a parent with juvenile polyposis syndrome.

Cancer risks

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)

Cancer screening protocol for children and adults

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 are strongly recommended for anyone with a clinical diagnosis of JPS or who has a family history of JPS:

  • Monitoring for rectal bleeding and/or anemia, abdominal pain, constipation, diarrhea or change in stool size, shape and/or color (any of these symptoms could warrant additional screening).
  • Complete blood counts (CBC), colonoscopy, and upper endoscopy (procedure that allows for visualization of the inside lining of one’s digestive tract) beginning in the mid-teens (age 15) for baseline screening and repeated every 3 years into adulthood. These tests should be performed before age 15 if symptoms arise earlier.
  • If only one or a few polyps are identified, the polyps should be removed. Subsequently, screening should be done annually until no additional polyps are found, at which time screening every 3 years may resume.
  • If many polyps are identified, removal of most of the colon or stomach may be necessary. Subsequently, screening should be done annually until no additional polyps are found, at which time screening every 3 years may resume.
  • Individuals with features of combined JPS/HHT syndrome or with a known SMAD4 mutation can consider following HHT surveillance guidelines. Surveillance and treatment for features of HHT should be discussed with a physician with experience in the management of patients with HHT.

In addition to following recommended cancer surveillance guidelines, children and adults with JPS 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.

Available support

For children

We recommend children with a diagnosis of juvenile polyposis syndrome, or those suspected of having juvenile polyposis, contact CHOP's Division of Gastroenterology, Hepatology and Nutrition.

For adults

Adults who have JPS 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.


Howe, J.R., et al. (1998a). The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol., 5, 751-56.

Providers Who Treat Juvenile Polyposis Syndrome