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Gastrointestinal Polyposis Syndromes

  • A group of syndromes characterized by multiple colorectal polyps and an increased risk for colorectal cancer
  • Symptoms include rectal bleeding, blood in stool, weight loss, nausea and/or vomiting, abdominal pain
  • Treatment includes surveillance, surgery, medications
  • Involves Center for Gastrointestinal Cancers, Gastrointestinal and Pancreatic Cancer Prevention Program, Gastroenterology, Medical Oncology

Gastrointestinal Polyposis Syndromes


A gastrointestinal (GI) polyp is an abnormal growth of tissue that projects from the inner lining of the colon, rectum, stomach, or other parts of the digestive (or GI) tract. Polyps may be noncancerous (benign), cancerous (malignant), or precancerous, meaning they may become cancerous. When numerous polyps are present, rather than just one or a few, doctors refer to it as polyposis.

A number of syndromes, collectively known as GI polyposis syndromes, are characterized by the presence of numerous polyps—sometimes hundreds or thousands—in the colon, rectum, and/or other parts of the GI tract. In many cases, the polyps develop at a young age, and people with a GI polyposis syndrome are at increased risk for colorectal cancer and, sometimes, stomach cancer or cancers in other parts of the body.

Because of the increased risk of cancer and young age of onset, those with a polyposis syndrome typically get colonoscopies at a younger age and more frequently than usual. Treatment may also involve surgical removal of the colon and rectum and regular screenings for cancer in other parts of the body. Also, because polyposis syndromes can also cause symptoms in other parts of the body, such as the skin, teeth, and bones, among others, treatment may involve multiple medical specialists.

“Polyposis syndromes often have very distinct and unique features,” says Xavier Llor, MD, PhD, co-director of the Gastrointestinal and Pancreatic Cancer Prevention Program. “A multidisciplinary approach that includes different clinical specialties is essential to provide the best care for patients with these conditions. With proper care, risks to these patients can be minimized and they can have an excellent prognosis.”

What are polyposis syndromes?

There are several GI polyposis syndromes. Doctors classify them based on a number of characteristics, including the age at which they occur, the number and predominant type of polyps involved, whether and how other parts of the body are affected, and family history of polyposis. Mutations in certain genes are involved in most types of GI polyposis.

Some types of GI polyposis syndromes include:

Adenomatous polyposis syndromes. People with these syndromes develop adenomatous polyps, which are classified based on their shape, size, and appearance under a microscope. Adenomatous polyps are benign (noncancerous), though they can become cancerous.

  • Familial adenomatous polyposis (FAP) is caused by a mutation in the adenomatous polyposis coli (APC) gene. In most cases, people with FAP inherit the mutation from one of their parents, though up to 30% of cases are caused by a de novo—or new—mutation in the APC gene. People with a de novo mutation do not have a family history of FAP, though they can pass the mutation (and therefore the condition) to their children.

    There are two types of FAP:
    • Classic FAP is characterized by the presence of numerous—often hundreds or thousands—of polyps in the colon and rectum. The polyps typically begin to appear in childhood or adolescence, usually by age 16, and more polyps develop as people age. Without surgical treatment, the likelihood of developing colorectal cancer is nearly 100% for people with classic FAP. On average, people with classic FAP who remain untreated are diagnosed with colorectal cancer at age 39.
    • Attenuated FAP, or AFAP, is less severe than classic FAP. In AFAP, the lifetime risk of developing colorectal cancer is lower (though still high, at around 80%), and people tend to have fewer colorectal polyps (10 to 100) that typically develop at a later age (mid-to-late 20s). If colorectal cancer develops, it is usually diagnosed at a later age—at age 58, on average—than in those with classic FAP.
    In about 15% of FAP cases, benign tumors, known as desmoid tumors, form in the abdomen. Those with FAP are also at increased risk of developing tumors, which may be benign or malignant (cancerous) in other parts of the body, including the stomach, duodenum (the first part of the small intestine), small intestine, pancreas, thyroid gland, liver, brain, and adrenal glands.

    Dental problems, such as extra or missing teeth from birth or teeth that have not emerged from the gum, may occur. Noncancerous bony growths, called osteomas, may form (especially on the jaw and skull), and noncancerous cysts on the skin, known as epidermoid cysts, can also occur in people with FAP. Some people with FAP have an eye condition called congenital hypertrophy of the retinal pigmented epithelium (CHRPE). CHRPE usually does not cause symptoms, but because it is present from birth, it can be an early sign of FAP or other polyposis syndromes.

    FAP affects between 1 in 8,000 and 1 in 18,000 people and occurs equally in males and females. It accounts for under 1% of colorectal cancer cases in the U.S.
  • MUTYH-associated polyposis (MAP) is an inherited form of polyposis caused by a mutation in the MUTYH gene. As an autosomal recessive condition, a person must inherit a mutated MUTYH gene from both parents to get MAP. It occurs in around one out of every 8,300 births.

    People with MAP typically have 20 to 100 colorectal polyps (though more may be present) and have a 35% to 75% risk of developing colorectal cancer. On average, colorectal cancer develops between ages 45 and 50. The risk of developing cancers of the duodenum, ovaries, skin, and bladder are also increased; the risk for thyroid, breast, and endometrial cancer may also be increased. Rarely, people with MAP can also develop CHRPE, osteomas, desmoid tumors, and epidermoid cysts, among other symptoms.

Hamartomatous polyposis syndromes. These polyposis syndromes are characterized by the presence of multiple hamartomatous polyps—abnormal, benign growths that develop in the GI tract and may progress to cancer.

  • Juvenile polyposis syndrome (JPS) is characterized by the development of five to hundreds of polyps throughout the GI tract, usually by age 20, and an increased risk for colorectal and stomach cancer. For people with JPS, the lifetime risk for colon cancer is around 39%.

    The term “juvenile” does not refer to the age of onset. Instead, it is used because people with JPS develop a type of polyp called “juvenile polyps.”

    JPS is also associated with intestinal malrotation (abnormal twisting of the intestines), telangiectasia (widened blood vessels near the skin surface), hydrocephalus (buildup of fluid in the brain), cleft palate, polydactyly (extra fingers or toes), undescended testicle, nosebleeds, thyroid diseases, aortic aneurysm, mitral valve prolapse, and ventricular septal defect, among other heart conditions.

    JPS is caused by mutations in the SMAD4 and BMPR1A genes. It is an autosomal dominant condition, meaning it affects people who inherit one copy of a mutated gene from one parent. Around three-quarters of people with JPS have a family history of the condition, while about a quarter have de novo mutations. JPS occurs in around 1 out of every 100,000 people.
  • Peutz-Jeghers syndrome (PJS) is characterized by the presence of multiple hamartomatous polyps in the GI tract, signs of feminization in men, such as gynecomastia (breast development), and mucocutaneous pigmentation (dark freckles on the lips, fingers, toes, anus, nose, in and around the mouth, and around the eyes). People with PJS are at increased risk for colorectal cancer, as well as cancers of the stomach, small intestine, pancreas, breast, ovaries, uterus, cervix, lungs, and testicles. By age 64, the risk for colon cancer is 64% while the risks for cancer of the stomach, pancreas, and breast are 29%, 36%, and 54%, respectively.

    Before age 10, people with PJS may develop mucocutaneous pigmentation, and GI polyps may appear by age 10. Symptoms, including nausea, vomiting, abdominal pain, and/or rectal bleeding, often begin between ages 10 and 30.

    PJS is a rare condition, occurring in 1 out of 50,000 to 200,000 people. It is caused by mutations in the STK11 gene and equally affects males and females. As an autosomal dominant condition, people who inherit one mutated gene from one of their parents develop PJS.
  • PTEN hamartoma tumor syndrome (PHTS) refers to a group of disorders caused by mutations in the PTEN gene and is characterized by the presence of hamartomas in the GI tract, skin, and other parts of the body. PHTS is an autosomal dominant condition.

    Disorders that are classified under PHTS include Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and adult Lhermitte-Duclos disease.

    Over 90% of people with PHTS have polyps in the colon. PHTS is also associated with a 9% lifetime risk for colon cancer. The lifetime risk for other cancers is also increased, including breast (85%), thyroid (35%), endometrium (28%), kidney (34%), and skin (melanoma, 6%).
  • Cronkhite-Canada syndrome (CCS). This type of polyposis is an acquired condition (it is not inherited), characterized by the presence of multiple polyps in the GI tract, as well as hair loss affecting the scalp, eyebrows, face, armpits, pubic area, and arms and legs; skin pigmentation; diarrhea; thinning nails; and detachment of finger and toenails from the nail bed. On average, symptoms begin at age 59. It is a rare condition, with over 500 known cases reported around the world since the condition was first described in 1955.

    People with CCS have a 20% to 25% risk of developing colorectal cancer, and the condition has been associated with stomach cancer. Many people with CCS also have an autoimmune disease such as lupus erythematous, rheumatioid arthritis, or scleroderma. It may be caused by an autoimmune disorder.

Serrated polyposis syndrome (SPS). In this polyposis syndrome, multiple serrated polyps, which have a serrated appearance (like the teeth of a saw) when examined under a microscope, arise in the colon. These polyps may become cancerous. SPS is characterized by the presence of five or more serrated polyps (two or more of which measure over 1 cm in diameter) in the lower part of the colon or 20 or more serrated polyps throughout the colon over time. The lifetime risk for colorectal cancer for people with SPS may vary significantly, ranging from 7% to 70%.

Around half of people with SPS have a family history of colorectal cancer, though no definitive genetic cause for SPS has been identified.

There are also other rare polyposis syndromes, including hereditary mixed polyposis syndrome (HMP)S, polymerase proofreading-associated polyposis (PPAP), and NTHL1-associated polyposis (NAP).

What causes polyposis syndromes?

As noted above, many polyposis syndromes are caused by mutations in certain genes. These mutations can alter the function of the affected genes, resulting in an increased risk of developing colorectal polyps and, for many polyposis syndromes, conditions that affect other parts of the body.

In some cases, polyposis syndromes occur sporadically, meaning the affected individuals did not inherit the condition from their parents. Often, sporadic cases of polyposis occur when there is a new mutation in a gene related to one of the polyposis syndromes.

What are the symptoms of polyposis syndromes?

Symptoms may vary depending on the type of polyposis syndrome and patients may initially not have any symptoms. Symptoms related to colorectal and GI polyposis may include:

  • Rectal bleeding
  • Blood in stool
  • Anemia
  • Weight loss
  • Nausea and/or vomiting
  • Abdominal pain
  • Diarrhea
  • Constipation
  • Tenesmus (the feeling of having to pass stools even though the bowels are empty)
  • Protein-losing enteropathy (excess loss of proteins in the blood into the GI tract, leading to limb swelling, fluid buildup in the abdomen, and diarrhea)

The polyposis syndromes often cause symptoms in other parts of the body, as noted above.

How are polyposis syndromes diagnosed?

Diagnosis of polyposis syndromes may involve a review of the patient’s medical history, a physical exam, and one or more procedures or tests. A doctor may suspect a patient has a polyposis syndrome based on their family history, the presence of symptoms and signs that could be caused by a polyposis syndrome, or if multiple colorectal polyps are found during colonoscopy.

If a doctor suspects a patient may have a polyposis syndrome, they may begin to make a diagnosis by asking whether the patient has a family history of colorectal cancer or a polyposis syndrome, what symptoms—if any—are present, and when they began.

During the physical exam, the doctor will look for signs that could indicate a polyposis syndrome. For instance, they may check the skin for freckling, cysts, dental abnormalities, fingernail and toenail thinning, or separation from the nailbed.

Certain tests and procedures are also used to identify and diagnose polyposis syndromes, including:

  • Colonoscopy and/or sigmoidoscopy. These procedures are used to examine the inside of the rectum and colon. If polyps are detected during the exam, they can be removed and then analyzed in a lab to determine whether the tissue is abnormal or cancerous. In a colonoscopy, the provider examines the rectum and the entire colon, whereas in a sigmoidoscopy, the rectum and only the lower part of the colon (called the sigmoid colon) are examined.

    Often, doctors will suspect a polyposis syndrome if 10 or more colorectal polyps are detected over time, multiple polyps are found in other parts of the GI tract, or if polyps are found in a young person with a family history of polyposis.
  • Upper endoscopy. In this procedure, a scope is inserted into the mouth, down the throat, then into the esophagus, stomach, and duodenum. Upper endoscopy is used to look for polyps or other abnormalities in the upper digestive tract. As with colonoscopy and sigmoidoscopy, if polyps are detected, they can be removed for laboratory analysis.
  • Genetic testing. Genetic testing checks for gene variants associated with polyposis syndromes. A gene panel test that checks for variants in multiple genes known to be involved in polyposis syndromes may be used.

    If a polyposis syndrome-associated gene mutation is found, other family members should also undergo genetic testing to determine if they have the same gene mutation.

How are polyposis syndromes treated?

Because the polyposis syndromes can affect various parts of the body, treatment typically involves a multidisciplinary medical team of GI specialists, oncologists, dermatologists, and other specialists.

In general, treatment may include:

  • Surveillance. Because the polyposis syndromes increase the risk for colorectal and other cancers, surveillance is a crucial part of treatment. People with a polyposis syndrome should get colonoscopies or sigmoidoscopies at a younger age and at shorter intervals (often every one to three years) than usual to detect and remove colorectal polyps. For example, people with FAP are usually advised to begin getting these tests when they are between 10-14 years old.

    Depending on the specific polyposis syndrome a person has, additional tests and procedures are recommended to screen for and identify cancer in other parts of the body. These tests may be performed more frequently and begin at a younger age than usual. Tests and procedures vary, depending on the type of cancer, and may include:
    • Thyroid cancer: Regular thyroid ultrasounds
    • Kidney cancer: Regular kidney ultrasounds
    • Skin cancer: Regular skin exams performed by a dermatologist
    • Breast cancer: Regular clinical breast exams, annual mammography, and breast magnetic resonance imaging (MRI) screenings. In some cases, women may undergo a prophylactic mastectomy and/or hysterectomy.
    • Endometrial cancer: Regular endometrial biopsies may be considered.
    • Small intestine cancer: Screening with endoscopy, enteroscopy, or imaging tests
    • Testicular cancer: Annual testicular exams and, for people with PJS, a testicular ultrasound (if there are signs of feminization such as gynecomastia) may be considered
    • Cervical, ovarian, and uterine cancers: Annual pelvic exams and Pap tests
    • Pancreatic cancer: Endoscopic ultrasound of the pancreas or MRI/magnetic resonance cholangiopancreatography (an imaging test that allows health care providers to examine the bile and pancreatic ducts)

People with a polyposis syndrome should see a health care provider for regular checkups and, if necessary, blood work, imaging, or other tests.

  • Colectomy and/or proctocolectomy. The surgical removal of the entire colon (total colectomy), part of the colon (subtotal colectomy), or the colon and the rectum (proctocolectomy) may be done as a preventive measure to prevent colorectal cancer from developing or, if cancer has developed, to eradicate it from the body.
  • Medications. Medication may be used to treat some types of polyposis syndromes.
    • Medications for reducing polyp size, number, and recurrence:
      • Nonsteroidal anti-inflammatory drugs (NSAIDs), such as sulindac, may reduce the number and size of colorectal polyps in people with FAP. It is unknown, however, whether sulindac protects against colorectal cancer.
      • Low-dose aspirin may reduce the chances of a reappearance of polyps in people with FAP after polyp removal during a colonoscopy or sigmoidoscopy.
    • Steroids: Corticosteroids have been used to treat people with CCS. CCS may be caused by an autoimmune disorder, which occur when the body’s immune system mistakenly attacks healthy tissue. Corticosteroids work by suppressing the immune system.
    • Azathioprine: This immunosuppressive drug may be used to treat CCS.

Because the polyposis syndromes can affect many parts of the body beyond the digestive tract, treatment by specialists in other medical fields may be necessary.

What is the outlook for people with a polyposis syndrome?

The outlook for people with a polyposis syndrome varies based on the type of syndrome, its severity, and the timing of diagnosis and treatment. The polyposis syndromes are associated with an increased risk for colorectal cancer and, depending on the specific syndrome, cancers and/or conditions that affect other parts of the body.

In general, the outlook is improved for those who receive an early diagnosis. With active surveillance and timely treatment, people may prevent the onset of colorectal cancer. Periodic cancer screenings can help health care providers detect cancers in other parts of the body at early stages of disease, when it may be easier to treat.

What stands out about Yale's approach to treating polyposis syndromes?

“Yale’s Gastrointestinal and Pancreatic Cancer Prevention Program through its Lynch Syndrome and Polyposis Clinic and Pancreas Cancer Early Detection Clinic take a comprehensive approach to polyposis syndromes, offering state-of-the-art diagnosis, risk assessment, surveillance, and prophylactic measures,” says Yale Medicine gastroenterologist Benjamin Lerner, MD, MHS. “We also collaborate and advise clinicians who care for these patients outside of our program.”