RESEARCH STARTER

Hereditary polyposis syndromes

Hereditary polyposis syndromes are a group of genetic disorders characterized by the development of numerous polyps in the gastrointestinal tract, particularly the small and large intestines. Key syndromes include Familial Adenomatous Polyposis (FAP), Gardner syndrome, Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), and hereditary mixed polyposis syndrome. These conditions often lead to a high risk of colorectal cancer, with FAP resulting in malignant transformation of polyps in nearly all cases if untreated. Symptoms may be absent initially but can include gastrointestinal bleeding, abdominal pain, and changes in bowel habits as polyps grow. Genetic mutations underlie these syndromes, with specific genes linked to each type, and inheritance follows an autosomal dominant pattern, meaning a child has a 50% chance of inheriting the condition if a parent is affected. Early detection through genetic testing and regular screening is vital, as the presence of polyps necessitates intervention, often surgical, to reduce cancer risk. Overall, management of these syndromes requires a multidisciplinary approach, including genetic counseling and regular surveillance to monitor and address any developing health issues.

Full Article

ALSO KNOWN AS: Familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, juvenile polyposis syndrome, Gardner syndrome, hereditary mixed polyposis syndrome, hamartomas, adenomas

RELATED CONDITIONS: Colorectal cancer, bowel obstruction, rectal bleeding, desmoid tumors, osteomas, soft-tissue tumors, pigmented lesions, intestinal polyps, Lynch syndrome

DEFINITION: Hereditary polyposis syndromes are several disorders caused by a genetic predisposition (germline pathogenic variants) for the growth of large numbers of polyps in the small and large intestine—familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), Gardner syndrome, Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), polymerase proofreading-associated polyposis (PPAP), MYH-associated polyposis (MAP), and hereditary mixed polyposis syndrome.

Between 50 and 70 percent of individuals diagnosed with FAP or AFAP have an APC (adenomatous polyposis coli) gene alteration on chromosome 5q21 and are likely to develop many (more than one hundred) intestinal polyps.

Gardner syndrome is a variant of FAP that causes intestinal polyps, skin and soft-tissue tumors, desmoid tumors, and multiple osteomas. Intestinal polyps have a high risk of becoming malignant. This condition can begin in puberty, but the average age for diagnosis is twenty-five, and the average age of diagnosis of malignancy is thirty-nine. Nonmalignant soft-tissue growths and osteomas can appear earlier.

An STK11 (LKB1) mutation causes PJS and produces multiple polyp-like growths called hamartomas that grow in the small intestine rather than the large intestine. They have a low potential for becoming malignant, but can become quite large and cause symptoms requiring surgery.

JPS is a rare childhood-onset, autosomal dominant disease. It produces hamartomatous polyposis rather than adenomatous polyposis.

Hereditary mixed polyposis syndrome, a rare syndrome seen in families, causes a variety of colon polyp types.

Polyps are initially benign but can easily become malignant because of the genetic abnormalities. The term adenomatous polyp refers to a nonmalignant polyp with a high predisposition to become malignant.

Risk factors: Most hereditary polyposis syndromes involve an autosomal dominant genetic error—if one parent carries the genetic mutation, there is a 50 percent chance their child will have the disease regardless of the child's sex. Unlike FAP and PJS, MUTYH-associated polyposis (MAP) is an autosomal recessive syndrome. Although genetic alterations can occur for unknown reasons, people without the mutated gene have a minimal chance of randomly developing one of these syndromes. They cannot transfer it to their offspring. Familial adenomatous polyposis (FAP) and its variant, Gardner syndrome, involve an error in the gene APC on chromosome 5, which is autosomal dominant. The gene responsible for PJS is STK11/LKB1. Two genes, BMPR1A or SMAD4, have been identified as causing JPS. Hereditary mixed polyposis syndrome arises from a gene error on chromosome 15. GREM1 gene mutations, common among individuals of Ashkenazi Jewish ancestry, increase the chance of developing colon polyps or colorectal cancer. Other gene mutations that increase an individual's risk include POLD1, POLE, MSH3, NTHL1, and RNF43.

Etiology and the disease process: Polyps can develop at any age, but those caused by FAP rarely occur before age ten, and JPS is very rare. The chromosome abnormalities in hereditary polyposis syndromes are responsible for cellular changes in the intestine's mucosal lining that initiate the formation of polyps. The chromosomal abnormality drastically increases the possibility of a polyp becoming malignant. Individuals with FAP and Gardner syndrome will develop multiple polyps, so many that surgical removal of the colon is sometimes the only option. Surveillance and screening are the best methods for the prevention and early detection of intestinal polyps.

Nonfamilial causes of polyps are poorly understood but seem responsible for isolated polyp formation. Some of these polyps will become malignant if left untreated. Colorectal cancer screening without a genetic predisposition for familial polyposis or cancer usually begins at age forty-five.

Incidence: FAP affects around one in 8,500 people per year. It is more common in industrialized nations. A person with a family history of adenomatous polyps has a 15 to 20 percent risk of developing polyps and is at a much higher risk of developing colorectal cancer. Without intervention, 95 percent of those with classic FAP develop colorectal polyps by age thirty-five, and 90 percent of these individuals develop colorectal cancer by age fifty. JPS impacts between one in 16,000 and one in 160,000 individuals each year.

Gardner syndrome occurs in approximately one in 7000 to one in 30,000 births. There is an almost 100 percent chance that polyps due to this syndrome will become malignant. PJS occurs in between one in 25,000 and one in 300,000 births annually.

Symptoms: Patients with familial adenomatous polyposis initially do not exhibit symptoms. However, polyps can cause blood to be passed in the stool, which can be detected by a fecal occult blood test (FOBT) or a fecal immunochemical test (FIT). As polyps get larger, patients experience symptoms such as diarrhea, constipation, and abdominal pain. Gardner syndrome causes osteomas, or bone tumors, in the jaw, skull, and teeth. Epidermoid cysts can be present on the face, scalp, arms, and legs. JPS can cause diarrhea, constipation, gastrointestinal hemorrhage, and protein-losing abnormalities.

Screening and diagnosis: People with a family history of polyps should have genetic testing to see if they are carriers of hereditary polyposis syndromes. Their primary relatives (parents, siblings, and children) should also receive genetic testing. If genetic testing is positive, earlier colorectal cancer screening is indicated.

Symptoms of hereditary polyposis syndromes, such as fecal blood or gastrointestinal problems, indicate the need for diagnostic tests such as sigmoidoscopy, colonoscopy, and capsule endoscopy. These tests can find polyps, but only a colonoscopy facilitates a biopsy. Biopsies determine the tissue type—adenomatous, hamartomatous, or cancerous. In cases of FAP, more than one hundred polyps can be present, making total polyp removal impossible. Gardner syndrome can also be diagnosed by the presence of osteomas, bone tumors (usually in the jaw, skull, and teeth), and epidermoid cysts.

Treatment and therapy: Patients with familial adenomatous polyposis often have so many polyps that individual polyp removal during colonoscopy is not an option. In these cases, surgical removal of part or all of the large intestine and the rectum is the main treatment. In a colectomy with ileorectal anastomosis (IRA), the entire colon is removed. The last part of the small intestine (ileum) is attached (anastomosed) to the top of the rectum. Total proctocolectomy with permanent ileostomy involves the removal of the entire colon, rectum, and anus. A small opening is made through the abdominal wall (ostomy), where a bag can be attached to collect fecal material.

The rationale for these seemingly radical procedures is that there is no way to prevent the formation of numerous polyps that are highly likely to become malignant. Removing the colon prevents the formation of adenomatous polyps, lowers the chance of developing colorectal cancer, and saves lives.

Recovery from colectomy takes approximately six to eight weeks. Patients may have to avoid certain foods that upset the bowel, adapt to more frequent bowel movements, and find out what foods and drinks work best for them. Adjusting to a colostomy can be difficult and life-altering. Issues related to self-image, general well-being, and sexuality must be addressed. Counseling and family support are important components of physical and mental health.

Epidermoid cysts and osteomas from Gardner syndrome can be removed if painful or disfiguring, but they are unlikely to become malignant.

In PJS and JPS, the polyps are hamartomas, which usually appear in the small intestine and are fewer in number. Individual polyps can be removed if the patient develops symptoms and there is a chance of obstruction.

Prognosis, prevention, and outcomes: Individuals with the gene alteration that causes hereditary polyposis syndrome should see specialists in gastroenterology and genetics who can manage routine health, screening, and illness when indicated. According to their doctor's guidelines, patients with Gardner syndrome should regularly have a fecal occult blood test (FOBT), sigmoidoscopy or colonoscopy, and upper gastrointestinal tract testing.

There is some evidence that a class of drugs called COX-2 (cyclooxygenase-2) inhibitors, such as sulindac or celecoxib, can prevent the growth of some intestinal polyps and limit the size of those that do form. However, this does not mean COX-2 inhibitors are effective for those with hereditary polyposis syndromes.

Surgical removal of the colon (proctocolectomy with ileostomy, restorative proctocolectomy, or colectomy with or without ileorectal anastomosis) alters patients’ lifestyles but can be lifesaving. Routine medical visits are still necessary, but the surgery significantly reduces the risk of developing colorectal cancer.


Bibliography

Boardman, Lisa A. Intestinal Polyposis Syndromes: Diagnosis and Management. Springer, 2016.

Cheifetz, Adam S., et al. Oxford American Handbook of Gastroenterology and Hepatology. Oxford UP, 2011.

Corso, Giovanni, and Franco Roviello. Spotlight on Familial and Hereditary Gastric Cancer. Springer, 2013.

Das, Prasenjit, et al. Surgical Pathology of the Gastrointestinal System. Volume 1, Gastrointestinal Tract. Springer, 2023.

"Familial Adenomatous Polyposis." Medline Plus, 26 Aug. 2025, medlineplus.gov/genetics/condition/familial-adenomatous-polyposis. Accessed 25 Nov. 2025.

"Familial Adenomatous Polyposis." National Library of Medicine, 5 May 2024, www.ncbi.nlm.nih.gov/books/NBK538233. Accessed 25 Nov. 2025.

Fisher, Stephen. Colon Cancer and the Polyps Connection. Fisher, 1995.

"Gastrointestinal Polyposis Syndromes." Yale Medicine, www.yalemedicine.org/conditions/gastrointestinal-polyposis-syndromes. Accessed 25 Nov. 2025.

"Hereditary Colon Polyposis." Memorial Sloan Kettering Cancer Center, www.mskcc.org/cancer-care/risk-assessment-screening/genetic-counseling-and-testing/hereditary-cancer-genes-and-hereditary-cancer-syndromes/hereditary-colon-cancer-and-polyposis. Accessed 25 Nov. 2025.

Joo, Jihoon E., et al. “Genetics, Genomics and Clinical Features of Adenomatous Polyposis.” Familial Cancer, vol. 24, no. 2, 2025, p. 38, doi:10.1007/s10689-025-00460-0. Accessed 25 Nov. 2025.

"Update on Hereditary Gastrointestinal Cancers: Lynch Syndrome and Familial Adenomatous Polyposis Syndromes." Mayo Clinic, 2020, www.mayoclinic.org/medical-professionals/digestive-diseases/news/update-on-hereditary-gastrointestinal-cancers-lynch-syndrome-and-familial-adenomatous-polyposis-syndromes/mac-20479629. Accessed 25 Nov. 2025.

Full Article

ALSO KNOWN AS: Familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, juvenile polyposis syndrome, Gardner syndrome, hereditary mixed polyposis syndrome, hamartomas, adenomas

RELATED CONDITIONS: Colorectal cancer, bowel obstruction, rectal bleeding, desmoid tumors, osteomas, soft-tissue tumors, pigmented lesions, intestinal polyps, Lynch syndrome

DEFINITION: Hereditary polyposis syndromes are several disorders caused by a genetic predisposition (germline pathogenic variants) for the growth of large numbers of polyps in the small and large intestine—familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), Gardner syndrome, Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), polymerase proofreading-associated polyposis (PPAP), MYH-associated polyposis (MAP), and hereditary mixed polyposis syndrome.

Between 50 and 70 percent of individuals diagnosed with FAP or AFAP have an APC (adenomatous polyposis coli) gene alteration on chromosome 5q21 and are likely to develop many (more than one hundred) intestinal polyps.

Gardner syndrome is a variant of FAP that causes intestinal polyps, skin and soft-tissue tumors, desmoid tumors, and multiple osteomas. Intestinal polyps have a high risk of becoming malignant. This condition can begin in puberty, but the average age for diagnosis is twenty-five, and the average age of diagnosis of malignancy is thirty-nine. Nonmalignant soft-tissue growths and osteomas can appear earlier.

An STK11 (LKB1) mutation causes PJS and produces multiple polyp-like growths called hamartomas that grow in the small intestine rather than the large intestine. They have a low potential for becoming malignant, but can become quite large and cause symptoms requiring surgery.

JPS is a rare childhood-onset, autosomal dominant disease. It produces hamartomatous polyposis rather than adenomatous polyposis.

Hereditary mixed polyposis syndrome, a rare syndrome seen in families, causes a variety of colon polyp types.

Polyps are initially benign but can easily become malignant because of the genetic abnormalities. The term adenomatous polyp refers to a nonmalignant polyp with a high predisposition to become malignant.

Risk factors: Most hereditary polyposis syndromes involve an autosomal dominant genetic error—if one parent carries the genetic mutation, there is a 50 percent chance their child will have the disease regardless of the child's sex. Unlike FAP and PJS, MUTYH-associated polyposis (MAP) is an autosomal recessive syndrome. Although genetic alterations can occur for unknown reasons, people without the mutated gene have a minimal chance of randomly developing one of these syndromes. They cannot transfer it to their offspring. Familial adenomatous polyposis (FAP) and its variant, Gardner syndrome, involve an error in the gene APC on chromosome 5, which is autosomal dominant. The gene responsible for PJS is STK11/LKB1. Two genes, BMPR1A or SMAD4, have been identified as causing JPS. Hereditary mixed polyposis syndrome arises from a gene error on chromosome 15. GREM1 gene mutations, common among individuals of Ashkenazi Jewish ancestry, increase the chance of developing colon polyps or colorectal cancer. Other gene mutations that increase an individual's risk include POLD1, POLE, MSH3, NTHL1, and RNF43.

Etiology and the disease process: Polyps can develop at any age, but those caused by FAP rarely occur before age ten, and JPS is very rare. The chromosome abnormalities in hereditary polyposis syndromes are responsible for cellular changes in the intestine's mucosal lining that initiate the formation of polyps. The chromosomal abnormality drastically increases the possibility of a polyp becoming malignant. Individuals with FAP and Gardner syndrome will develop multiple polyps, so many that surgical removal of the colon is sometimes the only option. Surveillance and screening are the best methods for the prevention and early detection of intestinal polyps.

Nonfamilial causes of polyps are poorly understood but seem responsible for isolated polyp formation. Some of these polyps will become malignant if left untreated. Colorectal cancer screening without a genetic predisposition for familial polyposis or cancer usually begins at age forty-five.

Incidence: FAP affects around one in 8,500 people per year. It is more common in industrialized nations. A person with a family history of adenomatous polyps has a 15 to 20 percent risk of developing polyps and is at a much higher risk of developing colorectal cancer. Without intervention, 95 percent of those with classic FAP develop colorectal polyps by age thirty-five, and 90 percent of these individuals develop colorectal cancer by age fifty. JPS impacts between one in 16,000 and one in 160,000 individuals each year.

Gardner syndrome occurs in approximately one in 7000 to one in 30,000 births. There is an almost 100 percent chance that polyps due to this syndrome will become malignant. PJS occurs in between one in 25,000 and one in 300,000 births annually.

Symptoms: Patients with familial adenomatous polyposis initially do not exhibit symptoms. However, polyps can cause blood to be passed in the stool, which can be detected by a fecal occult blood test (FOBT) or a fecal immunochemical test (FIT). As polyps get larger, patients experience symptoms such as diarrhea, constipation, and abdominal pain. Gardner syndrome causes osteomas, or bone tumors, in the jaw, skull, and teeth. Epidermoid cysts can be present on the face, scalp, arms, and legs. JPS can cause diarrhea, constipation, gastrointestinal hemorrhage, and protein-losing abnormalities.

Screening and diagnosis: People with a family history of polyps should have genetic testing to see if they are carriers of hereditary polyposis syndromes. Their primary relatives (parents, siblings, and children) should also receive genetic testing. If genetic testing is positive, earlier colorectal cancer screening is indicated.

Symptoms of hereditary polyposis syndromes, such as fecal blood or gastrointestinal problems, indicate the need for diagnostic tests such as sigmoidoscopy, colonoscopy, and capsule endoscopy. These tests can find polyps, but only a colonoscopy facilitates a biopsy. Biopsies determine the tissue type—adenomatous, hamartomatous, or cancerous. In cases of FAP, more than one hundred polyps can be present, making total polyp removal impossible. Gardner syndrome can also be diagnosed by the presence of osteomas, bone tumors (usually in the jaw, skull, and teeth), and epidermoid cysts.

Treatment and therapy: Patients with familial adenomatous polyposis often have so many polyps that individual polyp removal during colonoscopy is not an option. In these cases, surgical removal of part or all of the large intestine and the rectum is the main treatment. In a colectomy with ileorectal anastomosis (IRA), the entire colon is removed. The last part of the small intestine (ileum) is attached (anastomosed) to the top of the rectum. Total proctocolectomy with permanent ileostomy involves the removal of the entire colon, rectum, and anus. A small opening is made through the abdominal wall (ostomy), where a bag can be attached to collect fecal material.

The rationale for these seemingly radical procedures is that there is no way to prevent the formation of numerous polyps that are highly likely to become malignant. Removing the colon prevents the formation of adenomatous polyps, lowers the chance of developing colorectal cancer, and saves lives.

Recovery from colectomy takes approximately six to eight weeks. Patients may have to avoid certain foods that upset the bowel, adapt to more frequent bowel movements, and find out what foods and drinks work best for them. Adjusting to a colostomy can be difficult and life-altering. Issues related to self-image, general well-being, and sexuality must be addressed. Counseling and family support are important components of physical and mental health.

Epidermoid cysts and osteomas from Gardner syndrome can be removed if painful or disfiguring, but they are unlikely to become malignant.

In PJS and JPS, the polyps are hamartomas, which usually appear in the small intestine and are fewer in number. Individual polyps can be removed if the patient develops symptoms and there is a chance of obstruction.

Prognosis, prevention, and outcomes: Individuals with the gene alteration that causes hereditary polyposis syndrome should see specialists in gastroenterology and genetics who can manage routine health, screening, and illness when indicated. According to their doctor's guidelines, patients with Gardner syndrome should regularly have a fecal occult blood test (FOBT), sigmoidoscopy or colonoscopy, and upper gastrointestinal tract testing.

There is some evidence that a class of drugs called COX-2 (cyclooxygenase-2) inhibitors, such as sulindac or celecoxib, can prevent the growth of some intestinal polyps and limit the size of those that do form. However, this does not mean COX-2 inhibitors are effective for those with hereditary polyposis syndromes.

Surgical removal of the colon (proctocolectomy with ileostomy, restorative proctocolectomy, or colectomy with or without ileorectal anastomosis) alters patients’ lifestyles but can be lifesaving. Routine medical visits are still necessary, but the surgery significantly reduces the risk of developing colorectal cancer.


Bibliography

Boardman, Lisa A. Intestinal Polyposis Syndromes: Diagnosis and Management. Springer, 2016.

Cheifetz, Adam S., et al. Oxford American Handbook of Gastroenterology and Hepatology. Oxford UP, 2011.

Corso, Giovanni, and Franco Roviello. Spotlight on Familial and Hereditary Gastric Cancer. Springer, 2013.

Das, Prasenjit, et al. Surgical Pathology of the Gastrointestinal System. Volume 1, Gastrointestinal Tract. Springer, 2023.

"Familial Adenomatous Polyposis." Medline Plus, 26 Aug. 2025, medlineplus.gov/genetics/condition/familial-adenomatous-polyposis. Accessed 25 Nov. 2025.

"Familial Adenomatous Polyposis." National Library of Medicine, 5 May 2024, www.ncbi.nlm.nih.gov/books/NBK538233. Accessed 25 Nov. 2025.

Fisher, Stephen. Colon Cancer and the Polyps Connection. Fisher, 1995.

"Gastrointestinal Polyposis Syndromes." Yale Medicine, www.yalemedicine.org/conditions/gastrointestinal-polyposis-syndromes. Accessed 25 Nov. 2025.

"Hereditary Colon Polyposis." Memorial Sloan Kettering Cancer Center, www.mskcc.org/cancer-care/risk-assessment-screening/genetic-counseling-and-testing/hereditary-cancer-genes-and-hereditary-cancer-syndromes/hereditary-colon-cancer-and-polyposis. Accessed 25 Nov. 2025.

Joo, Jihoon E., et al. “Genetics, Genomics and Clinical Features of Adenomatous Polyposis.” Familial Cancer, vol. 24, no. 2, 2025, p. 38, doi:10.1007/s10689-025-00460-0. Accessed 25 Nov. 2025.

"Update on Hereditary Gastrointestinal Cancers: Lynch Syndrome and Familial Adenomatous Polyposis Syndromes." Mayo Clinic, 2020, www.mayoclinic.org/medical-professionals/digestive-diseases/news/update-on-hereditary-gastrointestinal-cancers-lynch-syndrome-and-familial-adenomatous-polyposis-syndromes/mac-20479629. Accessed 25 Nov. 2025.

More Like ThisRelated Articles

Related Articles (4)

Related Articles (4)