Hereditary mixed polyposis syndrome and cancer
Hereditary mixed polyposis syndrome (HMPS) is a genetic condition that increases the likelihood of developing various types of polyps in the gastrointestinal tract, particularly in the colon, and is associated with a heightened risk of colorectal cancer. This syndrome is characterized by the presence of multiple polyp types, including atypical juvenile polyps, hyperplastic polyps, and colonic adenomas. It is inherited in a dominant manner, meaning that only one affected gene copy is sufficient to predispose an individual to the condition, resulting in a 50% chance of transmission from an affected parent. The GREM1 gene mutations are identified as the underlying cause of this syndrome.
Symptoms may arise from polyp formation and can include anemia, blood loss, or bowel obstruction. Early detection through regular screening, such as colonoscopies, is crucial for individuals with a family history of HMPS, with recommendations typically starting at age fifteen. Diagnosis is confirmed through the identification of specific polyp types and a detailed family history. While treatment primarily involves the removal of polyps during colonoscopy, the lifetime risk of developing colorectal cancer for individuals with HMPS can be as high as 30%. Understanding the implications of HMPS is vital for prevention and management strategies, particularly for those with a hereditary predisposition.
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Subject Terms
Hereditary mixed polyposis syndrome and cancer
ALSO KNOWN AS: Colorectal adenoma and carcinoma 1 (CRAC1), HMPS
Related condition: Juvenile polyposis
DEFINITION: Hereditary mixed polyposis syndrome is a dominantly inherited condition that predisposes an individual to the development of polyps in the gastrointestinal tract. Patients with this syndrome exhibit multiple polyp types, including atypical juvenile polyps, hyperplastic polyps, colonic adenomas, colonic adenocarcinomas, and polyps that show mixed or hybrid characteristics. The syndrome also predisposes patients to developing colorectal cancer.
Risk factors: Hereditary mixed polyposis syndrome is a genetic disorder transmitted dominantly—only one of the two gene copies must be affected to develop the condition. Therefore, if one parent has the disease, there is a 50 percent chance they will have it.
Etiology and the disease process: Hereditary mixed polyposis syndrome is a genetic disorder caused by mutations in the GREM1 gene. The disease begins with the formation of polyps, or tissue growths originating from a mucous membrane. Although polyps are usually benign, they can develop into tumors if they are not removed.
Symptoms: Symptoms of hereditary mixed polyposis syndrome are associated with polyp formation and can include anemia, blood loss, the passage of bright red, bloody stool, or bowel obstruction.
Incidence: Hereditary mixed polyposis syndrome is a rare disease that has been described in only a few families. The mutation incidence is higher in individuals of Ashkenazi Jewish heritage than in the general population.
Screening and diagnosis: Patients with a family history of hereditary mixed polyposis syndrome should undergo frequent colonoscopy screenings according to their doctor’s guidance. Most recommend bi-annual or tri-annual screenings beginning at age fifteen for individuals with a family history of the disease. Polyps left untreated can develop into cancer. Most colonoscopies find fewer than fifteen polyps in patients with hereditary mixed polyposis syndrome. Diagnosis is made based on multiple types of polyps or polyps with mixed characteristics in histological examination and a family history of the disease.
Treatment and therapy: Colonoscopy with polyp removal is usually sufficient to control the symptoms.
Prognosis, prevention, and outcomes: The median age of diagnosis for hereditary mixed polyposis syndrome is forty years. The median age of cancer diagnosis is forty-seven years. The lifetime risk for developing colorectal cancer is 30 percent. Prevention is based on identifying at-risk individuals based on a family history of hereditary mixed polyposis syndrome.
Bibliography
Das, Prasenjit et al. Surgical Pathology of the Gastrointestinal System. Volume 1, Gastrointestinal Tract. Springer, 2023.
"Familial Adenomatous Polyposis." National Library of Medicine, 5 May 2024, www.ncbi.nlm.nih.gov/books/NBK538233. Accessed 20 June 2024.
Garrett, Friedman, and G Jose. Management of Hereditary Colorectal Cancer: A Multidisciplinary Approach. Springer International Publishing, 2020.
"Gastrointestinal Polyposis Syndromes." Yale Medicine, www.yalemedicine.org/conditions/gastrointestinal-polyposis-syndromes. Accessed 20 June 2024.
Zhao, Zi-Ye, et al. "Re-recognition of BMPR1A-related Polyposis: Beyond Juvenile Polyposis and Hereditary Mixed Polyposis Syndrome." Gastroenterology Report, vol. 11, Jan. 2023, doi.org/10.1093/gastro/goac082.