Hereditary Mixed Polyposis Syndrome (HMPS) is an uncommon inherited condition defined by the development of various types of polyps within the colon. The term “mixed” refers to the fact that individuals with this syndrome can develop multiple distinct kinds of polyps, which contrasts with other syndromes characterized by one primary polyp type. The condition is passed down through families and can present with symptoms beginning in childhood.
Genetic Causes and Inheritance
The primary genetic factor linked to Hereditary Mixed Polyposis Syndrome involves a change near the GREM1 gene. In most documented cases of HMPS, the cause is not a mutation within the gene itself but rather a duplication of a large segment of DNA located upstream from the gene. This specific genetic alteration, a 40-kilobase duplication, is notably found in some individuals of Ashkenazi Jewish heritage.
This duplication is thought to cause an overproduction of the Gremlin-1 protein, which disrupts normal cellular signaling pathways in the colon. The inheritance pattern for HMPS is autosomal dominant. This means that an individual needs to inherit only one copy of the altered gene from one parent to develop the syndrome. Consequently, a parent with the GREM1 duplication has a 50% chance of passing the genetic change to each of their children.
Signs and Symptoms of HMPS
HMPS involves growths that can include adenomatous polyps, which are composed of cells that line the colon and have the potential to change over time. Another common type is the juvenile polyp, a form of hamartoma, which is a benign, disorganized growth of tissues native to the colon. These are distinct from adenomas and are named for their microscopic appearance, not the age of the individual.
Serrated polyps, including hyperplastic polyps, represent another category found in individuals with HMPS. While some hyperplastic polyps have low potential for transformation, other serrated polyps carry a higher risk. Other general symptoms may arise, such as rectal bleeding or shifts in bowel function, often related to the size and number of the polyps.
The Diagnosis Process
Diagnosing HMPS typically begins when symptoms or a family history prompts a medical evaluation. The initial and most direct diagnostic tool is a colonoscopy. This procedure allows a doctor to visually inspect the entire inner lining of the colon and rectum, identifying the number, size, and location of any polyps. The varied appearance of the polyps seen during a colonoscopy may suggest a mixed polyposis condition.
During the colonoscopy, tissue samples, or biopsies, are taken from the different types of polyps for histopathological analysis by a pathologist. This step is necessary to definitively identify the various polyp types present—such as adenomatous, juvenile, or serrated—which is a requirement for an HMPS diagnosis. To confirm the underlying hereditary cause, genetic testing is often recommended to look for the duplication near the GREM1 gene.
Associated Health Risks
The presence of multiple polyp types in HMPS is associated with a heightened risk of developing colorectal cancer. This increased risk is primarily linked to the adenomatous polyps, which are recognized as precursor lesions to cancer. Over time, the cells within these adenomas can transform into malignant tumors. The progression of some polyps to advanced adenomas can be rapid in some individuals with HMPS.
While the exact lifetime cancer risk is still being studied due to the rarity of the syndrome, it is considered to be moderately increased. Some estimates suggest the lifetime risk of colorectal cancer for individuals with the GREM1 duplication may be between 10% and 25%. Though less common, some research has noted other features like extracolonic tumors in a few families, but the predominant health concern remains colorectal cancer.
Management and Surveillance Strategies
Management of HMPS focuses on proactive surveillance and prevention to mitigate the elevated cancer risk. The primary strategy is regular colonoscopy. Surveillance begins at a younger age than for the general population, often recommended to start between the ages of 25 and 30. The frequency of these screenings is personalized based on the findings; if no polyps are found, a colonoscopy might be repeated every two to three years.
If polyps are detected during a colonoscopy, the surveillance interval is often shortened to every one to two years. A procedure called a polypectomy, which is the removal of the polyps, is performed during the colonoscopy. Removing the polyps, particularly the adenomatous ones, directly addresses the risk of them progressing to cancer. This ongoing cycle of surveillance and polyp removal is the primary method for managing the condition long-term.
In situations where the number of polyps becomes too high to manage effectively through colonoscopy—a high polyp burden—more extensive surgical options may be considered. A colectomy, the surgical removal of all or part of the colon, might be recommended. This is a significant intervention reserved for cases where the risk of cancer is very high or when the polyps are too numerous to be removed endoscopically. The specific management plan is tailored to each individual’s clinical situation and family history.