Gardner syndrome is a rare, inherited disorder characterized by the uncontrolled growth of abnormal tissues throughout the body. This condition is defined by the presence of multiple growths in the intestines, along with tumors and cysts that develop in the skin, soft tissues, and bones. The disorder is a serious hereditary condition because the growths in the colon carry an exceptionally high risk of becoming cancerous. Understanding this syndrome is important for managing its symptoms and mitigating significant health risks.
Defining Gardner Syndrome and its Cause
Gardner syndrome is recognized as a phenotypic variant of Familial Adenomatous Polyposis (FAP). While FAP primarily involves the growth of adenomatous polyps in the colon, Gardner syndrome is distinguished by characteristic manifestations outside of the digestive tract. This condition follows an autosomal dominant inheritance pattern, meaning an affected individual has a 50% chance of passing the gene mutation on to each child.
The underlying cause is a mutation in the Adenomatous Polyposis Coli (APC) gene, located on chromosome 5q22. The APC gene normally acts as a tumor suppressor, regulating cell growth and division. When this gene is altered, its protective function is lost, allowing cells to multiply uncontrollably. This leads to the formation of tumors and abnormal growths throughout the body. The specific location of the mutation on the APC gene can influence the severity and type of extracolonic symptoms a patient experiences.
Primary Manifestations: The Colorectal Risk
The most significant manifestation of Gardner syndrome is the development of hundreds to thousands of adenomatous polyps that line the inner walls of the colon and rectum. These growths often begin to appear around puberty, with the average age of onset being approximately 16 years old. By age 35, nearly 95% of individuals with the syndrome will have developed these intestinal polyps.
These polyps are initially benign, but they possess a nearly 100% lifetime risk of transforming into colorectal cancer if untreated. This malignant progression commonly occurs between the ages of 30 and 50. The average age at which colorectal cancer is detected in patients with this syndrome is around 39 years. Due to the high volume of polyps, often described as having a “dense carpet-like appearance,” prophylactic removal of the colon is necessary for long-term survival.
Symptoms Beyond the Gut
A distinguishing feature of Gardner syndrome is the presence of abnormal growths, referred to as extracolonic manifestations, that occur outside of the gastrointestinal tract.
Osteomas and Cysts
One of the most common non-intestinal features is the formation of osteomas, which are benign bone growths frequently found in the mandible, skull, and long bones. These bony tumors can sometimes appear before the development of colon polyps and may be detectable on dental X-rays. The skin is also commonly affected by multiple epidermoid cysts, which are small, firm bumps located beneath the skin. Unlike common cysts, those associated with Gardner syndrome often appear at an earlier age and in less typical locations like the trunk or scalp.
Desmoid Tumors and Other Findings
Another serious extracolonic growth is the desmoid tumor, a type of locally aggressive soft tissue tumor that forms in connective tissue. While these tumors are noncancerous, they can cause significant problems by growing quickly and compressing nearby organs. Other findings may include dental abnormalities like extra or unerupted teeth, as well as pigmented lesions in the retina known as congenital hypertrophy of the retinal pigment epithelium.
Identifying and Managing the Condition
Diagnosis
Diagnosis of Gardner syndrome is based on the clinical presentation of multiple colonic polyps combined with characteristic extracolonic features. Genetic testing confirms the diagnosis by identifying a pathogenic mutation in the APC gene. For individuals with a known family history, testing may be conducted in childhood to determine the risk and guide preventative care.
Management and Surveillance
Management of the syndrome centers on aggressive surveillance and cancer prevention. Screening with a colonoscopy or sigmoidoscopy is initiated early, often between the ages of 10 and 12, and performed annually or biannually to monitor polyp burden. The definitive treatment to eliminate the near 100% risk of colorectal cancer is prophylactic colectomy, the surgical removal of the colon. This procedure is recommended when the number of polyps becomes too high or difficult to manage.
After the colon is removed, patients require lifelong surveillance for polyps in the remaining upper gastrointestinal tract and for extracolonic growths. Monitoring for desmoid tumors is important due to their aggressive nature, often involving regular imaging scans. Treatment for desmoid tumors ranges from active surveillance to systemic therapies, such as non-steroidal anti-inflammatory drugs or chemotherapy, depending on the tumor’s size and location. Symptomatic osteomas and cysts may also be surgically removed if they cause functional issues or discomfort.