Gardner syndrome is a rare, inherited disorder and a specific clinical variant of Familial Adenomatous Polyposis (FAP). It is characterized by numerous growths within the colon and benign tumors in various tissues outside the digestive tract. Because these abnormal growths carry a nearly 100% lifetime risk of developing into colorectal cancer, early identification is important for effective management.
Defining Gardner Syndrome and its Genetic Basis
Gardner syndrome is caused by a mutation in the Adenomatous Polyposis Coli (APC) gene, located on chromosome 5. The APC gene normally acts as a tumor suppressor, controlling how quickly cells grow and divide. When mutated, its function is lost, leading to uncontrolled cell proliferation and the formation of tumors and polyps.
The disorder follows an autosomal dominant inheritance pattern. A person only needs to inherit one copy of the mutated APC gene to develop the syndrome, resulting in a 50% chance of passing the condition on to each child. While most cases are inherited, approximately 20% of diagnoses result from a spontaneous mutation in the APC gene in a person with no family history.
Gastrointestinal Manifestations
The most serious health concern is the development of numerous adenomatous polyps throughout the colon and rectum. These growths, initially non-cancerous, typically begin forming around puberty, with diagnosis often occurring in the early twenties. Individuals often develop hundreds, and sometimes thousands, of these polyps, sometimes carpeting the inner lining of the large intestine.
The lifetime risk of developing colorectal cancer approaches 100% if the colon is not surgically removed. Malignant transformation typically occurs by the age of 40 to 50 years in untreated patients. Polyps can also appear in the upper gastrointestinal tract, including the stomach and duodenum. These upper GI polyps, especially those near the ampulla of Vater, also carry a risk of malignant change and require careful surveillance.
Extracolonic Features
One of the most common extracolonic features is the development of osteomas, which are benign growths of bone tissue. These are frequently found in the skull, mandible, or jaw, and their appearance can often precede the formation of colonic polyps, serving as an early diagnostic clue.
Another significant manifestation is the desmoid tumor, an aggressive fibrous growth often found in the abdominal wall or mesentery. Although histologically benign, desmoid tumors can be locally aggressive and cause substantial morbidity by compressing or damaging internal organs, sometimes becoming life-threatening. Patients also frequently develop skin and dental abnormalities. Skin issues include multiple epidermoid cysts (small bumps under the skin). Dental issues are common and can involve supernumerary (extra) teeth, impacted teeth, or odontomas.
Diagnosis and Management
Diagnosis is confirmed through clinical findings, endoscopic evaluation, and genetic testing. A colonoscopy is mandated to assess the extent of the adenomatous polyposis, often revealing hundreds of polyps. Genetic testing involves sequencing the APC gene to identify the specific mutation, confirming the diagnosis and helping predict disease severity.
The primary management strategy focuses on preventing progression to colorectal cancer. This requires a prophylactic colectomy, or surgical removal of the colon, which is the only effective way to eliminate cancer risk. The preferred surgery is often a restorative proctocolectomy with an ileal pouch-anal anastomosis, removing the entire colon and rectum while preserving bowel function.
Long-term care involves lifelong surveillance for extracolonic manifestations and upper GI polyps. This includes regular endoscopies to monitor the duodenum and stomach for adenomas. Desmoid tumors are monitored with regular imaging, such as MRI, and may be treated medically if they grow aggressively. Regular checks with a dentist and dermatologist are also necessary.