Gardner's syndrome

Overview

Gardner's syndrome is a rare genetic disorder that is considered a variant of familial adenomatous polyposis (FAP). It is characterized by the development of numerous colorectal polyps and a high risk of colorectal cancer, along with various non-cancerous tumors and growths in other parts of the body. These may include osteomas (bony growths), epidermoid cysts, dental abnormalities, and desmoid tumors. Without proper medical intervention, nearly all individuals with Gardner's syndrome will develop colorectal cancer, often by the age of 40.

Causes

Gardner's syndrome is caused by mutations in the APC (Adenomatous Polyposis Coli) gene located on chromosome 5q21. The APC gene is a tumor suppressor gene responsible for regulating cell growth and apoptosis. Mutations in this gene lead to uncontrolled cell division, particularly in the colon and rectum. The syndrome is inherited in an autosomal dominant pattern, meaning that only one copy of the mutated gene from an affected parent is sufficient to pass the condition to offspring.

Symptoms

The symptoms of Gardner’s syndrome can vary widely but typically appear in adolescence or early adulthood. Common features include:

• Colorectal polyps: Hundreds to thousands of polyps develop in the colon and rectum, with high risk of malignant transformation

• Osteomas: Benign bony tumors, especially in the skull and jaw

• Epidermoid cysts: Noncancerous skin cysts, often on the scalp, face, or back

• Dental abnormalities: Impacted teeth, extra (supernumerary) teeth, or jaw cysts

• Desmoid tumors: Fibrous tumors that may occur in the abdomen or other soft tissues

• Retinal lesions: Congenital hypertrophy of the retinal pigment epithelium (CHRPE)

If left untreated, the progression to colorectal cancer is nearly inevitable by middle age.

Diagnosis

Diagnosing Gardner’s syndrome involves a combination of clinical assessment, family history, imaging, and genetic testing:

• Colonoscopy: To identify and assess the number and size of colorectal polyps

• Genetic testing: Identification of mutations in the APC gene confirms the diagnosis

• Imaging studies: X-rays or CT scans to detect osteomas and desmoid tumors

• Ophthalmologic examination: To detect CHRPE in the retina

• Dental X-rays: Reveal supernumerary teeth or jaw anomalies

• Family history evaluation: Identification of affected relatives can support early diagnosis in at-risk individuals

Treatment

Treatment of Gardner’s syndrome focuses on preventing cancer and managing extra-colonic manifestations:

• Prophylactic colectomy: Surgical removal of the colon is often recommended once polyps are numerous or dysplastic

• Regular screening: Surveillance of the gastrointestinal tract, thyroid, and other at-risk organs

• Desmoid tumor management: May involve surgery, anti-inflammatory drugs, chemotherapy, or radiation depending on size and location

• Dermatologic and dental care: Management of cysts, osteomas, and dental issues to improve quality of life

• Genetic counseling: For affected families and individuals considering children

Surveillance of at-risk family members is essential, even before the onset of symptoms.

Prognosis

The prognosis of Gardner’s syndrome depends heavily on early diagnosis and proactive treatment. Without preventive colectomy, the risk of developing colorectal cancer approaches 100% by age 40–50. However, with regular screening and appropriate surgical intervention, life expectancy can be significantly extended. Management of extracolonic manifestations, particularly aggressive desmoid tumors, may still pose challenges. Long-term follow-up with a multidisciplinary team is essential to ensure optimal outcomes and cancer prevention.