What is the management and treatment of Gardner syndrome?

Management and Treatment of Gardner Syndrome

Gardner syndrome requires prophylactic colectomy as the definitive treatment to prevent inevitable colorectal cancer, combined with lifelong surveillance for extracolonic manifestations including desmoid tumors, duodenal polyps, and osteomas. 1

Initial Diagnostic Workup

Genetic Testing

• Perform APC gene mutation testing first, which detects mutations in approximately 80% of patients with numerous adenomas 1
• If APC testing is negative, proceed to MUTYH gene testing, as MUTYH-associated polyposis follows autosomal recessive inheritance 1
• The position of the APC mutation correlates with disease severity and extracolonic manifestations, influencing surgical decisions 1

Endoscopic Evaluation

• Complete colonoscopy is mandatory to assess the full extent of colorectal polyposis 1
• Duodenoscopy is essential for surveillance given the high frequency of duodenal involvement 2

Extracolonic Assessment

• Evaluate for key clinical features: osteomas (skull, mandible, paranasal sinuses), epidermoid cysts, desmoid tumors, and dental abnormalities including supernumerary teeth 1, 3
• Conduct ophthalmologic examination for retinal epithelial abnormalities that help distinguish Gardner syndrome from other polyposis syndromes 4

Colorectal Management

Screening Timeline

• Begin colorectal screening at age 10-12 years due to the 100% lifetime risk of colorectal cancer 1, 2
• Perform flexible sigmoidoscopy every 2 years, which is adequate given the universal distribution of adenomas 1

Surgical Intervention

• Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) with mucosectomy is the preferred surgical procedure, as it eliminates all colorectal mucosa without requiring a permanent ostomy 4, 5
• Timing of surgery should consider the patient's age, polyp burden, and family history of early colorectal cancer 1
• Prophylactic colectomy is the only effective treatment to prevent colorectal cancer progression 2, 5

Management of Extracolonic Manifestations

Desmoid Tumors

Desmoid tumors occur in 7.5-16% of FAP patients and represent a significant cause of morbidity and mortality after colectomy 1, 5

First-line approach: Active surveillance with regular MRI scans and clinical review 1

Medical therapy options when intervention is needed:

• Sorafenib 1
• Pegylated liposomal doxorubicin 1
• Pazopanib 1
• Low-dose chemotherapy including oral vinorelbine 1
• Nirogacestat (γ-Secretase Inhibitor) has demonstrated benefit in progression-free survival and symptom control 1

Risk factors for desmoid tumor development:

• Positive family history 1
• Previous abdominal surgery 1
• Specific APC mutation sites 1
• Young age and male gender 1

Osteomas and Soft Tissue Tumors

• Surgical excision is indicated for symptomatic osteomas causing functional or aesthetic concerns 2, 6
• Epidermoid cysts can be excised based on location, size, and number 2, 4
• Osteomas primarily affect facial eumorphy and temporomandibular joint function but rarely undergo malignant transformation 6

Lifelong Surveillance Protocol

Post-Colectomy Monitoring

• Rectal polyp surveillance: Lifelong endoscopic monitoring if rectum is preserved 1
• Duodenal and periampullary surveillance: Frequent endoscopy to prevent periampullary carcinoma, a significant cause of mortality after colectomy 1, 5
• Desmoid tumor monitoring: Regular clinical and MRI surveillance, as there is no definitive treatment available 1, 5

Surveillance Intervals

• Clinical reassessment every 3-6 months to evaluate disease progression, symptom burden, and functional impairment 7
• MRI provides superior characterization for monitoring extracolonic manifestations 7

Genetic Counseling and Family Screening

Inheritance Pattern

• Autosomal dominant with almost complete penetrance (80%) 6
• Each child of an affected parent has a 50% chance of inheriting the predisposition 1
• One-third to half of new FAP cases represent de novo mutations with no family history 1

Family Management

• Genetic testing of family members allows for targeted surveillance of only mutation carriers 1
• Screen at-risk family members starting at age 10-12 years 1

Critical Pitfalls to Avoid

• Do not delay colectomy once polyposis is confirmed, as colorectal cancer risk is 100% 2, 5
• Do not neglect duodenal surveillance after colectomy, as periampullary carcinoma becomes a leading cause of death 5
• Do not perform aggressive surgery for desmoid tumors initially, as active surveillance is first-line given their unpredictable natural history with potential for spontaneous regression 1
• Do not assume negative family history excludes diagnosis, as up to half of cases are de novo mutations 1