What is the management and treatment of Gardner's syndrome?

Gardner Syndrome Management

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 other malignancies. 1

Diagnosis and Genetic Testing

• Gardner syndrome is a variant of Familial Adenomatous Polyposis (FAP) caused by germline APC gene mutations with autosomal dominant inheritance, presenting with colorectal adenomatous polyps plus extracolonic manifestations (osteomas, epidermoid cysts, desmoid tumors, soft tissue tumors) 1, 2
• Genetic testing for APC mutations detects approximately 80% of patients with numerous adenomas 1
• If APC testing is negative, perform MUTYH gene testing, as MUTYH-associated polyposis follows autosomal recessive inheritance 1
• Complete colonoscopy is essential to assess the extent of colorectal polyposis 1
• Key clinical features to evaluate include colorectal polyps, desmoid tumors, dental abnormalities (supernumerary teeth), osteomas, and retinal abnormalities 1, 2

Colorectal Screening and Surveillance

• Begin colorectal screening at age 10-12 years due to high risk of early-onset colorectal cancer 1, 3
• Flexible sigmoidoscopy every 2 years is adequate given the universal distribution of adenomas 1
• Without surgical intervention, patients develop colorectal cancer by mean age 40-50 years with nearly 100% risk 3, 4
• Colorectal cancer before age 10 is extremely rare, with incidental cases between ages 11-15 3

Surgical Management

The preferred surgical approach is restorative proctocolectomy with ileal pouch anal anastomosis (RPC/IPAA) with mucosectomy, as this eliminates all colorectal mucosa without requiring a permanent ostomy 2, 5

Surgical Decision Factors:

• The position of the APC mutation influences surgical decisions and correlates with severity of rectal polyposis 1, 3
• Consider patient age, desire for children, desmoid tumor risk, APC mutation site, and severity of rectal polyposis 3
• For classical FAP with diffuse polyp distribution, total proctocolectomy with ileal pouch-anal anastomosis is recommended 3
• For attenuated FAP with predominantly right-sided polyps, colectomy with ileorectal anastomosis may be considered in selected cases 3
• Prophylactic colectomy should be performed when the patient reaches appropriate age (typically early adolescence to early adulthood) 4, 6

Desmoid Tumor Management

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

Risk Factors:

• Positive family history, previous abdominal surgery, and specific APC mutation sites 1
• Young age, male gender, abdominal site, family history of cancer, and absence of CTNNB1 tumor mutation 1

Treatment Approach:

• First-line approach is active surveillance with regular MRI scans and clinical review 1
• Medical therapy options include Sorafenib, Pegylated liposomal doxorubicin, Pazopanib, and low-dose chemotherapy including oral vinorelbine 1
• Nirogacestat (γ-Secretase Inhibitor) has shown benefit in progression-free survival and symptom control 1
• Surgical resection may be considered for symptomatic or enlarging tumors 6

Lifelong Post-Colectomy Surveillance

After colectomy, patients require lifelong surveillance for multiple sites:

• Rectal polyps (if rectum preserved) - regular endoscopic surveillance 1
• Duodenal and periampullary adenomas - frequent endoscopy is essential as periampullary carcinoma is a significant cause of mortality after colectomy 1, 4, 5
• Desmoid tumors - regular MRI scans and clinical review 1
• Thyroid cancer - surveillance for thyroid malignancies 5

Extracolonic Manifestations Management

• Epidermoid cysts and soft tissue tumors: Excision based on location, size, and number of lesions 4, 2
• Osteomas: Monitor for symptomatic lesions affecting skull bones, mandible, and paranasal sinuses 7
• Retinal abnormalities: Periodic ophthalmologic examinations to detect retinal epithelium abnormalities 4, 2

Genetic Counseling

• Each child of an affected parent has 50% chance of inheriting the predisposition 1
• One-third to half of new FAP cases represent de novo mutations with no family history 1
• Genetic testing of family members allows targeted surveillance only for mutation carriers 1
• The position of APC mutations correlates with disease severity and extracolonic manifestations 1, 3

Multidisciplinary Team Approach

A coordinated team involving gastroenterologists, surgeons, geneticists, oncologists, and other specialists is crucial for optimal management 1