What is the evaluation and management of Gardner syndrome?

Evaluation and Management of Gardner Syndrome

Gardner syndrome requires comprehensive genetic testing for APC mutations, colonoscopy, and multidisciplinary management to prevent colorectal cancer and manage extracolonic manifestations.

Diagnostic Evaluation

Clinical Assessment

• Gardner syndrome is a variant of Familial Adenomatous Polyposis (FAP) characterized by colorectal adenomatous polyps plus extracolonic manifestations including osteomas, epidermoid cysts, desmoid tumors, and other soft tissue tumors 1
• Key clinical features to assess include:
  • Colorectal polyps (the hallmark feature) 2
  • Osteomas (particularly in the skull, mandible, and maxilla) 3
  • Epidermoid/sebaceous cysts 4
  • Desmoid tumors (aggressive fibromatosis) 2
  • Dental abnormalities (supernumerary teeth) 2
  • Congenital hypertrophy of retinal pigmented epithelium 2

Genetic Testing

• Genetic testing for germline mutations in the APC gene is the gold standard for diagnosis 1
• APC mutations are detected in approximately 80% of patients with numerous adenomas 1
• If no APC mutation is identified, testing for MUTYH mutations should be performed, as MUTYH-associated polyposis (MAP) follows an autosomal recessive inheritance pattern 1
• The position of the APC mutation correlates with disease severity and extracolonic manifestations 1

Imaging and Endoscopy

• Complete colonoscopy is essential to assess the extent of colorectal polyposis 2
• Panoramic radiographs and CBCT imaging are recommended to identify osteomas in the jaw and skull 3
• MRI is indicated for suspected desmoid tumors 2

Management

Colorectal Management

• Prophylactic colectomy is the standard of care for patients with Gardner syndrome due to the 100% risk of colorectal cancer if left untreated 5
• Restorative proctocolectomy with ileal pouch anal anastomosis with mucosectomy is the preferred surgical approach for colonic manifestations 4
• The timing of surgery may be influenced by:
  • Polyp burden and histology 2
  • Patient age 2
  • Family history of early colorectal cancer 2

Management of Desmoid Tumors

• First-line approach for desmoid tumors is active surveillance with regular MRI scans and clinical review 2
• For progressing cases, medical therapy is preferred over surgery except for abdominal wall desmoids, where surgery has lower relapse rates 2
• Medical therapy options include:
  • Sorafenib (shown efficacy in placebo-controlled studies) 2
  • Pegylated liposomal doxorubicin 2
  • Pazopanib 2
  • Low-dose chemotherapy including oral vinorelbine 2
  • Nirogacestat (γ-Secretase Inhibitor) has shown benefit in progression-free survival and symptom control 2
• Radiotherapy may be considered for unresectable tumors in critical locations 2

Management of Other Extracolonic Manifestations

• Osteomas can be surgically removed if causing functional or aesthetic concerns 6
• Epidermoid cysts can be excised if symptomatic or for cosmetic reasons 4
• Regular screening for other extracolonic manifestations is recommended 1

Surveillance

Pre-Diagnosis Screening

• In families with known Gardner syndrome/FAP:
  • Colorectal screening should begin at 10-12 years of age 1
  • Flexible sigmoidoscopy every 2 years is adequate due to the universal distribution of adenomas 2
  • Screening should continue lifelong in mutation carriers 2

Post-Colectomy Surveillance

• After colectomy, patients require lifelong surveillance for:
  • Rectal polyps if rectum is preserved 1
  • Duodenal and periampullary adenomas 2
  • Desmoid tumors, particularly after abdominal surgery 2

Genetic Counseling

• Each child of an affected parent has a 50% chance of inheriting the predisposition 1
• Between one-third and half of new FAP cases represent de novo mutations with no family history 1
• Genetic testing of family members allows for targeted surveillance of only those carrying the mutation 1
• Young age, male gender, abdominal site, family history of cancer, and absence of CTNNB1 tumor mutation are risk factors for Gardner syndrome in patients with desmoid tumors 2

Pitfalls and Caveats

• Failure to recognize extracolonic manifestations may lead to delayed diagnosis and increased risk of colorectal cancer 5
• Desmoid tumors have a variable and unpredictable course and may be locally aggressive with high symptom burden 2
• The position of the APC mutation may influence surgical decisions and disease severity 1
• Multidisciplinary team approach involving gastroenterologists, surgeons, geneticists, and other specialists is crucial for optimal management 1