What is the management and treatment of Gardner syndrome?

Management and Treatment of Gardner Syndrome

The management of Gardner syndrome requires a multidisciplinary approach with prophylactic colectomy as the only effective treatment to prevent colorectal cancer, which has 100% risk in these patients. 1

Diagnosis and Evaluation

• Gardner syndrome is a variant of Familial Adenomatous Polyposis (FAP) with extracolonic manifestations including:

  • Colorectal polyps (hundreds to thousands)
  • Osteomas
  • Skin cysts (epidermoid)
  • Desmoid tumors (aggressive fibromatosis)
  • Congenital hypertrophy of retinal pigmented epithelium
  • Other manifestations: thyroid tumors, brain tumors, supernumerary teeth 2

• Genetic testing:

  • Germline mutations in the APC gene on chromosome 5q21 2
  • Gene testing should start with an affected individual
  • If causative mutation is detected, presymptomatic testing can be offered to at-risk family members 2

Colorectal Management

1. Screening:

   • In families with classic FAP, flexible sigmoidoscopy every 2 years starting at age 12-14 years 2
   • When causative mutation is not identified, all at-risk family members should undergo colorectal screening 2

2. Surgical Management:

   • Prophylactic colectomy is the only effective treatment to prevent progression to colorectal cancer 1, 3
   • Preferred procedure: Restorative proctocolectomy with ileal pouch anal anastomosis (RPC/IPAA) with mucosectomy 3
   • Surgery should be considered when adenomas are detected
   • Extended colectomy should be discussed at diagnosis due to 16% risk of developing second CRC after 10 years 2

Management of Extracolonic Manifestations

Desmoid Tumors

• Occur in 7.5-16% of FAP patients 2
• Risk factors: positive family history, abdominal surgery, specific APC mutation sites 2
• Management approach:
  1. Initial active surveillance with regular MRI scans and clinical review 2
  2. For progressing cases, medical therapy is standard treatment 2
  3. Exception: desmoid tumors in abdominal wall where surgery has low relapse rates 2
  4. Systemic options for unresectable/progressive tumors:
     • Sorafenib (confirmed activity in placebo-controlled study) 2
     • Pegylated liposomal doxorubicin
     • Pazopanib
     • Low-dose chemotherapy including oral vinorelbine 2
     • Nirogacestat (γ-Secretase Inhibitor) shown to improve progression-free survival and symptom control 2
  5. Radiotherapy may be considered for unresectable tumors in critical locations 2
  6. Alternative approaches: percutaneous radiofrequency ablation for unresectable intra-abdominal desmoids 4

Duodenal Polyps

• Regular upper endoscopic surveillance is essential due to high frequency of duodenal involvement 1

Skin Manifestations

• Surgical excision of epidermoid cysts as needed 1

Osteomas

• Surgical removal if symptomatic or for cosmetic reasons

Long-term Follow-up

• Lifelong surveillance is required for:

  1. Colorectal remnants (if present)
  2. Duodenal polyps (high risk of periampullary carcinoma)
  3. Thyroid abnormalities
  4. Development of new desmoid tumors
  5. Retinal examination 1

• Follow-up schedule:

  • Physical exam with abdominal/pelvic CT every 3-6 months for 2-3 years
  • Then every 6 months for next 2 years
  • Then annually 2
  • Consider chest imaging 2

Special Considerations

• Genetic counseling is essential for all patients and family members
• Fertility preservation discussions should occur before surgery in young patients
• Pain management, physiotherapy, and psychological support should be considered for patients with desmoid tumors 2

Gardner syndrome management requires a coordinated approach between colorectal surgeons, gastroenterologists, geneticists, and oncologists to address both the colonic and extracolonic manifestations of this complex syndrome.