Management and Treatment of Gardner Syndrome (Familial Adenomatous Polyposis)

Gardner syndrome requires prophylactic colectomy as the only effective treatment to prevent the inevitable development of colorectal cancer. 1

Overview and Diagnosis

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
The syndrome is caused by germline mutations in the APC gene with an autosomal dominant inheritance pattern 1, 2
Diagnostic approach includes genetic testing for APC mutations, which are detected in approximately 80% of patients with numerous adenomas 2
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, 2

For at-risk individuals with a known family mutation, genetic testing should replace endoscopic screening 2
Only mutation-positive individuals require endoscopic surveillance to evaluate adenoma development and determine timing for prophylactic surgery 2
In classic FAP, colorectal screening should begin at 10-12 years of age due to the high risk of early-onset colorectal cancer 1

Prophylactic colectomy is the only effective treatment to prevent colorectal cancer development, which occurs in virtually 100% of untreated patients 3, 4
The preferred surgical procedure is restorative proctocolectomy with ileal pouch anal anastomosis (RPC/IPAA) with mucosectomy, as it aims to eliminate all colorectal mucosa without requiring a permanent ostomy 4, 5
The position of the APC mutation may influence surgical decisions, as it correlates with the severity of rectal polyposis 2
Surgery is typically performed when the patient is in their early teens or when significant polyp burden develops 3

Regular upper endoscopic surveillance is essential due to the high frequency of duodenal involvement 3
Periampullary carcinoma is a significant cause of morbidity and mortality after colectomy 4

Intra-abdominal desmoid tumors are a significant cause of morbidity and mortality in FAP patients after colectomy 4
Desmoid tumors occur in 7.5% to 16% of FAP patients, with risk factors including positive family history, previous abdominal surgery, and specific APC mutation sites 1
Management may include surgical excision, but there is no definitive treatment available for all cases 4

Epidermoid cysts and other skin manifestations can be treated through surgical excision 3, 5
Treatment approach depends on location, size, and number of lesions 5

Genetic counseling is essential for patients and families 5
Each child of an affected parent has a 50% chance of inheriting the predisposition 2
Between one-third and half of new FAP cases represent de novo mutations with no family history 2
Genetic testing of family members allows for targeted surveillance of only those carrying the mutation 2, 6

The position of the APC mutation correlates with disease severity and extracolonic manifestations 2
Early diagnosis through genetic testing and appropriate management significantly reduces the risk of colorectal cancer development 7
Multidisciplinary team approach involving gastroenterologists, surgeons, geneticists, and other specialists is crucial for optimal management 1