What genetic testing options are available for patients suspected of having Familial Adenomatous Polyposis?

For patients suspected of having Familial Adenomatous Polyposis (FAP), genetic testing primarily involves analysis of the APC gene to identify pathogenic variants responsible for the condition. Testing typically starts with mutation screening of the APC gene in an affected individual, if available, to confirm the diagnosis and guide predictive testing in relatives. If no mutation is found in APC but clinical suspicion remains high, testing for mutations in the MUTYH gene may be considered, as biallelic MUTYH mutations cause a recessive form of polyposis. Genetic testing should be accompanied by pre-test genetic counselling to discuss the implications, benefits, and limitations of testing, including the possibility of variants of uncertain significance or negative results. Testing is ideally performed in specialist genetics clinics or services with expertise in hereditary colorectal cancer syndromes. The use of gene panel testing that includes APC, MUTYH, and other relevant genes associated with polyposis syndromes is increasingly common to provide a comprehensive assessment. This approach aligns with current UK clinical genetics practice and is supported by recent literature emphasizing the importance of mutation detection for diagnosis, risk assessment, and management planning in FAP Petersen 1996Lal & Gallinger 2000Kyriakidis et al. 2023 NICE NG241.

Key points:

• Genetic testing focuses on APC gene mutation analysis as the primary diagnostic tool for FAP.
• Testing of MUTYH gene is considered if APC mutations are not found but clinical suspicion persists.
• Pre-test genetic counselling is essential to inform patients about the testing process and implications.
• Testing is best performed in specialist genetics services with access to gene panel testing.
• Gene panel testing may include APC, MUTYH, and other polyposis-related genes for comprehensive evaluation.