ASGE Annual GI Advanced Practice Provider Course (Virtual) (Day One) | March 2026-Hereditary Polyposis Syndromes

Pdf Summary

The document reviews major hereditary colorectal polyposis and cancer syndromes and highlights when gastroenterologists should refer patients for genetic evaluation. Referral is recommended for colorectal cancer (CRC) diagnosed before age 50, patients with multiple primary cancers, suspicious personal/family histories for Lynch syndrome, tumors with mismatch repair deficiency, individuals with >10–20 cumulative adenomas, those with multiple hamartomas, or families with a known hereditary colorectal cancer syndrome. A polling example implies the most appropriate genetics referral is a patient with numerous adenomas (e.g., ~10 adenomas at age 45).

Key syndromes summarized include:

- <strong>Familial Adenomatous Polyposis (FAP)</strong>: Autosomal dominant APC mutation; classic FAP causes hundreds to thousands of adenomas with near-100% CRC risk, often prompting colectomy near diagnosis. Attenuated FAP presents with fewer polyps (often 10–100/10–20) but still high CRC risk; some patients may be managed with intensive polypectomy and annual surveillance. FAP also increases risk for duodenal/ampullary and gastric cancers, desmoid tumors, thyroid cancer, medulloblastoma, and retinal pigment changes. At-risk relatives should undergo genetic testing and early/regular endoscopic surveillance.

- <strong>MUTYH-Associated Polyposis (MAP)</strong>: The main autosomal recessive polyposis syndrome due to biallelic MUTYH variants, often presenting around age ~45 with frequently right-sided disease. Suggested surveillance includes colonoscopy every 1–2 years from age 25–30 and upper endoscopy/duodenoscopy starting age 30–35.

- <strong>Lynch syndrome (HNPCC)</strong>: Autosomal dominant mismatch repair gene defects (MLH1, MSH2, MSH6, PMS2, EPCAM) with earlier, often right-sided CRC and elevated risks of endometrial, ovarian, gastric, small bowel, and urothelial cancers; clinical criteria (Amsterdam-type) are listed.

- <strong>Hamartomatous syndromes</strong>: <strong>Peutz-Jeghers (STK11)</strong> with mucocutaneous pigmentation and small-bowel hamartomas plus broad cancer risks; <strong>Juvenile Polyposis (SMAD4/BMPR1A/ENG)</strong> with CRC and gastric cancer risk and association with HHT; and <strong>PTEN hamartoma tumor syndromes</strong> (e.g., Cowden) with multi-organ hamartomas and cancer predisposition.

The talk concludes by stressing careful family history, review of prior colonoscopy/pathology reports, and attention to high polyp burden (adenomas or proximal sessile serrated lesions) as triggers for genetics referral.

Asset Subtitle

Vijaya Rao, MD, FASGE

Keywords

hereditary colorectal cancer syndromes

genetic referral criteria

familial adenomatous polyposis (FAP)

APC mutation

attenuated FAP

MUTYH-associated polyposis (MAP)

Lynch syndrome (HNPCC)

mismatch repair deficiency (MMR)

hamartomatous polyposis syndromes

multiple colorectal adenomas (>10–20)