Table 1.

Clinical Features and Genes Associated with Hereditary Colorectal Cancer Syndromes

Syndrome	Clinical Features	Gene (s)	Management*	Evidence for Recommendation
Lynch Syndrome	MMR deficiency phenotype in tumors (MSI) Accelerated adenoma-carcinoma sequence CRC risk= 30–70% over lifetime Risk for extracolonic cancers	MLH1 MSH2 MSH6 PMS2 Tacstd1/EpCAM Mutations detected in 70%	Colonoscopy q 1–2 years starting at age 20–25y Consider Upper endoscopy 3–5 years, starting at age 30–35y Consider endometrial cancer screening vs prophylactic hysterectomy	Cohort Studies10, 12 Expert Opinion14
Familial Adenomatous Polyposis (FAP)
Classic Attenuated	100s–1000s colorectal adenomas Risk for duodenal and ampullary adenoca Risk for desmoid tumors, thyroid CA CRC risk 90% without surgery 10–99 colorectal adenomas CRC risk is variable	APC mutations detected in 90% MutYH (biallelic) APC, MutYH mutations detected in ~10%	Colonoscopy q 1–2 years, starting at age 10–12y, colectomy for large polyp burden Upper endoscopy q 1–3 years Consider thyroid ultrasound Colonoscopy q 1–2 years, beginning at age 20–25y Upper endoscopy q 1–3 years	Expert Opinion Expert Opinion13 Expert Opinion13
Peutz Jeghers syndrome	2 ≥Hamartomatous polyps in small bowel Mucocutaneous pigmentation (mouth/ lips, fingers) Cumulative cancer risks 80–90% (colorectal, breast, gastric, pancreatic)	STK11 mutations detected in 50–70%	Upper endoscopy every 2–3 years starting in late teens Small bowel visualization (eg. capsule endoscopy, CT/MR enterography, small bowel follow through) every 1–3y starting at age 8–10y Colonoscopy every 2–3 years, starting in late teens Pancreas screening (MRCP or EUS) every 1–2 y, starting at age 25–30y. Mammogram and Breast MRI, yearly, starting at age 25y. Testicular exam/ultrasound yearly, starting at age 10y Transvaginal Ultrasound, yearly, starting at age 18y	Expert Opinion13,27
Juvenile Polyposis Syndrome	>3–5 juvenile polyps in GI tract Some associated with congenital heart disease, Hereditary hemorrhagic telangiectasia	SMAD4 BMPR1A ENG Mutations detected in <50%	Upper endoscopy q 1–3 years starting age 15y Colonoscopy q 1–3y starting age 15y	Expert Opinion13
Cowden Syndrome	Macrocephaly Increased risk for cancer (breast, thyroid, endometrial) Variable colorectal polyp phenotype (adenoma, hamartoma, sessile serrated, ganglioneuroma) CRC risk can be variable	PTEN Mutations detected in 65–80%	Colonoscopy q 3–5 years, beginning age 30–35y Mammogram and Breast MRI, yearly, starting at age 30–35y. Annual thyroid ultrasound starting by age 18y	Expert Opinion13,30

CRC= colorectal cancer

MMR= Mismatch repair

MSI= Microsatellite Instability

^*Reference: *NCCN Clinical Practice Guidelines in Oncology Version 1.2013, nccn.org