Familial adenomatous polyposis (FAP)

Overview

•Autosomal dominant - germline mutation in APC gene (chromosome 5q21)

•NOT the most common inherited colorectal cancer - that is Lynch syndrome (HNPCC) (~3-5%); FAP accounts for <1%

•Near-100% lifetime risk of colorectal cancer if untreated; mean age of cancer ~35-40 years

•Hundreds to thousands of adenomatous polyps developing from teens onward

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FAP vs Lynch syndrome: Lynch syndrome is the most common inherited colorectal cancer. FAP is more dramatic (100% penetrance, thousands of polyps) but far less common.

Presentation

•Rectal bleeding - bright red blood from friable adenomas

•Change in bowel habit - looser stools

•Iron deficiency anaemia - from chronic low-grade bleeding

•Often diagnosed via family screening in teens/early twenties before symptoms develop

Investigations

🥇 First-line

•Colonoscopy - identifies and biopsies adenomatous polyps

•Genetic testing: APC gene mutation analysis - confirms diagnosis; first-degree relatives offered testing from mid-teens

•Upper GI endoscopy (OGD): screens for duodenal/gastric adenomas; Spigelman staging guides surveillance intervals

•FBC and iron studies: assess for iron deficiency anaemia

Management

•Goal: prophylactic colectomy before malignant transformation, typically before age 25-30

🥇 First-line

•Restorative proctocolectomy with ileo-anal pouch anastomosis (IPAA) - removes entire colon and rectum, maintains continence

•Alternative: Total colectomy with ileo-rectal anastomosis (IRA) - if fewer rectal polyps; ongoing rectal surveillance required

•Chemoprevention: celecoxib (COX-2 inhibitor) reduces polyp burden adjunctively; sulindac ± tamoxifen for desmoid tumours in Gardner's - does not replace surgery

•Upper GI surveillance lifelong - duodenum (periampullary region) is second most common site of malignancy in FAP

Complications

•Colorectal cancer - virtually inevitable without surgery

•Duodenal/periampullary cancer - second most common FAP-related malignancy

•Desmoid tumours (Gardner's) - locally aggressive, retroperitoneal; can cause ureteric/bowel obstruction

•Papillary thyroid carcinoma (Gardner's)

Gardner's Syndrome (FAP Variant)

Classic FAP plus extra-colonic features - same APC mutation, same near-100% colorectal cancer risk.

Extra-colonic features of Gardner's syndrome

Osteomas - skull and mandible

Epidermoid cysts - skin

Desmoid tumours - often retroperitoneal

Thyroid carcinoma - papillary type

Supernumerary teeth

CHRPE - congenital hypertrophy of retinal pigment epithelium

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The polyps in Gardner's syndrome carry the same near-100% malignant risk as classic FAP - the statement 'polyps are mainly benign' is FALSE and a classic exam trap.