FAP / APC Polyposis
This one starts in childhood — recognize it and refer early.
Unlike Lynch, classic FAP means colorectal cancer is near-certain without a colectomy, and adenomas
appear in adolescence. The FP wins are recognizing polyposis, testing at-risk children by age 10, and
getting them into a polyposis registry / GI — not managing it in primary care.
Draft reference — pending Dr. Anderson's clinical sign-off. Cite the primary source, not this page.
What it is
Familial adenomatous polyposis results from a germline pathogenic variant in APC, inherited autosomal dominant. It runs as three phenotypes — classic FAP, attenuated FAP, and GAPPS — that differ in polyp burden, cancer risk, and which organ is at stake.
Family history can be absent
About 20–25% of cases are de novo — a quarter of patients have no affected parent. A clean family history does not rule out FAP when the colonoscopy shows adenomatous polyposis.
The three phenotypes
Classic FAP
- Polyp burden:
- Hundreds to thousands of colorectal adenomas
- Cancer risk:
- Near-certain without colectomy (historical untreated natural history); mean colorectal cancer diagnosis ~39 years. Colectomy is preventive, not optional.
- Onset:
- Adenomas by adolescence (mean ~16, range 7–36); 95% have polyps by age 35
- Colon management:
- Colonoscopy (or flexible sigmoidoscopy) every 1–2 years starting age 10–15; colectomy once the polyp burden is unmanageable (multiple adenomas >10 mm, high-grade dysplasia, or symptoms).
- Note:
- The prototype — near-inevitable colorectal cancer without surgery. A childhood-onset, surgical-referral syndrome, not an adult screening problem.
- What to tell the patient:
- Frame it plainly: the question is not whether to remove the colon but when. Get the child into a polyposis registry / GI early. Colectomy prevents the colorectal cancer; residual risk then shifts to the duodenum and any rectal remnant.
GeneReviews: APC-Associated Polyposis Conditions (2022).
Attenuated FAP (AFAP)
- Polyp burden:
- Fewer polyps — typically 10–100 (average ~30), right-sided predominance
- Cancer risk:
- ~70% lifetime by age 80
- Onset:
- Later — cancer typically ages 50–55 (10–15 years later than classic)
- Colon management:
- Colonoscopy (NOT sigmoidoscopy — polyps are proximal/right-sided) starting in late adolescence; low burden may be managed by periodic polypectomy rather than immediate colectomy.
- Note:
- The mimic of Lynch and MUTYH-associated polyposis — fewer polyps, later onset. Colonoscopy (not sigmoidoscopy) matters because the polyps sit in the right colon.
- What to tell the patient:
- Explain it's a milder, later form but still high-risk — surveillance is lifelong and the scope must reach the right colon. Some patients avoid colectomy with diligent polypectomy.
GeneReviews: APC-Associated Polyposis Conditions (2022).
GAPPS
- Polyp burden:
- Proximal gastric fundic-gland polyposis; minimal duodenal / colonic involvement
- Cancer risk:
- Low colorectal involvement — the risk here is GASTRIC adenocarcinoma, ~13–25% lifetime
- Onset:
- Variable; gastric-predominant
- Colon management:
- Gastric-focused: upper-endoscopy surveillance, and risk-reducing gastrectomy is considered. The colon is largely spared.
- Note:
- Gastric Adenocarcinoma and Proximal Polyposis of the Stomach — caused by APC promoter 1B variants. The odd one out: a gastric, not colorectal, polyposis. Recognize it so gastric cancer risk isn't missed.
- What to tell the patient:
- Point out this variant spares the colon but drives gastric cancer risk — surveillance and the risk-reducing surgery conversation are about the stomach, not the colon.
GeneReviews: APC-Associated Polyposis Conditions (2022).
It isn't only the colon
After colectomy, the leading causes of cancer death are extracolonic. These are what the FP should keep on the radar:
- Duodenal & ampullary adenomas → cancer — the top cancer-death cause after the colon is removed. Upper endoscopy (EGD) from age 20–25, interval set by Spigelman stage (Stage 0–I: every 5 yr; II: 3 yr; III–IV: annual).
- Desmoid tumors — locally aggressive fibromatosis, often intra-abdominal, frequently triggered by surgery; a major cause of morbidity/mortality. Annual abdominal palpation; image only if symptomatic. Higher risk with 3' APC variants and a family history of desmoids.
- Hepatoblastoma — in infants/young children: screen with AFP + abdominal ultrasound (± palpation) every 3–6 months until age 5.
- Papillary thyroid cancer (cribriform-morular variant, young women) — thyroid ultrasound every 2–5 years from late adolescence.
- Gardner / Turcot features — osteomas, epidermoid cysts, supernumerary teeth, and CHRPE (congenital hypertrophy of the retinal pigment epithelium, a benign exam clue); CNS tumors (medulloblastoma) in the Turcot phenotype.
Surveillance timeline
| Target | Start | What / interval |
|---|---|---|
| Genetic testing (at-risk child) | by age 10 (classic); late adolescence for AFAP | Predictive testing to plan colonoscopy |
| Colon (classic FAP) | age 10–15 | Colonoscopy/sigmoidoscopy every 1–2 yr → colectomy |
| Colon (AFAP) | late adolescence | Colonoscopy (right-sided) every 1–2 yr |
| Duodenum / ampulla | age 20–25 | EGD; interval by Spigelman stage |
| Thyroid | late adolescence | Ultrasound every 2–5 yr |
| Hepatoblastoma (infant) | birth → age 5 | AFP + ultrasound every 3–6 mo |
The polyposis differential
When you see adenomatous polyposis, sort it out — the management diverges:
- Classic FAP — hundreds+ polyps, childhood onset, autosomal dominant.
- Attenuated FAP — typically 10–100 polyps (average ~30), later onset; overlaps the two below.
- MUTYH-associated polyposis — recessive (both parents carriers, no vertical transmission), also ~10–100 polyps. Test APC and MUTYH together when polyps are in the attenuated range. (GeneReviews: MUTYH Polyposis)
- Lynch syndrome — few or no polyps, MMR-deficient / MSI-high tumor. A different mechanism entirely.
The family-physician move
- Suspect it — adenomatous polyposis on a scope, colorectal cancer in a young adult, or a child of an affected parent. Remember a quarter are de novo.
- Refer to genetics and a polyposis registry / GI; testing an at-risk child by age 10 drives the colonoscopy plan.
- Don't stop at the colon — ensure duodenal (EGD/Spigelman), thyroid, and infant hepatoblastoma surveillance are in place.
- Send affected relatives for cascade testing — see Inheritance & Family History.
Source: GeneReviews: APC-Associated Polyposis Conditions (2022); surveillance per NCCN. Autosomal dominant (~20–25% de novo); first-degree relatives of a carrier have a 50% chance of inheriting a known familial variant. General education for clinicians, not a substitute for formal genetic counseling.