Makindo Medical Notes

👁️ Patients with Familial Adenomatous Polyposis (FAP) often have congenital hypertrophy of the retinal pigmented epithelium — an important extra-intestinal clue.

About

• 📊 Accounts for 0.5–1% of all colorectal cancers; prevalence ≈ 1 in 10,000.
• 🧬 Inherited as an autosomal dominant condition (classic FAP).
• ⏳ Average age of colorectal cancer onset in classic FAP: 39 years.
• ⚠️ In attenuated FAP (AFAP), onset is later (~55 years).

Genetics

• 🧬 Usually due to APC gene mutation (chromosome 5q21-22). One defective copy → disease.
• 🔄 MUTYH-associated polyposis (MAP) is a variant, inherited autosomal recessively.
• 🎗️ Nearly all patients with untreated FAP will develop colorectal carcinoma.

Aetiology & Pathophysiology

• 📍 APC gene functions as a tumour suppressor “gatekeeper.” Mutation = uncontrolled cell growth.
• 👁️ Retinal pigment epithelial hypertrophy may be detectable in childhood.
• 🌱 Attenuated FAP → fewer, later-onset polyps.
• 🪢 Desmoid tumours are common extra-colonic manifestations, often recurrent after surgery.

Clinical Features

• 🔎 Diagnosis usually requires >100 colorectal adenomatous polyps.
• 👩‍⚕️ Polyps start in adolescence; cancer almost inevitable by age 40 if untreated.
• 🦷 Extra-colonic features: dental cysts, jaw osteomas, retinal pigmentation.
• 🩺 Other associations: epidermoid cysts, gastric hamartomas, desmoid tumours.

Investigations

• 📹 Surveillance colonoscopy: hundreds–thousands of polyps, increasing with age.
• 🧬 Genetic testing: confirms APC or MUTYH mutations; enables family screening.

Management

• 🕵️ Surveillance colonoscopy starting in teenage years.
• 🩺 Elective surgery when polyp burden becomes unmanageable:
  • ✂️ Panproctocolectomy with end ileostomy.
  • ✂️ Colectomy + ileorectal anastomosis (rectum must still be monitored).
  • ✂️ Proctocolectomy + ileal pouch–anal anastomosis (preferred today).
• 👨‍👩‍👧 Family members require genetic counselling and screening.

Cases — Familial Adenomatous Polyposis

• Case 1 (Classic FAP in teenager): 👦 A 16-year-old boy undergoes colonoscopy for rectal bleeding; hundreds of polyps are seen throughout the colon. Genetic testing confirms APC mutation. Management: Surveillance → elective proctocolectomy with ileal pouch–anal anastomosis. Outcome: Good recovery; enrolled in long-term surveillance for extracolonic disease.
• Case 2 (Attenuated FAP): 👩‍🦳 A 52-year-old woman presents with iron-deficiency anaemia. Colonoscopy shows 25 adenomas in the right colon. Genetic analysis: attenuated APC mutation. Management: Colectomy with ileorectal anastomosis; rectal surveillance continued. Outcome: No cancer at diagnosis; remains under close endoscopic review.
• Case 3 (MAP variant): 👨 A 38-year-old man with no family history presents with abdominal pain. Colonoscopy: >100 polyps. Genetic testing: biallelic MUTYH mutations. Management: Panproctocolectomy performed; siblings offered carrier testing. Outcome: Post-surgical recovery uneventful; ongoing monitoring for duodenal polyps and desmoid tumours.

Teaching Commentary 🧑‍⚕️

FAP is a classic example of a cancer predisposition syndrome. Without intervention, colorectal cancer is almost universal by middle age. 🌟 Key learning points: • APC mutation = autosomal dominant, while MUTYH mutation = recessive. • Surveillance colonoscopy starts in adolescence. • Surgery is preventive but must be balanced against quality of life. • Extra-colonic disease (desmoids, gastric polyps, osteomas) requires vigilance. Early recognition and family screening are lifesaving.