Familial Adenomatous polyposis (FAP) ✅

Related Subjects: |Zollinger Ellison syndrome |Gastrinoma |VIPomas |Carcinoid Tumour Syndrome |Familial Adenomatous polyposis (FAP) |Colorectal cancer |Colorectal polyps |Ulcerative Colitis |Acute Severe Colitis |Crohn's disease |Coeliac disease |Dermatitis Herpetiformis

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

ℹ️ About

• 📊 Accounts for 0.5–1% of all colorectal cancers; prevalence ≈ 1 in 10,000.
• 🧬 Classic FAP is autosomal dominant.
• ⏳ Average age of colorectal cancer onset in classic FAP: 39 years.
• ⚠️ Attenuated FAP (AFAP) presents later (~55 years) with fewer polyps.

Genetics 🧬

• APC gene mutation (chromosome 5q21-22) – one defective copy → classic FAP.
• MUTYH-associated polyposis (MAP) – autosomal recessive variant.
• 🎗️ Nearly all untreated patients will develop colorectal carcinoma if not monitored or treated.

Aetiology & Pathophysiology 🧬

• 📍 APC = tumour suppressor “gatekeeper”; mutation → uncontrolled epithelial proliferation.
• 👁️ Retinal pigment epithelial hypertrophy may be detectable in childhood.
• 🌱 AFAP → fewer polyps, later onset, sometimes right-sided colon predilection.
• 🪢 Extra-colonic manifestations include desmoid tumours, osteomas, epidermoid cysts, and gastric polyps.

🩺 Clinical Features

• 🔎 >100 colorectal adenomatous polyps typical of classic FAP.
• 👩‍⚕️ Polyps appear in adolescence; colorectal cancer almost inevitable by age 40 if untreated.
• 🦷 Extra-colonic signs: jaw osteomas, dental cysts, retinal pigmentation, epidermoid cysts, desmoid tumours, gastric polyps.

🔎 Investigations

• 📹 Colonoscopy surveillance: Detects hundreds–thousands of polyps; interval as per NICE/BSG guidance (annually once polyps develop).
• 🧬 Genetic testing: Confirms APC or MUTYH mutations; allows at-risk relatives to undergo predictive testing.
• 🔬 Consider upper GI endoscopy for duodenal/gastric polyps (Spigelman scoring for duodenal polyposis).

💊 Management

• 🕵️ Early and regular colonoscopic surveillance starting in adolescence (age 10–12 for classic FAP).
• ✂️ Elective surgery when polyp burden becomes unmanageable or high-risk features appear:
• Panproctocolectomy with end ileostomy
• Colectomy with ileorectal anastomosis (rectum must continue to be surveilled)
• Proctocolectomy with ileal pouch–anal anastomosis (currently preferred in many centres)
• 👨‍👩‍👧 Family members: genetic counselling, predictive testing, and surveillance for mutation carriers.
• 🧑‍⚕️ Multidisciplinary care: gastroenterology, colorectal surgery, genetics, dietetics, and psychosocial support.
• 🔬 Extra-colonic disease: monitor desmoid tumours, duodenal polyps, gastric polyps, thyroid disease, and hepatoblastoma (in children).

Cases - Familial Adenomatous Polyposis

• Case 1 (Classic FAP – teenager) 👦 16-year-old with rectal bleeding; colonoscopy: hundreds of polyps. APC mutation confirmed. Management: Surveillance and elective proctocolectomy with ileal pouch–anal anastomosis. Outcome: Recovery good; long-term follow-up for extracolonic manifestations.
• Case 2 (Attenuated FAP – adult) 👩‍🦳 52-year-old with iron-deficiency anaemia; 25 right-colon polyps; APC variant confirmed. Management: Colectomy with ileorectal anastomosis; ongoing rectal surveillance. Outcome: No malignancy; regular endoscopic follow-up maintained.
• Case 3 (MAP variant) 👨 38-year-old with no family history; >100 polyps; biallelic MUTYH mutation. Management: Panproctocolectomy; siblings offered carrier testing. Outcome: Recovery uneventful; ongoing duodenal polyp and desmoid monitoring.

Teaching Commentary 🧑‍⚕️

FAP exemplifies a hereditary cancer syndrome. Without intervention, colorectal cancer is nearly universal by middle age. 🌟 Key learning points:

• APC mutation = autosomal dominant; MUTYH mutation = autosomal recessive.
• Start colonoscopic surveillance in adolescence; repeat intervals as per polyp burden and NICE/BSG guidance.
• Surgery is preventive; type depends on polyp burden, rectal involvement, and quality-of-life considerations.
• Extra-colonic disease (desmoid tumours, osteomas, gastric polyps) requires regular monitoring.
• Family screening is critical for early detection and prevention.

References 📚

• NICE CG184 – Colorectal cancer: diagnosis and management
• BSG Guidelines – Familial Adenomatous Polyposis
• NICE CKS – Colorectal cancer (genetics)