A 28-year-old woman from rural India presents with multiple colonic polyps detected on colonoscopy. Genetic testing reveals a germline APC mutation. Which feature best distinguishes familial adenomatous polyposis (APC mutation) from Lynch syndrome (mismatch repair gene mutation)?

Question

Accepted Answer

B. Presence of extracolonic manifestations (osteomas, desmoid tumors, congenital hypertrophy of retinal pigment epithelium). ## Distinguishing FAP from Lynch Syndrome

### Key Discriminating Feature

**Key Point:** Familial adenomatous polyposis (APC mutation) is characterized by **pathognomonic extracolonic manifestations** (osteomas, desmoid tumors, congenital hypertrophy of retinal pigment epithelium [CHRPE], jaw cysts), whereas Lynch syndrome (mismatch repair defects) has **minimal extracolonic features** and primarily affects the colon and other internal organs (stomach, ovary, ureter).

### Comparative Table

| Feature | FAP (APC) | Lynch Syndrome (MMR) |
|---------|-----------|---------------------|
| **Polyp count** | Hundreds to thousands | 10–100 adenomas |
| **Polyp type** | Adenomatous (uniform) | Adenomatous (scattered) |
| **CRC risk** | ~100% by age 50 | ~70–80% by age 70 |
| **Osteomas** | Yes (jaw, skull) | No |
| **Desmoid tumors** | Yes (10–15%) | No |
| **CHRPE** | Yes (75%) | No |
| **Jaw cysts** | Yes (common) | No |
| **Extracolonic cancers** | Stomach, duodenum, pancreas, thyroid, brain (Turcot variant) | Stomach, ovary, ureter, biliary tract, brain |
| **Inheritance** | Autosomal dominant | Autosomal dominant |
| **Age of CRC onset** | 40–50 years | 45–65 years |

### Why This Matters

**High-Yield:** APC mutations cause a **polyposis phenotype** (hundreds of polyps) with **skeletal and soft tissue manifestations** that are absent in Lynch syndrome. These extracolonic features are the **clinical hallmark** of FAP.

**Clinical Pearl:** A patient with multiple colonic polyps + jaw osteomas + CHRPE on ophthalmology exam → **FAP**. A patient with scattered adenomas + family history of endometrial cancer and ovarian cancer → **Lynch syndrome**.

### Mnemonic

**FAP = "Familial Adenomatous Polyposis" (polyps + bones + desmoids)** vs. **Lynch = "Lynched by internal cancers" (no extracolonic skeletal features)**

[cite:Robbins 10e Ch 7]

Answer

A. Early age of colorectal cancer onset (<50 years)

Answer

C. Increased risk of colorectal cancer approaching 100% by age 50

Answer

D. Autosomal dominant inheritance pattern

A 28-year-old woman from rural India presents with multiple colonic polyps detected on colonoscopy. Genetic testing reveals a germline APC mutation. Which feature best distinguishes familial adenomatous polyposis (APC mutation) from Lynch syndrome (mismatch repair gene mutation)?

Explanation

Distinguishing FAP from Lynch Syndrome

Key Discriminating Feature

Comparative Table

Why This Matters

Mnemonic

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Feature	FAP (APC)	Lynch Syndrome (MMR)
Polyp count	Hundreds to thousands	10–100 adenomas
Polyp type	Adenomatous (uniform)	Adenomatous (scattered)
CRC risk	~100% by age 50	~70–80% by age 70
Osteomas	Yes (jaw, skull)	No
Desmoid tumors	Yes (10–15%)	No
CHRPE	Yes (75%)	No
Jaw cysts	Yes (common)	No
Extracolonic cancers	Stomach, duodenum, pancreas, thyroid, brain (Turcot variant)	Stomach, ovary, ureter, biliary tract, brain
Inheritance	Autosomal dominant	Autosomal dominant
Age of CRC onset	40–50 years	45–65 years