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Difficulty: HardGastroenterology and Hepatology

Match each clinical presentation of a hereditary gastrointestinal polyposis or cancer syndrome with its corresponding underlying genetic mutation.

  • A 32-year-old man with childhood intussusception, buccal mucocutaneous hyperpigmentation, and multiple hamartomatous intestinal polyps.Mutation in the STK11 (LKB1) gene
  • A 45-year-old woman with early-onset right-sided colon cancer, a family history of endometrial cancer, and 3 adenomatous colonic polyps.Mutation in DNA mismatch repair (MMR) genes
  • A 25-year-old woman with macrocephaly, facial trichilemmomas, a history of breast cancer, and widespread hamartomatous gastrointestinal polyps.Mutation in the PTEN gene
  • A 38-year-old man with >100 adenomatous colon polyps, mandibular osteomas, and congenital hypertrophy of the retinal pigment epithelium.Mutation in the APC gene
  • A 30-year-old man with >100 adenomatous colon polyps and an autosomal recessive pattern of inheritance (unaffected parents, affected sibling).Biallelic mutations in the MUTYH gene

Answer

The correct matches pair Peutz-Jeghers syndrome with STK11, Lynch syndrome with MMR genes, Cowden syndrome with PTEN, FAP/Gardner syndrome with APC, and MUTYH-associated polyposis with MUTYH.
Gastrointestinal polyposis and hereditary cancer syndromes each have distinct phenotypic manifestations tied to specific genetic mutations. Peutz-Jeghers syndrome presents with hamartomas and mucocutaneous hyperpigmentation (STK11). Lynch syndrome presents with right-sided colon cancer and endometrial cancer, with few or no polyps, due to defective DNA mismatch repair. Cowden syndrome presents with hamartomas, macrocephaly, and trichilemmomas (PTEN). Familial adenomatous polyposis (and its Gardner variant) presents with >100 adenomatous polyps, osteomas, and CHRPE due to APC gene mutations. MUTYH-associated polyposis clinically resembles FAP but follows an autosomal recessive inheritance pattern.

Step-by-Step Solution

1
Analyze the clinical presentation of the patient with buccal hyperpigmentation and hamartomas.
Identified as Peutz-Jeghers syndrome.
Mucocutaneous hyperpigmentation and hamartomatous polyps are the classic diagnostic criteria for Peutz-Jeghers.
2
Analyze the patient with right-sided CRC, endometrial cancer, and few polyps.
Identified as Lynch syndrome (HNPCC).
Early-onset right-sided colon cancer and a strong family history of endometrial cancer without diffuse polyposis are characteristic of Lynch syndrome.
3
Analyze the presentation of the patient with macrocephaly, trichilemmomas, and breast cancer.
Identified as Cowden syndrome.
The triad of macrocephaly, characteristic mucocutaneous lesions (trichilemmomas), and hamartomatous polyps points definitively to Cowden syndrome.
4
Analyze the patient with >100 adenomas, osteomas, and CHRPE.
Identified as Gardner syndrome, a variant of Familial Adenomatous Polyposis (FAP).
Profuse adenomatous polyposis combined with extraintestinal manifestations like osteomas is pathognomonic for FAP.
5
Analyze the patient with >100 adenomas and an autosomal recessive family history.
Identified as MUTYH-associated polyposis (MAP).
MAP clinically mimics FAP but is distinguished by its autosomal recessive inheritance and MUTYH gene involvement.
6
Correlate each identified syndrome with its underlying genetic mutation.
Matched Peutz-Jeghers with STK11, Lynch with MMR, Cowden with PTEN, FAP with APC, and MAP with MUTYH.
These are the established genetic etiologies for each respective hereditary syndrome.

Key Concept

Clinical and genetic correlation of hereditary gastrointestinal polyposis and cancer syndromes.
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Topics

Gastroenterology and Hepatology

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