What inherited syndromes cause gastric polyps?

Inherited Syndromes Causing Gastric Polyps

The primary inherited syndromes that cause gastric polyps are Familial Adenomatous Polyposis (FAP), Attenuated FAP, Peutz-Jeghers Syndrome, Juvenile Polyposis Syndrome, and PTEN Hamartoma Tumor Syndrome. 1

Adenomatous Polyposis Syndromes with Gastric Involvement

Familial Adenomatous Polyposis (FAP)

• Causes gastric adenomatous polyps (AP) and cystic fundic gland polyps in patients with hundreds to thousands of colorectal polyps 1
• Due to germline mutations in the APC gene (autosomal dominant inheritance) 1
• Gastric polyps occur alongside duodenal adenomatous polyps 1
• Associated extracolonic features include CHRPE (congenital hypertrophy of retinal pigment epithelium), osteomas, dental anomalies, fibromas, epidermoid cysts, and desmoid tumors 1

Attenuated Familial Adenomatous Polyposis (AFAP)

• Presents with gastric AP and cystic fundic gland polyps similar to classic FAP but with fewer colorectal polyps (10-100) 1
• Also caused by APC gene mutations but with different mutation locations leading to milder phenotype 1
• Same gastric polyp types as classic FAP 1

MUTYH-Associated Polyposis (MAP)

• Produces gastric AP and cystic fundic gland polyps 1
• Caused by biallelic mutations in MUTYH gene (autosomal recessive inheritance) 1
• Typically presents with few to hundreds of colorectal polyps 1

Hamartomatous Polyposis Syndromes with Gastric Involvement

Peutz-Jeghers Syndrome (PJS)

• Causes hamartomatous polyps in the stomach and throughout the GI tract 1
• Due to germline mutations in STK11 gene (autosomal dominant) 1
• Gastric polyps occur alongside small intestine involvement 1
• Distinctive mucocutaneous hyperpigmentation on buccal mucosa, palms, soles of feet, and periorbital regions 1
• Carries increased risk of gastric cancer along with multiple other malignancies 1

Juvenile Polyposis Syndrome (JPS)

• Produces juvenile hamartomatous polyps in the stomach in addition to colorectal involvement 1
• Caused by mutations in BMPR1A or SMAD4 genes (autosomal dominant) 1
• Presents with few to hundreds of polyps 1
• 21% risk of gastric cancer in those with gastric polyps 1
• If SMAD4 mutation present, may have hereditary hemorrhagic telangiectasia (HHT) overlap with risk of CNS, lung, and GI tract arteriovenous malformations 1

PTEN Hamartoma Tumor Syndrome (PHTS)

• Includes gastric juvenile polyposis-type polyps along with hyperplastic and adenomatous polyps 1
• Due to PTEN gene mutations (autosomal dominant); rarely BMPR1A mutations 1
• Associated with trichilemmomas, ganglioneuromas, macrocephaly, autism spectrum disorders, and mucocutaneous hamartomas 1
• Gastric and colorectal involvement documented 1

Additional Syndromes with Gastric Polyp Potential

Hereditary Mixed Polyposis Syndrome (HMPS)

• May involve gastric polyps though specific gastric involvement is less well-characterized 1
• Caused by GREM1 or BMPR1A gene mutations (autosomal dominant) 1
• Presents with hyperplastic and adenomatous polyps 1

Clinical Recognition Pitfalls

Key diagnostic considerations:

• FAP/AFAP patients with gastric polyps will have cystic fundic gland polyps as the hallmark gastric finding alongside adenomatous polyps 1
• PJS mucocutaneous pigmentation may fade with age and be absent in adults, so absence does not exclude diagnosis 1
• JPS gastric polyps specifically confer 21% gastric cancer risk, making surveillance critical 1
• Solitary juvenile polyps in children are common and not associated with cancer risk, unlike syndromic juvenile polyposis 1
• SMAD4 mutations in JPS require evaluation for HHT-related vascular malformations 1