Last updated 2mo ago
A 45-year-old presents with iron-deficiency anemia. Colonoscopy reveals 30 adenomatous polyps and a colorectal adenocarcinoma. Family history shows no affected parents but two affected siblings. Genetic testing reveals biallelic MUTYH pathogenic variants.
AR; MUTYH (base excision repair: repairs oxidative DNA damage, specifically 8-oxoguanine)
- Biallelic variants required for full phenotype
- Two common European founder variants: Y179C and G396D
- Monoallelic carriers: modestly increased CRC risk (unclear if clinically actionable)
- Somatic signature: excess G:C→T:A transversions
- 20-100 adenomatous polyps (attenuated polyposis phenotype)
- CRC risk 43-100% without surveillance
- Later onset than classic FAP (typically 40s-50s)
- Duodenal adenomas/cancer risk
- Autosomal recessive: often no family history in parents (horizontal pattern in siblings)
- MUTYH full gene sequencing
- Consider in patients with 10-100 adenomatous polyps, especially if APC-negative
- Consider in early-onset CRC with somatic G:C→T:A signature
- Colonoscopy every 1-2 years starting age 25-30
- Upper endoscopy every 3-5 years for duodenal surveillance
- Colectomy if polyp burden unmanageable by polypectomy
- Genetic counseling for siblings (25% recurrence risk)
MUTYH = base excision repair (BER): You only need to know the "BER" (bare) minimum about BER: MUTYH is the only well-known disease gene for base excision repair.
MAP is the AR polyposis syndrome: Unlike FAP (AD, APC) and Lynch (AD, MMR), MAP requires biallelic variants. No affected parents, horizontal (sibling) pattern: think AR inheritance when you see multiple affected siblings with polyps.