MUTYH Polyposis

The recessive one — so screen the siblings, not just the children. MUTYH-associated polyposis looks like attenuated FAP on a scope, but it's autosomal recessive, which flips the family risk math. And a single (heterozygous) MUTYH result is not the disease — don't over-screen it. Draft reference — pending Dr. Anderson's clinical sign-off. Cite the primary source, not this page.

What it is

MUTYH-associated polyposis (MAP) is caused by biallelic (two) pathogenic variants in MUTYH, a base-excision-repair gene. Losing it leaves characteristic G:C→T:A errors and produces an attenuated-polyposis picture — ten to a few hundred colorectal adenomas — that clinically overlaps attenuated FAP and Lynch.

Inheritance changes who you screen

Autosomal recessive — the opposite pattern from FAP and Lynch

  • Both parents are obligate carriers — the disease usually appears with no affected parent, so it can look "sporadic."
  • Full siblings carry the real risk: 25% affected, 50% carriers. Siblings are the priority for testing — not the children.
  • Children are usually just carriers — an affected parent passes one variant, so offspring are affected only if the other parent also carries one (~1–2% population frequency).

Contrast the dominant syndromes, where each child has a 50% risk. Here the horizontal (sibling) axis matters more than the vertical (parent→child) one.

Biallelic disease vs carrier — don't conflate them

Biallelic — MUTYH-associated polyposis (MAP) polyposis surveillance
Colorectal risk:
~43–63% by age 60 (observed cumulative incidence); rising toward ~80–90% over a lifetime if left unsurveilled (untreated natural history)
Polyps:
Ten to a few hundred colorectal adenomas (attenuated-polyposis range)
Onset:
Mean colorectal cancer onset ~50 years
Management:
Polyposis-grade surveillance: colonoscopy every 1–2 years from age 25–30 with polypectomy; colectomy once polypectomy can no longer control the burden (or for cancer / symptoms). Duodenal EGD (side-viewing) from age 30–35 (interval by Spigelman). Also elevated: duodenal (~4%), ovarian (~6–14%), and bladder cancer (~6–8% in women, up to ~25% in men).
What to tell the patient:
Explain the surveillance is polyposis-grade — like attenuated FAP — and lifelong. Then make the recessive point: it does not usually pass to the children, but full siblings are at real risk and should be tested.
Note:
Two pathogenic variants (biallelic) cause the disease. Founder variants Y179C (earlier, more severe) and G396D (~8 years later onset) account for most cases in people of European ancestry.

GeneReviews: MUTYH Polyposis (2021).

Monoallelic — heterozygous carrier near-population · screen per family history
Colorectal risk:
Only marginally increased — ~2–3× for late-onset CRC against a ~5.5% population baseline; near-population from the gene alone. Family history — not the carrier result — sets the screening interval.
Polyps:
Not a polyposis phenotype
Management:
Average-to-moderate-risk colorectal screening guided by family history — NOT polyposis surveillance and NOT surgery. A single MUTYH carrier result does not by itself warrant intensive screening.
What to tell the patient:
Reassure: a heterozygous MUTYH result is common and is not the disease. Screening follows family history, not the gene. The real action is reproductive — if planning children, the partner's carrier status is what matters (recessive).
Note:
Carrier, not affected. Population carrier frequency ~1–2%. Matters most for offspring risk when the reproductive partner is also a carrier.

GeneReviews: MUTYH Polyposis (2021).

Where it sits in the polyposis differential

MAP is the recessive member of the same differential the polyposis pages share:

  • MUTYH-associated polyposis — recessive, 10–100+ adenomas, onset ~50.
  • Attenuated FAP — dominant, overlapping polyp count. Because they look alike, test APC and MUTYH together when the polyp count is in the attenuated range.
  • Lynch syndrome — few/no polyps, MMR-deficient / MSI-high tumor.

The family-physician move

  1. Suspect it with 10–100+ adenomas, especially colorectal cancer with no clear dominant family history — MAP looks sporadic.
  2. Refer to genetics; multigene testing covers APC and MUTYH together.
  3. If biallelic → polyposis surveillance (colonoscopy from 25–30, duodenal EGD from 30–35) and prioritize testing the siblings.
  4. If a heterozygous carrier → reassure, screen by family history, and raise partner testing only if childbearing is planned.

See Inheritance & Family History for cascade testing once the family's variants are known.

Source: GeneReviews: MUTYH Polyposis (2021); surveillance per NCCN. Autosomal recessive — siblings of an affected person have a 25% chance of being affected. General education for clinicians, not a substitute for formal genetic counseling.