MUTYH-Associated Polyposis – Definition
MUTYH-associated polyposis (MAP, OMIM #608456) is a genetic disease caused by a biallelic mutation in the MUTYH gene that predisposes to colorectal carcinoma. Carcinomas and commonly occurring adenomatous colon polyps (between 10 and a few hundred) generally do not appear until adulthood. In addition, there is also an increased risk of developing duodenal polyps and a duodenal carcinoma. Extraintestinal manifestations are possible as well.
Synonyms:
Familial adenomatous polyposis 2 (FAP2)
Colorectal adenomatous polyposis, autosomal recessive
Multiple colorectal adenomas, autosomal recessive
Gene:
MUTYH
Gene product:
MUTYH
Function:
Adenine-DNA glycosylase, a DNA repair enzyme (base excision repair)
A defect leads to an accumulation of G:C>T:A transversions, resulting in a stop codon in the mRNA following replication and, thus, to a protein malfunction.
Pattern of inheritance:
Autosomal recessive
Prevalence:
1-2% of the population in Northern Europe is heterozygous for a MUTYH mutation.
The prevalence of biallelic MUTYH mutations is around 1:20,000-1:40,000.
Genotype-phenotype correlation:
Patients with a homozygous c.536A>G mutation have a greater risk of a severe disease progression and early onset (around 8 years earlier) of the disease than patients with a homozygous mc.1187G>A mutation.
Penetrance:
High for colorectal carcinoma, but incomplete (lifetime risk 43-100%)
Unknown for colorectal polyps, but probably incomplete (around one third of patients with colorectal carcinoma do not present with any polyps)
MUTYH-Associated Polyposis – Diagnosis

Suspected Diagnosis
MUTYH-associated polyposis is suspected if the following findings are present:
Clinical:
- Colon adenomas and/or hyperplastic/serrated sessile polyps in a number of:
- 1-10 (aged <40 years)
- 10 (aged 40-60 years)
- 20 (aged >60 years)
- 20 to several hundred colon adenomas and/or hyperplastic/serrated sessile polyps
- Polyposis coli (e.g. >100 colonic polyps) without heterozygous APC germline mutation
- Colorectal carcinoma at an age <40 years
- Positive family history of colon cancer (± polyps) compatible with autosomal recessive inheritance
Histological/Molecular Genetic:
- Somatic KRAS mutation in colorectal carcinoma
- Microsatellite instability in colorectal carcinoma
Genetic Diagnostics
The diagnosis of “MUTYH-associated polyposis” is confirmed by detecting a biallelic mutation of the MUTYH gene by sequence analysis and, if necessary, subsequent deletion/duplication analysis. Panel examinations, in which several genes are recorded, can also be helpful.
Differential Diagnoses
- APC-Associated Adenomatous Polyposis
- NTHL1-Associated Polyposis
- Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC), also known as Lynch syndrome
- Peutz-Jeghers Syndrome
- Juvenile Polyposis Syndrome
- PTEN Hamartoma Tumor Syndrome, also known as Cowden syndrome
- Hereditary Mixed Polyposis Syndrome
- Serrated Polyposis Syndrome
Clinical Presentation

Colon Polyps
The number of colon polyps in patients with the MUTYH mutation is usually between ten and several hundred. These occur on average at the age of 50, rarely before the age of 30, and can be classic or serrated adenomas, hyperplastic/serrated sessile, or mixed (hyperplastic and adenomatous) polyps.
Colon Carcinoma
If no early detection measures are carried out, the lifetime risk of developing colorectal cancer is between 43% and 100%. The majority of carcinomas only develop in adulthood, which means that the risk of developing colon carcinoma in childhood and adolescence is extremely low.
Duodenal Polyps and Duodenal Carcinoma
Duodenal polyps are found in 17-25% of patients with the MUTYH mutation. The lifetime risk of duodenal carcinoma is around 4%.
Gastric Fundus Polyps and Gastric Carcinoma
In 11% of MAP patients, lesions were detected during gastroscopies as part of early detection.
Extraintestinal Manifestations
The incidence of extraintestinal malignancies is about twice as high in individuals with the MUTYH mutation as in the general population. Extraintestinal manifestations described to date are as follows:
- Ovarian, bladder, breast, endometrial carcinoma
- Skin: Benign and malignant tumors of the sebaceous glands, melanoma, squamous cell carcinoma, basal cell carcinoma, benign skin tumors
- Thyroid gland: thyroid carcinoma, multinodular goiter, singular thyroid nodules
- Jaw cysts
Special Features of Treatment

A polypectomy should be performed for suspicious colonic polyps. A subtotal colectomy or proctocolectomy should be considered if there is a large number and high density of polyps. Similar to the treatment of FAP and AFAP, a colectomy is also recommended as soon as adenomas appear. Still, this measure can be delayed depending on the size, histology, and number of adenomatous polyps. If a colorectal carcinoma is diagnosed, a colectomy is unavoidable.
Diagnosis of MUTYH-Associated Polyposis- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Diagnosis of MUTYH-Associated Polyposis- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Recommendations for Early Detection in Your Patients

For Children and Adolescents
No early detection measures are recommended for children and adolescents.
For Adults
- Colonoscopy every 2 years from the age of 18
- Oesophago-gastro-duodenoscopy from 25-30 years of age
As MAP is an autosomal recessive inherited disease, if a person is known to have a MUTYH mutation, a preconception diagnosis of the partner can be considered to assess the risk of their children developing MAP.