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FAMILIAL ADENOMATOUS POLYPOSIS 2; FAP2

FAMILIAL ADENOMATOUS POLYPOSIS 2; FAP2

Alternative titles; symbolsCOLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVEADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE▼ DescriptionAutosomal recessiv...

Alternative titles; symbols

  • COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE
  • ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE

▼ Description
Autosomal recessive colorectal adenomatous polyposis is a disorder characterized by adult-onset of multiple colorectal adenomas and adenomatous polyposis. Affected individuals have a significantly increased risk of colorectal cancer (summary by Sieber et al., 2003).

Cheadle and Sampson (2003) reviewed the molecular pathology and biochemistry of MYH colonic polyposis.

For a discussion of genetic heterogeneity of FAP, see 175100.

▼ Clinical Features
Autosomal recessive FAP is characterized by multiple colorectal adenomas and a high risk of colorectal cancer (summary by Sampson et al., 2003).

Clinical Variability

A combination of pilomatricomas (132600) and adenomatous polyposis coli as an autosomal recessive trait has been reported with mutation in the MYH gene (604933.0008) (Baglioni et al., 2005).

Barnetson et al. (2007) reported a patient with endometrial adenocarcinoma (see 608089) and sebaceous carcinoma of the face who was compound heterozygous for 2 common mutations in the MUTYH gene (Y165C; 604933.0001 and G382D; 604933.0002). Colonic adenomas were not reported, but a paternal aunt reportedly had colorectal cancer in her thirties. Barnetson et al. (2007) noted that the phenotype associated with biallelic MUTYH mutations may include extracolonic manifestations, including endometrial cancer and sebaceous carcinoma, as seen in other inherited colorectal cancer syndromes such as Muir-Torre syndrome (158320) and Lynch syndrome (120435).

▼ Inheritance
Among 614 families recorded in 6 regional registers of polyposis in the UK, Sampson et al. (2003) identified 111 with neither dominant transmission nor evidence of APC mutation. Molecular genetic analysis showed that 25 had biallelic mutations of the MYH gene. The data showed that MYH polyposis can be transmitted as an autosomal recessive trait, requiring a change in genetic counseling, testing, and surveillance. Sampson et al. (2003) recommended that genetic analysis of MYH be offered to patients with a phenotype resembling FAP or attenuated FAP when no clear evidence of vertical transmission is recorded. Further studies were considered necessary to clarify the risk of colorectal cancer for MYH heterozygous individuals.

▼ Molecular Genetics
Al-Tassan et al. (2002) studied a British family in which 3 sibs had multiple colorectal adenomas and carcinoma. There was no clear pathogenic change in the APC gene. Analysis of the MYH gene showed that the sibs were compound heterozygous for nonconservative missense variants (604933.0001-604933.0002).

Jones et al. (2002) and Sieber et al. (2003) also identified biallelic MYH mutations in patients with multiple colorectal adenomas.

Rouleau et al. (2011) reported a 45-year-old French man who was found to have 25 colorectal adenomas on colonoscopy. He had no family history of the disorder. Analysis of the APC gene was negative, and molecular analysis identified compound heterozygosity for mutations in the MUTYH gene: a missense mutation (604933.0002) and a large rearrangement resulting in the deletion of exons 3 to 16 (604933.0009).

Tags: 1p34.1