Key words: MutY human homo- logue(MUTYH),familialadenomatous polyposis, colorectal cancer, hyper- plastic polyposis syndrome, serrated adenoma. Financial disclosure and conflict of interest statement: The authors have no financial disclosures to make or conflictsofinteresttodeclare. Correspondence to: Luigi Zorcolo, MD, Department of General Surgery, Colorectal Unit, University of Cagliari, Policlinico Universitario Monserrato, 09100Cagliari,Italy. Tel+39-070-51096457; fax +39-070-51096438; e-mail gizorcolo@hotmail.com Received December 22, 2010; acceptedMarch4,2011. MUTYH-associated colon disease: adenomatous polyposis is only one of the possible phenotypes. A family report and literature review Luigi Zorcolo 1 , Giovanni Fantola 1 , Luisa Balestrino 2 , Angelo Restivo 1 , Caterina Vivanet 2 , Francesca Spina 2 , Francesco Cabras 1 , Rossano Ambu 3 , and Giuseppe Casula 1 1 Department of General Surgery, Colorectal Unit, University of Cagliari, Cagliari; 2 Genetic Unit, Binaghi Hospital, Cagliari; 3 Department of Pathology, University of Cagliari, Cagliari, Italy ABSTRACT Aims and background. The MutY human homologue gene (MUTYH) is responsible for about a quarter of attenuated familial adenomatous polyposis. Occasionally, it has been associated with hyperplastic polyps and serrated adenoma. We report a family where the same MUTYH mutation determined four different phenotypes, including a case of hyperplastic polyposis syndrome. Patients and methods. A family with a history of right-sided colon cancer and multi- ple colonic polyposis was investigated. Genetic tests were correlated with clinical findings to define phenotypic manifestations of MUTYH mutations. The pertinent English-language literature was reviewed to evaluate the risk of malignancy of MU- TYH and the role of prophylactic surgery. Results. Three male siblings carried a biallelic MUTYH mutation (G382D-exon13), while the fourth was heterozygote. One developed an isolated cecal cancer at the age of 48. Another, aged 38, was diagnosed with numerous minute colonic and rectal polyps and underwent a proctocolectomy, with final pathology showing a picture of hyperplastic and lymphoid polyposis. The third biallelic brother, 46 years old, devel- oped four hyperplastic lesions, while the heterozygote brother had a large flat serrat- ed adenoma of the right colon removed at the age of 50. Conclusion. Many aspects of MUTYH mutation still need to be clarified and one of them regards the different phenotypic expressions. Although the majority of reported cases manifested attenuated adenomatous polyposis, hyperplastic polyps and serrat- ed adenomas appear to be more common than expected. Presenting hyperplastic polyposis syndrome is very unusual and may represent a clinical dilemma for correct management. Current evidence suggests to handle MUTYH-associated polyposis as typical FAP. Introduction Colorectal polyposis is often the expression of an inherited disorder and is consid- ered a predisposition to the development of colorectal cancer (CRC). The classic form is familial adenomatous polyposis (FAP), a well described syndrome characterized by multiple adenomatous lesions which usually appear in the second and third decades of life. The probability of malignant transformation of one of the polyps is close to 100% and thus prophylactic surgery is recommended 1 . A subset of patients present an attenuated form (AFAP) characterized by fewer lesions (<100), a later age of onset, and a predilection for the proximal colon. The genetic basis of FAP is a germline mutation of the adenomatous polyposis coli (APC) gene on chromosome 5 (5q21-q22) 2 . However, only about 10-15% of AFAP cas- es are secondary to APC. More frequently, i.e., in 20-30% of cases 3-5 , this condition has Tumori, 97: 676-680, 2011 © Il Pensiero Scientifico Editore downloaded by IP 216.165.126.139 Thu, 05 Jul 2012, 11:48:03