Báo cáo khoa học: Lynch syndrome: still not a familiar picture

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Lynch syndrome: still not a familiar picture
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Báo cáo khoa học: "Lynch syndrome: still not a familiar picture"World Journal of Surgical Oncology BioMed Central Open AccessCase reportLynch syndrome: still not a familiar pictureFrederik J HesAddress: Center for Human and Clinical Genetics (CHKG), Department of Clinical Genetics, Leiden University Medical Center (LUMC), RCLeiden, The NetherlandsEmail: Frederik J Hes - f.j.hes@lumc.nlPublished: 20 February 2008 Received: 18 December 2007 Accepted: 20 February 2008World Journal of Surgical Oncology 2008, 6:21 doi:10.1186/1477-7819-6-21This article is available from: http://www.wjso.com/content/6/1/21© 2008 Hes; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Germ line mutations in mismatch repair genes underlie Lynch syndrome and predispose carriers for colorectal carcinoma and malignancies in many other organ systems. Case presentation: A large Lynch syndrome family with 15 affected family members and involvement in 7 organs is reported. It illustrates a lack of awareness and knowledge about this hereditary tumor syndrome among doctors as well as patients. None of the described family members underwent presymptomatic screening on the basis of the family history. Conclusion: Hereditary features, like young age at diagnosis, multiple tumors in multiple organs and a positive family history, should lead to timely referral of suspected cases for genetic counseling and diagnostics. For Lynch syndrome, these features can be found in the Amsterdam and Bethesda criteria. Subsequently, early identification of mutation carriers might have diminished, at least in part, the high and early morbidity and mortality observed in this family. loss of protein expression of the causative gene can beBackgroundColorectal carcinoma (CRC) is an important cause of can- demonstrated. In order to standardize clinical and basiccer-related death in the Western world. The lifetime risk is research the Amsterdam criteria were first published inabout 5% and is rising [1]. Currently, about 5% of all CRC 1991 and revised in 1999 [3,4]. In 1997, the Bethesdacases can currently be explained by known inherited guidelines were developed to select patients that should betumor syndromes. The most common of the known CRC tested for MSI and IHC. These guidelines were revised inpredisposing syndromes is Lynch syndrome (previously 2004 [5,6]. The revised Amsterdam criteria and Bethesdaalso annotated as hereditary non-polyposis colorectal can- guidelines are shown in Table 1. These guidelines havecer; HNPCC) which is characterized by the development enabled the recognition of vast numbers of affected fami-of CRC, endometrial cancer and various other cancers [2]. lies, and germline mutation analysis of the MMR-genesThis tumor syndrome is caused by a mutation in one of has led to identification of many (asymptomatic) familythe mismatch repair (MMR) genes: MLH1, MSH2, MSH6 members at risk for Lynch syndrome. However, this caseor PMS2. Tumors observed in Lynch syndrome families report illustrates a lack of awareness about this hereditaryare diagnosed at an unusual early age and may be multi- tumor syndrome among doctors as well as patients.ple. The MMR-defect leads to instability at microsatellitesof tumor-DNA that is called microsatellite instability Case presentation(MSI). Subsequently, with immunohistochemical (IHC-) In November 2006, a 56-year old woman (III-1 in pedi-analysis using antibodies against the four MMR-proteins, gree, Figure 1) visited our clinic for genetic counseling ...