Muir-Torre Syndrome and founder mismatch repair gene mutations: A long gone historical genetic challenge.

A "cancer predisposing syndrome" later labeled as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Lynch Syndrome, was firstly described by Warthin, about one century ago. An increased predisposition to the development of multiple familial tumors is described as characteristic of this syndrome where visceral and cutaneous malignancies may appear at an early age namely endometrial, gastric, small bowel, ureteral and renal pelvis, ovarian, hepatobiliary tract, pancreatic, brain (Turcot Syndrome) and sebaceous glands (Muir-Torre Syndrome). The latter, a variant of Lynch Syndrome, is characterized by the presence of sebaceous skin adenomas, carcinomas and/or keratoacanthomas associated with visceral malignancies. Both Lynch Syndrome and Muir-Torre Syndrome have been recognized due to germline mutations in mismatch repair genes MLH1, MSH2 and MSH6. To date, 56 Lynch Syndrome founder mutations dependent on MLH1, MSH2 and, although less frequently found, MSH6 and PMS2 are described. Some of these founder mutations, principally of MSH2 gene, have been described to cause Muir-Torre phenotype and have been traced in large and outbreed Muir-Torre Syndrome families living in different US and European territories. Due to the evidences of highly specific Muir-Torre phenotypes related to the presence of widespread MSH2 founder mutations, preliminary search for these MSH2 common mutations in individuals carrying sebaceous tumors and/or keratoacanthomas, at early age or in association to visceral and familial tumors, permits cost-effective and time-saving diagnostic strategies for Lynch/Muir-Torre Syndromes.

Ponti G ，Manfredini M ，Tomasi A ，Pellacani G ... -  《-》

Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population.

Lagerstedt-Robinson K ，Rohlin A ，Aravidis C ，Melin B ，Nordling M ，Stenmark-Askmalm M ，Lindblom A ，Nilbert M ... -  《-》

Value of MLH1 and MSH2 mutations in the appearance of Muir-Torre syndrome phenotype in HNPCC patients presenting sebaceous gland tumors or keratoacanthomas.

Ponti G ，Losi L ，Pedroni M ，Lucci-Cordisco E ，Di Gregorio C ，Pellacani G ，Seidenari S ... -  《JOURNAL OF INVESTIGATIVE DERMATOLOGY》

The frequency of Muir-Torre syndrome among Lynch syndrome families.

South CD ，Hampel H ，Comeras I ，Westman JA ，Frankel WL ，de la Chapelle A ... -  《-》

[Muir-Torre syndrome and Turcot syndrome].

Lynch syndrome (LS) is a syndrome that carries a genetic predisposition to certain cancers associating, either in a single individual or in a family, a visceral tumour, mainly colorectal, with a high risk of other synchronous or metachronous cancers. LS is linked with mutations in the genes coding for proteins in the DNA repair system. Phenotypic variants of SL exist, including Muir-Torre syndrome (MTS) and Turcot syndrome (TS), both of which predispose to colorectal cancer. They may be distinguished by the presence of benign or malignant sebaceous tumours in MTS, and tumours of the central nervous system in TS. A 59-year-old man, with a history of right colon cancer at the age of 36 years, consulted for a nose lesion shown by histopathological examination to be a sebaceous tumour. Immunohistochemistry revealed loss of expression of proteins MSH2 and MSH6, strongly suggesting a diagnosis of MTS. Eight years earlier, the man's son had developed a fatal glioblastoma; given the paternal phenotype of MTS, the hypothesis of TS in the son is probable. This case suggests that several variants of Lynch syndrome may be seen within the same family. It raises the issue of screening for cerebral tumours in patients with MTS and in their family members, even though such a recommendation does not exist; current recommendations in fact consist primarily of gastrointestinal and gynaecological monitoring.

Velter C ，Caussade P ，Fricker JP ，Cribier B ... -  《ANNALES DE DERMATOLOGIE ET DE VENEREOLOGIE》