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Muir-Torre syndrome

Patricia Tai, MB, BS, DABR, FRCR, FRCPC
Section Editor
June K Robinson, MD
Deputy Editor
Rosamaria Corona, MD, DSc


Muir-Torre syndrome (MIM #158320) is a rare autosomal dominant condition characterized by the association of at least one sebaceous skin tumor and at least one visceral malignancy [1]. Muir-Torre syndrome is caused by germline mutations in the DNA mismatch repair genes and is considered a phenotypic variant of hereditary nonpolyposis colorectal carcinoma syndrome (HNPCC, Lynch syndrome). Internal malignancies most frequently associated with Muir-Torre syndrome include colorectal, endometrial, ovarian, and urothelial cancers [2,3].

This topic will discuss the pathogenesis, clinical features, diagnosis, and management of Muir-Torre syndrome. Lynch syndrome is discussed separately. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis" and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Screening and management".)


Muir-Torre syndrome is caused by germline mutations in one allele of the DNA mismatch repair (MMR) genes MLH1, MSH2, or MSH6. The MMR system consists of human mutS homolog 2 (hMSH2), human mutS homolog 3 (hMSH3), human mutS homolog 6 (hMSH6), human mutL homolog 1 (hMLH1), and human postmeiotic segregation increased 2 (hPMS2) proteins. They are responsible for maintaining the genomic integrity by correcting base substitution mismatches and small insertion-deletion mismatches generated by errors in base pairing during DNA replication.

Microsatellite instability (MSI) is the hallmark of MMR gene deficiency. Microsatellites are short repetitive DNA sequences, typically mononucleotide or dinucleotide tandem repeats, that are susceptible to mutations during DNA replication. The loss of DNA mismatch repair function due to germline and/or somatic inactivating mutations of MMR genes leads to the accumulation of mutations across the genome and mainly in the microsatellite repetitive sequences, creating a molecular phenotype known as microsatellite instability.

Mutations in MLH1 and MSH2 have the most severe effect, producing a high-frequency MSI phenotype (MSI-H). An MSI-H phenotype can be demonstrated in nearly all cutaneous and visceral tumors from patients with Muir-Torre syndrome [4,5].


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Literature review current through: Sep 2016. | This topic last updated: Mar 15, 2016.
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