Definition

Lynch syndrome is a cancer predisposition syndrome caused by hereditary variants in DNA mismatch repair (MMR) genes, primarily MLH1, MSH2, MSH6, PMS2, and EPCAM. The MLH1 protein is part of the MMR complex that corrects errors arising during DNA replication; MLH1 variants account for approximately 40% of Lynch syndrome diagnoses. Loss of function leads to accumulation of repair errors in the cell and microsatellite instability, the characteristic molecular signature of Lynch related tumors. Colorectal and endometrial cancer are the most common cancers in individuals with Lynch syndrome; these cancers typically develop at an earlier age than the population average.

Gene/region examined

MLH1 - Whole gene

Method

Sequence analysis

Accepted sample types

EDTA blood, AF, CVS

Inheritance

Autosomal dominant; a pathogenic variant in one copy of the gene is sufficient for predisposition, with a 50% chance of transmission from an affected parent to a child in each pregnancy.

Related Tests

Inheritance Patterns

Describes how a genetic condition is passed on within a family. There are five main patterns

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Carrier (Heterozygous / Homozygous)

Why it matters: In autosomal recessive inheritance, when each parent is a carrier (while both appear healthy), the chance of their child being born with the disease is 25% in each

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VUS (Variant of Uncertain Significance)

This is the situation where the test has detected a change in the DNA, but the role of this change in the development of disease is unconfirmed.

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How to Read a Genetic Test Result (Positive / Negative / VUS)

A genetic test result falls into three main categories

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Types of Genetic Tests

A genetic test is a type of medical test that detects changes in genes, chromosomes or proteins. Today there are more than 77,000 genetic tests available.

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