What are the key clinical features that suggest a diagnosis of Lynch Syndrome in a patient?

Key clinical features suggesting a diagnosis of Lynch syndrome include:

• Early-onset colorectal cancer, typically diagnosed before age 50, often with a family history of colorectal or related cancers on the same side of the family.
• Presence of multiple colorectal cancers or synchronous/metachronous tumours in the patient or relatives.
• Family history of Lynch syndrome-associated cancers such as endometrial cancer, ovarian cancer, gastric, small bowel, urinary tract, and certain other cancers, especially if diagnosed at a young age.
• Mismatch repair (MMR) deficiency in tumour tissue, identified by immunohistochemistry or microsatellite instability testing, indicating pathogenic variants in MMR genes (MLH1, MSH2, MSH6, PMS2).
• Personal or family history of endometrial cancer, particularly at a young age, which is a common extracolonic manifestation of Lynch syndrome.
• Ovarian cancer associated with Lynch syndrome often presents at a younger age and may be linked to MMR gene mutations.

These features collectively raise suspicion for Lynch syndrome and warrant genetic counselling and testing for pathogenic variants in MMR genes to confirm diagnosis and guide management.

This integrated clinical picture is supported by UK guidelines emphasizing family history patterns and tumour MMR status ¹,², and recent literature highlighting the spectrum of Lynch syndrome-associated cancers including endometrial and ovarian cancers (Zhao et al., 2022; Ran et al., 2022; Valle and Monahan, 2024).