Knowledge and perceptions of constitutional mismatch repair deficiency amongst Lynch syndrome carriers

Constitutional mismatch repair deficiency (CMMRD) is a rare childhood cancer predisposition syndrome caused by biallelic pathogenic germline variants in the same Lynch syndrome (LS) gene. Affected individuals have a markedly increased risk of cancer before age 18. The frequency with which adults with LS are counseled about CMMRD and their understanding of the reproductive risk for CMMRD are uncertain. This study evaluated the awareness of CMMRD and the impact of CMMRD risk on reproductive decision-making among adults with LS. An IRB-approved electronic survey was distributed via MyChart to adult LS patients at Penn Medicine’s King Center for Lynch Syndrome, through the King Center’s listserv, and in partnership with the advocacy organization Alive and Kick’n. The survey assessed prior knowledge of CMMRD, its influence on reproductive choices, and the perceived importance of discussing CMMRD risk after LS diagnosis. Responses were analyzed using descriptive and inferential statistics. Among 150 respondents, 29% ( n = 43) reported prior knowledge of CMMRD, of which 81% ( n = 35) learned about CMMRD from healthcare professionals. Other common sources of knowledge included the internet ( n = 13) and support groups ( n = 9). Among participants with biological children, 22% ( n = 25) conceived after their LS diagnosis. Of these, 32% ( n = 8) were aware of CMMRD risk before conception, with 50% ( n = 4) reporting the other biological parent underwent genetic testing prior to conception. Of those unaware of CMMRD prior to conception despite already having an LS diagnosis ( n = 17), 76% ( n = 13) indicated they would have wanted partner testing had they known about CMMRD prior to conception. Among participants planning future biological children, 78% ( n = 11) reported moderate or high concern about CMMRD risk, and 71% ( n = 10) indicated partner testing had occurred or was planned. Among individuals who neither have nor plan biological children, 19% ( n = 4) reported that CMMRD risk influenced their decision. Overall, 65% ( n = 97) rated discussion of CMMRD risk following LS diagnosis as very important. Findings from this study show that knowledge of CMMRD among adults with LS is limited. Participants expressed a strong desire for counseling about CMMRD prior to reproductive decision-making, highlighting the need for improved education and communication about CMMRD by healthcare professionals.