Lynch syndrome: further defining the pediatric spectrum

Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome defined molecularly by the presence of a pathogenic heterozygous variant in one of the mismatch repair genes: MLH1, MSH2, MSH6, PMS2, or EPCAM. The incidence of LS in the general population is estimated at 1 in 279, with an even higher incidence in those with colorectal cancer and endometrial cancer, the two most common Lynch-associated cancers. Lynch syndrome is currently considered an "adult onset" cancer predisposition syndrome, with the majority of malignancies appearing in adulthood, and recommended screening beginning in adulthood. At present, expert guidelines discourage testing minors for Lynch syndrome. We report seven cases in which children presented with LS and pediatric malignancy, suggesting possible association of childhood onset of cancers with monoallelic mismatch repair deficiency.