Lynch Syndrome: A Pediatric Perspective

abstract

Colorectal cancer is a rare disease in the pediatric age group and when present suggests an underlying genetic predisposition. The most common hereditary colon cancer susceptibility condition, Lynch syndrome, previously known as Hereditary Non-Polyposis Colorectal Cancer is an autosomal dominant condition caused by a germline mutation in one of four DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The mutation prone phenotype of this disorder is associated with gastrointestinal, endometrial and other cancers and is now being identified in both symptomatic adolescents with malignancy as well in asymptomatic mutation carriers who are at risk for a spectrum of gastrointestinal and other cancers later in life. We review the DNA mismatch repair system, our current understanding of Lynch Syndrome in the pediatric population and discuss the newly identified bi-allelic form of the disease known as Constitutional Mismatch Repair Deficiency Syndrome.

Both family history and tumor characteristics can help to identify patients who should undergo genetic testing for these cancer predisposition syndromes. Patients who carry either single allele (Lynch Syndrome) or double allele (Constitutional Mismatch Repair Deficiency Syndrome) mutations in the mismatch repair genes benefit from cancer surveillance programs that target both the digestive and extra-intestinal cancer risk of these diseases. Since spontaneous mutation in any one of the mismatch repair genes is extremely rare, genetic counseling and testing is suggested for all at-risk family members.