Turcot Syndrome

Excerpt

Turcot syndrome (TS) is the association of primary brain tumors to colorectal cancer. Various definitions of Turcot (pronounced with a silent "t," i.e., Turc-oh) syndrome were proposed over the years. Jacques Turcot, a Canadian surgeon, who was among the first to draw attention to the syndrome, defined it as colorectal cancer (CRC) with primary brain tumors. He observed the syndrome in teenage siblings, who presented with a few polyps in the colon, followed by a primary central nervous system (CNS) tumor (a medulloblastoma and a pituitary adenoma, in his case). They had no family history of the syndrome, but their parents were third cousins, leading to the thought that it may be an inherited autosomal recessive disease. Upon genetic analysis of these siblings in 1995 by Hamilton et al., a biallelic mismatch repair (MMR) gene mutation was found. It is now well-known that the coupling of CRC and brain tumors can present secondary to several different genotypes.

There have been attempts to reclassify TS as mismatch repair cancer syndrome (MMRCS) or rename it as brain-tumor polyposis syndrome 1 and 2 (BTPS1 and BTPS2). These syndromes suggest a focus on defining the syndrome by the genetic presentation, involving findings in addition to CRC and primary brain tumors, such as cafe-au-lait spots, hematologic malignancies, among others. However, the original definition of TS is restricted to the phenotypic presentation of solely CRC plus primary brain tumors. Thus, it is now common to see TS1 and TS2, meaning CRC with primary CNS tumor secondary to either MMR gene mutations or APC gene mutations, respectively. In addition, BTPS is commonly used as a synonym to TS today, though BTPS is an expanded version that includes additional symptoms mentioned in this paper.

Hereditary non-polyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) are the 2 most well-known inherited colorectal cancers. HNPCC is associated with mismatch repair (MMR) gene mutations. FAP is associated with an APC gene mutation. HNPCC is generally associated with Lynch syndrome. Gardner syndrome is associated with FAP. If a brain tumor arises in a patient with either HNPCC or FAP, then the patient is considered to have TS1 or TS2, respectively. However, the association with either of these inherited mutations is not necessary.