title: The gastrointestinal manifestation of constitutional mismatch repair deficiency syndrome: from a single adenoma to polyposis-like phenotype and early onset cancer.
abstract: Data on the clinical presentation of constitutional mismatch repair deficiency syndrome (CMMRD) is accumulating. However, as the extraintestinal manifestations are often fatal and occur at early age, data on the systematic evaluation of the gastrointestinal tract is scarce. Here we describe 11 subjects with verified biallelic carriage and who underwent colonoscopy, upper endoscopy and small bowel evaluation. Five subjects were symptomatic and in six subjects the findings were screen detected. Two subjects had colorectal cancer and few adenomatous polyps (19, 20 years), three subjects had polyposis-like phenotype (13, 14, 16 years), four subjects had few adenomatous polyps (8, 12-14 years) and two subjects had no polyps (both at age 6). Of the three subjects in the polyposis-like group, two subjects had already developed high-grade dysplasia or cancer and one subject had atypical juvenile polyps suggesting juvenile polyposis. Three out of the five subjects that underwent repeated exams had significant findings during short interval. The gastrointestinal manifestations of CMMRD are highly dependent upon age of examination and highly variable. The polyps may also resemble juvenile polyposis. Intensive surveillance according to current guidelines is mandatory.
authors.affiliation: The Early Detection and High Risk GI Cancer Service, the Gastroenterology Division, Rabin Medical Center, Petach Tikva, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Z
authors.initials: Z
authors.lastname: Levi
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Kariv
authors.affiliation: The Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Barnes-Kedar
authors.affiliation: The Sharett Institute for Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Goldberg
authors.affiliation: Gastroenterology Department, Rambam Health Care Campus, Haifa, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Half
authors.affiliation: Pathology Department, Rabin Medical Center, Petach Tikva, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Morgentern
authors.affiliation: Pathology Department, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Eli
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|The Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel.
authors.forename: H N
authors.initials: HN
authors.lastname: Baris
authors.affiliation: The Early Detection and High Risk GI Cancer Service, the Gastroenterology Division, Rabin Medical Center, Petach Tikva, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Vilkin
authors.affiliation: The Early Detection and High Risk GI Cancer Service, the Gastroenterology Division, Rabin Medical Center, Petach Tikva, Israel.
authors.forename: R G
authors.initials: RG
authors.lastname: Belfer
authors.affiliation: The Early Detection and High Risk GI Cancer Service, the Gastroenterology Division, Rabin Medical Center, Petach Tikva, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Niv
authors.affiliation: Pediatric Hemato-Oncology Department, Tel Aviv, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Elhasid
authors.affiliation: The Pediatric Gastroenterology Unit, 'Dana-Dwek' Children's Hospital, Tel Aviv Medical Center, Tel Aviv, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Dvir
authors.affiliation: Gastroenterology Department, Soroka Medical Center, Beersheba, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Abu-Freha
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|The Pediatric Gastroenterology Unit, 'Dana-Dwek' Children's Hospital, Tel Aviv Medical Center, Tel Aviv, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Cohen
mesh_terms: D018256:Adenomatous Polyps / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D018912:Arabs / Q000235:genetics; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D016099:Endoscopy, Gastrointestinal; D005260:Female; D006801:Humans; D044483:Intestinal Polyposis / Q000151:congenital / Q000175:diagnosis / Q000235:genetics; D007585:Jews / Q000235:genetics; D008297:Male; D000070976:Mismatch Repair Endonuclease PMS2; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009386:Neoplastic Syndromes, Hereditary / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes
keywords: Lynch syndrome; biallelic Lynch syndrome; constitutional mismatch repair deficiency syndrome; hereditary non-polyposis colorectal cancer