Gastrointestinal Findings in the Largest Series of Patients With Hereditary Biallelic Mismatch Repair Deficiency Syndrome: Report from the International Consortium

Melyssa Aronson, Steven Gallinger, Zane Cohen, Shlomi Cohen, Rina Dvir, Ronit Elhasid, Hagit N. Baris, Revital Kariv, Harriet Druker, Helen Chan, Simon C. Ling, Paul Kortan, Spring Holter, Kara Semotiuk, David Malkin, Roula Farah, Alain Sayad, Brandie Heald, Matthew F. Kalady, Lynette S. PenneyAndrea L. Rideout, Mohsin Rashid, Linda Hasadsri, Pavel Pichurin, Douglas Riegert-Johnson, Brittany Campbell, Doua Bakry, Hala Al-Rimawi, Qasim Kholaif Alharbi, Musa Alharbi, Ashraf Shamvil, Uri Tabori, Carol Durno

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objectives:Hereditary biallelic mismatch repair deficiency (BMMRD) is caused by biallelic mutations in the mismatch repair (MMR) genes and manifests features of neurofibromatosis type 1, gastrointestinal (GI) polyposis, and GI, brain, and hematological cancers. This is the first study to characterize the GI phenotype in BMMRD using both retrospective and prospective surveillance data.Methods:The International BMMRD Consortium was created to collect information on BMMRD families referred from around the world. All patients had germline biallelic MMR mutations or lack of MMR protein staining in normal and tumor tissue. GI screening data were obtained through medical records with annual updates.Results:Thirty-five individuals from seven countries were identified with BMMRD. GI data were available on 24 of 33 individuals (73%) of screening age, totaling 53 person-years. The youngest age of colonic adenomas was 7, and small bowel adenoma was 11. Eight patients had 19 colorectal adenocarcinomas (CRC; median age 16.7 years, range 8–25), and 11 of 18 (61%) CRC were distal to the splenic flexure. Eleven patients had 15 colorectal surgeries (median 14 years, range 9–25). Four patients had five small bowel adenocarcinomas (SBC; median 18 years, range 11–33). Two CRC and two SBC were detected during surveillance within 6–11 months and 9–16 months, respectively, of last consecutive endoscopy. No patient undergoing surveillance died of a GI malignancy. Familial clustering of GI cancer was observed.Conclusions:The prevalence and penetrance of GI neoplasia in children with BMMRD is high, with rapid development of carcinoma. Colorectal and small bowel surveillance should commence at ages 3–5 and 8 years, respectively.Am J Gastroenterol advance online publication, 5 January 2016; doi:10.1038/ajg.2015.392.

Original languageEnglish (US)
JournalAmerican Journal of Gastroenterology
DOIs
StateAccepted/In press - Jan 5 2016

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DNA Mismatch Repair
Adenoma
Adenocarcinoma
Neoplasms
Transverse Colon
Colorectal Surgery
Mutation
Neurofibromatosis 1
Gastrointestinal Neoplasms
Penetrance
Brain Neoplasms
Endoscopy
Medical Records
Cluster Analysis
Publications
Turcot syndrome
Staining and Labeling
Carcinoma
Phenotype
Genes

ASJC Scopus subject areas

  • Gastroenterology

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Gastrointestinal Findings in the Largest Series of Patients With Hereditary Biallelic Mismatch Repair Deficiency Syndrome : Report from the International Consortium. / Aronson, Melyssa; Gallinger, Steven; Cohen, Zane; Cohen, Shlomi; Dvir, Rina; Elhasid, Ronit; Baris, Hagit N.; Kariv, Revital; Druker, Harriet; Chan, Helen; Ling, Simon C.; Kortan, Paul; Holter, Spring; Semotiuk, Kara; Malkin, David; Farah, Roula; Sayad, Alain; Heald, Brandie; Kalady, Matthew F.; Penney, Lynette S.; Rideout, Andrea L.; Rashid, Mohsin; Hasadsri, Linda; Pichurin, Pavel; Riegert-Johnson, Douglas; Campbell, Brittany; Bakry, Doua; Al-Rimawi, Hala; Alharbi, Qasim Kholaif; Alharbi, Musa; Shamvil, Ashraf; Tabori, Uri; Durno, Carol.

In: American Journal of Gastroenterology, 05.01.2016.

Research output: Contribution to journalArticle

Aronson, M, Gallinger, S, Cohen, Z, Cohen, S, Dvir, R, Elhasid, R, Baris, HN, Kariv, R, Druker, H, Chan, H, Ling, SC, Kortan, P, Holter, S, Semotiuk, K, Malkin, D, Farah, R, Sayad, A, Heald, B, Kalady, MF, Penney, LS, Rideout, AL, Rashid, M, Hasadsri, L, Pichurin, P, Riegert-Johnson, D, Campbell, B, Bakry, D, Al-Rimawi, H, Alharbi, QK, Alharbi, M, Shamvil, A, Tabori, U & Durno, C 2016, 'Gastrointestinal Findings in the Largest Series of Patients With Hereditary Biallelic Mismatch Repair Deficiency Syndrome: Report from the International Consortium', American Journal of Gastroenterology. https://doi.org/10.1038/ajg.2015.392
Aronson, Melyssa ; Gallinger, Steven ; Cohen, Zane ; Cohen, Shlomi ; Dvir, Rina ; Elhasid, Ronit ; Baris, Hagit N. ; Kariv, Revital ; Druker, Harriet ; Chan, Helen ; Ling, Simon C. ; Kortan, Paul ; Holter, Spring ; Semotiuk, Kara ; Malkin, David ; Farah, Roula ; Sayad, Alain ; Heald, Brandie ; Kalady, Matthew F. ; Penney, Lynette S. ; Rideout, Andrea L. ; Rashid, Mohsin ; Hasadsri, Linda ; Pichurin, Pavel ; Riegert-Johnson, Douglas ; Campbell, Brittany ; Bakry, Doua ; Al-Rimawi, Hala ; Alharbi, Qasim Kholaif ; Alharbi, Musa ; Shamvil, Ashraf ; Tabori, Uri ; Durno, Carol. / Gastrointestinal Findings in the Largest Series of Patients With Hereditary Biallelic Mismatch Repair Deficiency Syndrome : Report from the International Consortium. In: American Journal of Gastroenterology. 2016.
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abstract = "Objectives:Hereditary biallelic mismatch repair deficiency (BMMRD) is caused by biallelic mutations in the mismatch repair (MMR) genes and manifests features of neurofibromatosis type 1, gastrointestinal (GI) polyposis, and GI, brain, and hematological cancers. This is the first study to characterize the GI phenotype in BMMRD using both retrospective and prospective surveillance data.Methods:The International BMMRD Consortium was created to collect information on BMMRD families referred from around the world. All patients had germline biallelic MMR mutations or lack of MMR protein staining in normal and tumor tissue. GI screening data were obtained through medical records with annual updates.Results:Thirty-five individuals from seven countries were identified with BMMRD. GI data were available on 24 of 33 individuals (73{\%}) of screening age, totaling 53 person-years. The youngest age of colonic adenomas was 7, and small bowel adenoma was 11. Eight patients had 19 colorectal adenocarcinomas (CRC; median age 16.7 years, range 8–25), and 11 of 18 (61{\%}) CRC were distal to the splenic flexure. Eleven patients had 15 colorectal surgeries (median 14 years, range 9–25). Four patients had five small bowel adenocarcinomas (SBC; median 18 years, range 11–33). Two CRC and two SBC were detected during surveillance within 6–11 months and 9–16 months, respectively, of last consecutive endoscopy. No patient undergoing surveillance died of a GI malignancy. Familial clustering of GI cancer was observed.Conclusions:The prevalence and penetrance of GI neoplasia in children with BMMRD is high, with rapid development of carcinoma. Colorectal and small bowel surveillance should commence at ages 3–5 and 8 years, respectively.Am J Gastroenterol advance online publication, 5 January 2016; doi:10.1038/ajg.2015.392.",
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T2 - Report from the International Consortium

AU - Aronson, Melyssa

AU - Gallinger, Steven

AU - Cohen, Zane

AU - Cohen, Shlomi

AU - Dvir, Rina

AU - Elhasid, Ronit

AU - Baris, Hagit N.

AU - Kariv, Revital

AU - Druker, Harriet

AU - Chan, Helen

AU - Ling, Simon C.

AU - Kortan, Paul

AU - Holter, Spring

AU - Semotiuk, Kara

AU - Malkin, David

AU - Farah, Roula

AU - Sayad, Alain

AU - Heald, Brandie

AU - Kalady, Matthew F.

AU - Penney, Lynette S.

AU - Rideout, Andrea L.

AU - Rashid, Mohsin

AU - Hasadsri, Linda

AU - Pichurin, Pavel

AU - Riegert-Johnson, Douglas

AU - Campbell, Brittany

AU - Bakry, Doua

AU - Al-Rimawi, Hala

AU - Alharbi, Qasim Kholaif

AU - Alharbi, Musa

AU - Shamvil, Ashraf

AU - Tabori, Uri

AU - Durno, Carol

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