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Lynch syndrome 4(LYNCH4)

MedGen UID:
325005
Concept ID:
C1838333
Disease or Syndrome
Synonyms: Colorectal cancer, hereditary nonpolyposis, type 4; Hereditary non-polyposis colorectal cancer, type 4; LYNCH4
 
Gene (location): PMS2 (7p22.1)
 
Monarch Initiative: MONDO:0013699
OMIM®: 614337

Definition

Lynch syndrome-4 (LYNCH4), or hereditary nonpolyposis colorectal cancer type 4 (HNPCC4), is an autosomal dominant disorder characterized primarily by the development of early-onset colorectal cancer. It is associated with the development of a variety of epithelial tumors that include endometrial cancer, stomach cancer, and ovarian cancer (summary by Thompson et al., 2004). [from OMIM]

Additional description

From MedlinePlus Genetics
People with Lynch syndrome may occasionally have noncancerous (benign) growths in the colon, called colon polyps. In individuals with this disorder, colon polyps occur at a younger age but not in greater numbers than they do in the general population.

Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. People with Lynch syndrome also have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, urinary tract, brain, and skin. Additionally, women with this disorder have a high risk of cancer of the ovaries and lining of the uterus (endometrial cancer). Women with Lynch syndrome have a higher overall risk of developing cancer than men with the condition because of these cancers of the female reproductive system. In individuals with Lynch syndrome who develop cancer, the cancer typically occurs in their forties or fifties.  https://medlineplus.gov/genetics/condition/lynch-syndrome

Clinical features

From HPO
Ovarian neoplasm
MedGen UID:
181539
Concept ID:
C0919267
Neoplastic Process
A tumor (abnormal growth of tissue) of the ovary.
Endometrial carcinoma
MedGen UID:
96903
Concept ID:
C0476089
Neoplastic Process
A carcinoma of the endometrium, the mucous lining of the uterus.
Hereditary nonpolyposis colorectal carcinoma
MedGen UID:
870541
Concept ID:
C4024989
Neoplastic Process

Professional guidelines

PubMed

Taieb J, Svrcek M, Cohen R, Basile D, Tougeron D, Phelip JM
Eur J Cancer 2022 Nov;175:136-157. Epub 2022 Sep 14 doi: 10.1016/j.ejca.2022.07.020. PMID: 36115290
Kurland G, Deterding RR, Hagood JS, Young LR, Brody AS, Castile RG, Dell S, Fan LL, Hamvas A, Hilman BC, Langston C, Nogee LM, Redding GJ; American Thoracic Society Committee on Childhood Interstitial Lung Disease (chILD) and the chILD Research Network
Am J Respir Crit Care Med 2013 Aug 1;188(3):376-94. doi: 10.1164/rccm.201305-0923ST. PMID: 23905526Free PMC Article
Hewish M, Lord CJ, Martin SA, Cunningham D, Ashworth A
Nat Rev Clin Oncol 2010 Apr;7(4):197-208. Epub 2010 Feb 23 doi: 10.1038/nrclinonc.2010.18. PMID: 20177404

Curated

UK NICE Guideline NG151, Colorectal cancer, 2021

UK NICE Diagnostics Guidance DG42, Testing strategies for Lynch syndrome in people with endometrial cancer, 2020

American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, MLH1, MSH2, MSH6, PMS2, EPCAM Pathogenic Variants, Lynch Syndrome (Hereditary Non-polyposis Colon Cancer [HNPCC]), 2019

Recent clinical studies

Etiology

Maratt JK, Stoffel E
Gastrointest Endosc Clin N Am 2022 Jan;32(1):45-58. doi: 10.1016/j.giec.2021.09.002. PMID: 34798986
Bateman AC
J Clin Pathol 2021 Apr;74(4):264-268. Epub 2021 Feb 17 doi: 10.1136/jclinpath-2020-207281. PMID: 33597222
Hammoudi N, Dhooge M, Coriat R, Leblanc S, Barret M, Bordacahar B, Beuvon F, Prat F, Maksimovic F, Chaussade S
Dig Liver Dis 2019 Feb;51(2):299-303. Epub 2018 Oct 15 doi: 10.1016/j.dld.2018.10.005. PMID: 30448460
Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S
Gastroenterology 2015 Sep;149(3):604-13.e20. Epub 2015 May 14 doi: 10.1053/j.gastro.2015.05.006. PMID: 25980754Free PMC Article
Barrow E, Hill J, Evans DG
Fam Cancer 2013 Jun;12(2):229-40. doi: 10.1007/s10689-013-9615-1. PMID: 23604856

Diagnosis

Eikenboom EL, Moen S, van Leeuwen L, Geurts-Giele WRR, Tops CMJ, van Ham TJ, Dinjens WNM, Dubbink HJ, Spaander MCW, Wagner A
HGG Adv 2023 Jan 12;4(1):100167. Epub 2022 Dec 14 doi: 10.1016/j.xhgg.2022.100167. PMID: 36624813Free PMC Article
Maratt JK, Stoffel E
Gastrointest Endosc Clin N Am 2022 Jan;32(1):45-58. doi: 10.1016/j.giec.2021.09.002. PMID: 34798986
Ahadova A, Seppälä TT, Engel C, Gallon R, Burn J, Holinski-Feder E, Steinke-Lange V, Möslein G, Nielsen M, Ten Broeke SW, Laghi L, Dominguez-Valentin M, Capella G, Macrae F, Scott R, Hüneburg R, Nattermann J, Hoffmeister M, Brenner H, Bläker H, von Knebel Doeberitz M, Sampson JR, Vasen H, Mecklin JP, Møller P, Kloor M
Int J Cancer 2021 Feb 15;148(4):800-811. Epub 2020 Aug 3 doi: 10.1002/ijc.33224. PMID: 32683684
Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S
Gastroenterology 2015 Sep;149(3):604-13.e20. Epub 2015 May 14 doi: 10.1053/j.gastro.2015.05.006. PMID: 25980754Free PMC Article
Lynch HT, Smyrk T, Watson P, Lanspa SJ, Boman BM, Lynch PM, Lynch JF, Cavalieri J
Semin Oncol 1991 Aug;18(4):337-66. PMID: 1677781

Therapy

Schjørring OL, Klitgaard TL, Perner A, Wetterslev J, Lange T, Siegemund M, Bäcklund M, Keus F, Laake JH, Morgan M, Thormar KM, Rosborg SA, Bisgaard J, Erntgaard AES, Lynnerup AH, Pedersen RL, Crescioli E, Gielstrup TC, Behzadi MT, Poulsen LM, Estrup S, Laigaard JP, Andersen C, Mortensen CB, Brand BA, White J, Jarnvig IL, Møller MH, Quist L, Bestle MH, Schønemann-Lund M, Kamper MK, Hindborg M, Hollinger A, Gebhard CE, Zellweger N, Meyhoff CS, Hjort M, Bech LK, Grøfte T, Bundgaard H, Østergaard LHM, Thyø MA, Hildebrandt T, Uslu B, Sølling CG, Møller-Nielsen N, Brøchner AC, Borup M, Okkonen M, Dieperink W, Pedersen UG, Andreasen AS, Buus L, Aslam TN, Winding RR, Schefold JC, Thorup SB, Iversen SA, Engstrøm J, Kjær MN, Rasmussen BS; HOT-ICU Investigators
N Engl J Med 2021 Apr 8;384(14):1301-1311. Epub 2021 Jan 20 doi: 10.1056/NEJMoa2032510. PMID: 33471452
Cohen R, Cervera P, Svrcek M, Pellat A, Dreyer C, de Gramont A, André T
Curr Treat Options Oncol 2017 Feb;18(2):9. doi: 10.1007/s11864-017-0453-5. PMID: 28214977
Li SKH, Martin A
Trends Mol Med 2016 Apr;22(4):274-289. Epub 2016 Mar 9 doi: 10.1016/j.molmed.2016.02.003. PMID: 26970951
Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group
JAMA 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. PMID: 26903337
Burn J, Mathers JC, Bishop DT
Fam Cancer 2013 Dec;12(4):707-18. doi: 10.1007/s10689-013-9650-y. PMID: 23880960

Prognosis

Maratt JK, Stoffel E
Gastrointest Endosc Clin N Am 2022 Jan;32(1):45-58. doi: 10.1016/j.giec.2021.09.002. PMID: 34798986
Bateman AC
J Clin Pathol 2021 Apr;74(4):264-268. Epub 2021 Feb 17 doi: 10.1136/jclinpath-2020-207281. PMID: 33597222
Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group
JAMA 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. PMID: 26903337
Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S
Gastroenterology 2015 Sep;149(3):604-13.e20. Epub 2015 May 14 doi: 10.1053/j.gastro.2015.05.006. PMID: 25980754Free PMC Article
Gallion HH, Smith SA
Semin Surg Oncol 1994 Jul-Aug;10(4):249-54. doi: 10.1002/ssu.2980100404. PMID: 8091066

Clinical prediction guides

Maratt JK, Stoffel E
Gastrointest Endosc Clin N Am 2022 Jan;32(1):45-58. doi: 10.1016/j.giec.2021.09.002. PMID: 34798986
Borden LE, Locklear TM, Grider DJ, Osborne JL, Saks EJ, Valea FA, Iglesias DA
Am J Clin Pathol 2022 Jan 6;157(1):90-97. doi: 10.1093/ajcp/aqab100. PMID: 34463332
Bateman AC
J Clin Pathol 2021 Apr;74(4):264-268. Epub 2021 Feb 17 doi: 10.1136/jclinpath-2020-207281. PMID: 33597222
Shiraliyeva N, Friedrichs J, Buettner R, Friedrichs N
Pathol Res Pract 2017 Dec;213(12):1552-1555. Epub 2017 Sep 18 doi: 10.1016/j.prp.2017.09.012. PMID: 29033182
Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S
Gastroenterology 2015 Sep;149(3):604-13.e20. Epub 2015 May 14 doi: 10.1053/j.gastro.2015.05.006. PMID: 25980754Free PMC Article

Recent systematic reviews

Lyons S, Trépel D, Lynch T, Walsh R, O'Dowd S
J Neurol 2023 Sep;270(9):4451-4465. Epub 2023 Jun 8 doi: 10.1007/s00415-023-11791-2. PMID: 37289323Free PMC Article
Eikenboom EL, Moen S, van Leeuwen L, Geurts-Giele WRR, Tops CMJ, van Ham TJ, Dinjens WNM, Dubbink HJ, Spaander MCW, Wagner A
HGG Adv 2023 Jan 12;4(1):100167. Epub 2022 Dec 14 doi: 10.1016/j.xhgg.2022.100167. PMID: 36624813Free PMC Article
Rasmussen M, Madsen MG, Therkildsen C
Urology 2022 Jul;165:44-53. Epub 2022 Feb 22 doi: 10.1016/j.urology.2022.02.006. PMID: 35217028
Anele CC, Adegbola SO, Askari A, Rajendran A, Clark SK, Latchford A, Faiz OD
Colorectal Dis 2017 Jun;19(6):528-536. doi: 10.1111/codi.13679. PMID: 28407411
Sharaf RN, Myer P, Stave CD, Diamond LC, Ladabaum U
Clin Gastroenterol Hepatol 2013 Sep;11(9):1093-100. Epub 2013 May 10 doi: 10.1016/j.cgh.2013.04.044. PMID: 23669308

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NICE, 2021
      UK NICE Guideline NG151, Colorectal cancer, 2021
    • NICE, 2020
      UK NICE Diagnostics Guidance DG42, Testing strategies for Lynch syndrome in people with endometrial cancer, 2020
    • ACMG ACT, 2019
      American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, MLH1, MSH2, MSH6, PMS2, EPCAM Pathogenic Variants, Lynch Syndrome (Hereditary Non-polyposis Colon Cancer [HNPCC]), 2019

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