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Mismatch repair cancer syndrome 4(MMRCS4)

MedGen UID:
1745382
Concept ID:
C5436817
Disease or Syndrome
Synonyms: mismatch repair cancer syndrome 4; MMRCS4
 
Gene (location): PMS2 (7p22.1)
 
Monarch Initiative: MONDO:0030843
OMIM®: 619101

Definition

Mismatch repair cancer syndrome-4 (MMRCS4) is an autosomal recessive childhood cancer predisposition syndrome characterized by early-onset leukemia/lymphoma, brain tumors, colorectal/gastrointestinal cancers, and other rare malignancies, including rhabdomyosarcoma (summary by Li et al., 2015). Cafe-au-lait spots are usually present (De Vos et al., 2006). For a discussion of genetic heterogeneity of mismatch repair cancer syndrome, see MMRCS1 (276300). [from OMIM]

Clinical features

From HPO
Non-Hodgkin lymphoma
MedGen UID:
6160
Concept ID:
C0024305
Neoplastic Process
A type of lymphoma characterized microscopically by the absence of multinucleated Reed-Sternberg cells.
Colon cancer
MedGen UID:
2839
Concept ID:
C0007102
Neoplastic Process
A primary or metastatic malignant neoplasm that affects the colon. Representative examples include carcinoma, lymphoma, and sarcoma.
Adenomatous colonic polyposis
MedGen UID:
358118
Concept ID:
C1868071
Finding
Presence of multiple adenomatous polyps in the colon.
Astrocytoma
MedGen UID:
438
Concept ID:
C0004114
Neoplastic Process
Astrocytoma is a neoplasm of the central nervous system derived from astrocytes. Astrocytes are a type of glial cell, and thus astrocytoma is a subtype of glioma.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Gray matter heterotopia
MedGen UID:
452349
Concept ID:
C0266491
Finding
Heterotopia or neuronal heterotopia are macroscopic clusters of misplaced neurons (gray matter), most often situated along the ventricular walls or within the subcortical white matter.
Glioblastoma multiforme
MedGen UID:
301585
Concept ID:
C1621958
Neoplastic Process
A tumor arising from glia in the central nervous system with macroscopic regions of necrosis and hemorrhage. Microscopically, glioblastoma multiforme is characterized by regions of pseudopalisading necrosis, pleomorphic nuclei and cells, and microvascular proliferation.
Cafe au lait spots, multiple
MedGen UID:
396266
Concept ID:
C1861975
Disease or Syndrome
The presence of six or more cafe-au-lait spots.

Professional guidelines

PubMed

Karpel HC, Slomovitz B, Coleman RL, Pothuri B
Curr Opin Obstet Gynecol 2023 Jun 1;35(3):270-278. Epub 2023 Mar 20 doi: 10.1097/GCO.0000000000000855. PMID: 36943683
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
Wimmer K, Kratz CP, Vasen HF, Caron O, Colas C, Entz-Werle N, Gerdes AM, Goldberg Y, Ilencikova D, Muleris M, Duval A, Lavoine N, Ruiz-Ponte C, Slavc I, Burkhardt B, Brugieres L; EU-Consortium Care for CMMRD (C4CMMRD)
J Med Genet 2014 Jun;51(6):355-65. Epub 2014 Apr 15 doi: 10.1136/jmedgenet-2014-102284. PMID: 24737826

Recent clinical studies

Etiology

Karpel HC, Slomovitz B, Coleman RL, Pothuri B
Curr Opin Obstet Gynecol 2023 Jun 1;35(3):270-278. Epub 2023 Mar 20 doi: 10.1097/GCO.0000000000000855. PMID: 36943683
Karpel H, Slomovitz B, Coleman RL, Pothuri B
Int J Gynecol Cancer 2023 Mar 6;33(3):343-350. doi: 10.1136/ijgc-2022-003676. PMID: 36878569
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
André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators
N Engl J Med 2020 Dec 3;383(23):2207-2218. doi: 10.1056/NEJMoa2017699. PMID: 33264544
Dinarvand P, Davaro EP, Doan JV, Ising ME, Evans NR, Phillips NJ, Lai J, Guzman MA
Arch Pathol Lab Med 2019 Nov;143(11):1382-1398. Epub 2019 May 9 doi: 10.5858/arpa.2018-0570-RA. PMID: 31070935

Diagnosis

Riedinger CJ, Esnakula A, Haight PJ, Suarez AA, Chen W, Gillespie J, Villacres A, Chassen A, Cohn DE, Goodfellow PJ, Cosgrove CM
Cancer 2024 Feb 1;130(3):385-399. Epub 2023 Sep 26 doi: 10.1002/cncr.35030. PMID: 37751191Free PMC Article
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
Olave MC, Graham RP
Genes Chromosomes Cancer 2022 Jun;61(6):314-321. Epub 2021 Dec 9 doi: 10.1002/gcc.23015. PMID: 34837268
Dinarvand P, Davaro EP, Doan JV, Ising ME, Evans NR, Phillips NJ, Lai J, Guzman MA
Arch Pathol Lab Med 2019 Nov;143(11):1382-1398. Epub 2019 May 9 doi: 10.5858/arpa.2018-0570-RA. PMID: 31070935
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr
Science 2017 Jul 28;357(6349):409-413. Epub 2017 Jun 8 doi: 10.1126/science.aan6733. PMID: 28596308Free PMC Article

Therapy

Karpel HC, Slomovitz B, Coleman RL, Pothuri B
Curr Opin Obstet Gynecol 2023 Jun 1;35(3):270-278. Epub 2023 Mar 20 doi: 10.1097/GCO.0000000000000855. PMID: 36943683
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
André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators
N Engl J Med 2020 Dec 3;383(23):2207-2218. doi: 10.1056/NEJMoa2017699. PMID: 33264544
Lichtenstern CR, Ngu RK, Shalapour S, Karin M
Cells 2020 Mar 4;9(3) doi: 10.3390/cells9030618. PMID: 32143413Free PMC Article
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr
Science 2017 Jul 28;357(6349):409-413. Epub 2017 Jun 8 doi: 10.1126/science.aan6733. PMID: 28596308Free PMC Article

Prognosis

Karpel HC, Slomovitz B, Coleman RL, Pothuri B
Curr Opin Obstet Gynecol 2023 Jun 1;35(3):270-278. Epub 2023 Mar 20 doi: 10.1097/GCO.0000000000000855. PMID: 36943683
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
Olave MC, Graham RP
Genes Chromosomes Cancer 2022 Jun;61(6):314-321. Epub 2021 Dec 9 doi: 10.1002/gcc.23015. PMID: 34837268
Dinarvand P, Davaro EP, Doan JV, Ising ME, Evans NR, Phillips NJ, Lai J, Guzman MA
Arch Pathol Lab Med 2019 Nov;143(11):1382-1398. Epub 2019 May 9 doi: 10.5858/arpa.2018-0570-RA. PMID: 31070935
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr
Science 2017 Jul 28;357(6349):409-413. Epub 2017 Jun 8 doi: 10.1126/science.aan6733. PMID: 28596308Free PMC Article

Clinical prediction guides

de Vries NL, van de Haar J, Veninga V, Chalabi M, Ijsselsteijn ME, van der Ploeg M, van den Bulk J, Ruano D, van den Berg JG, Haanen JB, Zeverijn LJ, Geurts BS, de Wit GF, Battaglia TW, Gelderblom H, Verheul HMW, Schumacher TN, Wessels LFA, Koning F, de Miranda NFCC, Voest EE
Nature 2023 Jan;613(7945):743-750. Epub 2023 Jan 11 doi: 10.1038/s41586-022-05593-1. PMID: 36631610Free PMC Article
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
Olave MC, Graham RP
Genes Chromosomes Cancer 2022 Jun;61(6):314-321. Epub 2021 Dec 9 doi: 10.1002/gcc.23015. PMID: 34837268
André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators
N Engl J Med 2020 Dec 3;383(23):2207-2218. doi: 10.1056/NEJMoa2017699. PMID: 33264544
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr
Science 2017 Jul 28;357(6349):409-413. Epub 2017 Jun 8 doi: 10.1126/science.aan6733. PMID: 28596308Free PMC Article

Recent systematic reviews

Mitric C, Salman L, Abrahamyan L, Kim SR, Pechlivanoglou P, Chan KKW, Gien LT, Ferguson SE
Gynecol Oncol 2023 Mar;170:133-142. Epub 2023 Jan 20 doi: 10.1016/j.ygyno.2022.12.008. PMID: 36682091
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
Atwal A, Snowsill T, Dandy MC, Krum T, Newton C, Evans DG, Crosbie EJ, Ryan NAJ
Int J Cancer 2022 Nov 1;151(9):1626-1639. Epub 2022 Jul 6 doi: 10.1002/ijc.34165. PMID: 35792468Free PMC Article
Travaglino A, Raffone A, Santoro A, Raimondo D, Orsini B, Casadio P, Zullo F, Seracchioli R, Zannoni GF, Insabato L, Mollo A
Pathobiology 2022;89(4):198-204. Epub 2022 Mar 1 doi: 10.1159/000521876. PMID: 35231921
Baxter NN, Kennedy EB, Bergsland E, Berlin J, George TJ, Gill S, Gold PJ, Hantel A, Jones L, Lieu C, Mahmoud N, Morris AM, Ruiz-Garcia E, You YN, Meyerhardt JA
J Clin Oncol 2022 Mar 10;40(8):892-910. Epub 2021 Dec 22 doi: 10.1200/JCO.21.02538. PMID: 34936379

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