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Constitutional mismatch repair deficiency syndrome

MedGen UID:
1378836
•Concept ID:
C4321324
•
Disease or Syndrome
Synonyms: Biallelic Mismatch Repair Deficiency Syndrome; CMMR-D (constitutional mismatch repair deficiency) syndrome; Constitutional Mis-Match Repair Deficiency Syndrome; Constitutional Mismatch Repair Deficiency Syndrome; Constitutional MMR Deficiency
SNOMED CT: CMMR-D (constitutional mismatch repair deficiency) syndrome (764946008); Constitutional mismatch repair deficiency syndrome (764946008)

Definition

A rare inherited cancer-predisposing syndrome characterised by the development of a broad spectrum of malignancies during childhood, including mainly brain, haematological and gastrointestinal cancers, although embryonic and other tumours have also been occasionally reported. Non-neoplastic features, in particular manifestations reminiscent of neurofibromatosis type 1 (for example cafe au lait spots, freckling, neurofibromas), as well as premalignant and non-malignant lesions (such as adenomas/polyps) are frequently present before malignancy development. [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVConstitutional mismatch repair deficiency syndrome

Professional guidelines

PubMed

Diagnostic criteria for constitutional mismatch repair deficiency (CMMRD): recommendations from the international consensus working group.
Aronson M, Colas C, Shuen A, Hampel H, Foulkes WD, Baris Feldman H, Goldberg Y, Muleris M, Wolfe Schneider K, McGee RB, Jasperson K, Rangaswami A, Brugieres L, Tabori U
J Med Genet 2022 Apr;59(4):318-327. Epub 2021 Feb 23 doi: 10.1136/jmedgenet-2020-107627. PMID: 33622763
Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood.
Tabori U, Hansford JR, Achatz MI, Kratz CP, Plon SE, Frebourg T, Brugières L
Clin Cancer Res 2017 Jun 1;23(11):e32-e37. doi: 10.1158/1078-0432.CCR-17-0574. PMID: 28572265
Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium 'care for CMMRD' (C4CMMRD).
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

Diagnostic criteria for constitutional mismatch repair deficiency (CMMRD): recommendations from the international consensus working group.
Aronson M, Colas C, Shuen A, Hampel H, Foulkes WD, Baris Feldman H, Goldberg Y, Muleris M, Wolfe Schneider K, McGee RB, Jasperson K, Rangaswami A, Brugieres L, Tabori U
J Med Genet 2022 Apr;59(4):318-327. Epub 2021 Feb 23 doi: 10.1136/jmedgenet-2020-107627. PMID: 33622763
Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance.
Durno C, Ercan AB, Bianchi V, Edwards M, Aronson M, Galati M, Atenafu EG, Abebe-Campino G, Al-Battashi A, Alharbi M, Azad VF, Baris HN, Basel D, Bedgood R, Bendel A, Ben-Shachar S, Blumenthal DT, Blundell M, Bornhorst M, Bronsema A, Cairney E, Rhode S, Caspi S, Chamdin A, Chiaravalli S, Constantini S, Crooks B, Das A, Dvir R, Farah R, Foulkes WD, Frenkel Z, Gallinger B, Gardner S, Gass D, Ghalibafian M, Gilpin C, Goldberg Y, Goudie C, Hamid SA, Hampel H, Hansford JR, Harlos C, Hijiya N, Hsu S, Kamihara J, Kebudi R, Knipstein J, Koschmann C, Kratz C, Larouche V, Lassaletta A, Lindhorst S, Ling SC, Link MP, Loret De Mola R, Luiten R, Lurye M, Maciaszek JL, MagimairajanIssai V, Maher OM, Massimino M, McGee RB, Mushtaq N, Mason G, Newmark M, Nicholas G, Nichols KE, Nicolaides T, Opocher E, Osborn M, Oshrine B, Pearlman R, Pettee D, Rapp J, Rashid M, Reddy A, Reichman L, Remke M, Robbins G, Roy S, Sabel M, Samuel D, Scheers I, Schneider KW, Sen S, Stearns D, Sumerauer D, Swallow C, Taylor L, Thomas G, Toledano H, Tomboc P, Van Damme A, Winer I, Yalon M, Yen LY, Zapotocky M, Zelcer S, Ziegler DS, Zimmermann S, Hawkins C, Malkin D, Bouffet E, Villani A, Tabori U
J Clin Oncol 2021 Sep 1;39(25):2779-2790. Epub 2021 May 4 doi: 10.1200/JCO.20.02636. PMID: 33945292Free PMC Article
Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood.
Tabori U, Hansford JR, Achatz MI, Kratz CP, Plon SE, Frebourg T, Brugières L
Clin Cancer Res 2017 Jun 1;23(11):e32-e37. doi: 10.1158/1078-0432.CCR-17-0574. PMID: 28572265
Connections between constitutional mismatch repair deficiency syndrome and neurofibromatosis type 1.
Wimmer K, Rosenbaum T, Messiaen L
Clin Genet 2017 Apr;91(4):507-519. Epub 2017 Jan 10 doi: 10.1111/cge.12904. PMID: 27779754
The diagnostic and clinical significance of café-au-lait macules.
Shah KN
Pediatr Clin North Am 2010 Oct;57(5):1131-53. doi: 10.1016/j.pcl.2010.07.002. PMID: 20888463

Diagnosis

Diagnostic criteria for constitutional mismatch repair deficiency (CMMRD): recommendations from the international consensus working group.
Aronson M, Colas C, Shuen A, Hampel H, Foulkes WD, Baris Feldman H, Goldberg Y, Muleris M, Wolfe Schneider K, McGee RB, Jasperson K, Rangaswami A, Brugieres L, Tabori U
J Med Genet 2022 Apr;59(4):318-327. Epub 2021 Feb 23 doi: 10.1136/jmedgenet-2020-107627. PMID: 33622763
Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance.
Durno C, Ercan AB, Bianchi V, Edwards M, Aronson M, Galati M, Atenafu EG, Abebe-Campino G, Al-Battashi A, Alharbi M, Azad VF, Baris HN, Basel D, Bedgood R, Bendel A, Ben-Shachar S, Blumenthal DT, Blundell M, Bornhorst M, Bronsema A, Cairney E, Rhode S, Caspi S, Chamdin A, Chiaravalli S, Constantini S, Crooks B, Das A, Dvir R, Farah R, Foulkes WD, Frenkel Z, Gallinger B, Gardner S, Gass D, Ghalibafian M, Gilpin C, Goldberg Y, Goudie C, Hamid SA, Hampel H, Hansford JR, Harlos C, Hijiya N, Hsu S, Kamihara J, Kebudi R, Knipstein J, Koschmann C, Kratz C, Larouche V, Lassaletta A, Lindhorst S, Ling SC, Link MP, Loret De Mola R, Luiten R, Lurye M, Maciaszek JL, MagimairajanIssai V, Maher OM, Massimino M, McGee RB, Mushtaq N, Mason G, Newmark M, Nicholas G, Nichols KE, Nicolaides T, Opocher E, Osborn M, Oshrine B, Pearlman R, Pettee D, Rapp J, Rashid M, Reddy A, Reichman L, Remke M, Robbins G, Roy S, Sabel M, Samuel D, Scheers I, Schneider KW, Sen S, Stearns D, Sumerauer D, Swallow C, Taylor L, Thomas G, Toledano H, Tomboc P, Van Damme A, Winer I, Yalon M, Yen LY, Zapotocky M, Zelcer S, Ziegler DS, Zimmermann S, Hawkins C, Malkin D, Bouffet E, Villani A, Tabori U
J Clin Oncol 2021 Sep 1;39(25):2779-2790. Epub 2021 May 4 doi: 10.1200/JCO.20.02636. PMID: 33945292Free PMC Article
Connections between constitutional mismatch repair deficiency syndrome and neurofibromatosis type 1.
Wimmer K, Rosenbaum T, Messiaen L
Clin Genet 2017 Apr;91(4):507-519. Epub 2017 Jan 10 doi: 10.1111/cge.12904. PMID: 27779754
Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium 'care for CMMRD' (C4CMMRD).
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
The diagnostic and clinical significance of café-au-lait macules.
Shah KN
Pediatr Clin North Am 2010 Oct;57(5):1131-53. doi: 10.1016/j.pcl.2010.07.002. PMID: 20888463

Therapy

Lynch syndrome-associated ultra-hypermutated pediatric glioblastoma mimicking a constitutional mismatch repair deficiency syndrome.
Yang C, Austin F, Richard H, Idowu M, Williamson V, Sabato F, Ferreira-Gonzalez A, Turner SA
Cold Spring Harb Mol Case Stud 2019 Oct;5(5) Epub 2019 Oct 23 doi: 10.1101/mcs.a003863. PMID: 31604779Free PMC Article
B-cell acute lymphoblastic leukemia with high mutation burden presenting in a child with constitutional mismatch repair deficiency.
Oshrine B, Grana N, Moore C, Nguyen J, Crenshaw M, Edwards M, Sudhaman S, Forster VJ, Tabori U
Blood Adv 2019 Jun 25;3(12):1795-1798. doi: 10.1182/bloodadvances.2019000358. PMID: 31189528Free PMC Article
Current clinical topics of Lynch syndrome.
Tanakaya K
Int J Clin Oncol 2019 Sep;24(9):1013-1019. Epub 2018 May 9 doi: 10.1007/s10147-018-1282-7. PMID: 29744602
Immunotherapy holds the key to cancer treatment and prevention in constitutional mismatch repair deficiency (CMMRD) syndrome.
Westdorp H, Kolders S, Hoogerbrugge N, de Vries IJM, Jongmans MCJ, Schreibelt G
Cancer Lett 2017 Sep 10;403:159-164. Epub 2017 Jun 20 doi: 10.1016/j.canlet.2017.06.018. PMID: 28645564
Diagnosis of Constitutional Mismatch Repair-Deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents.
Bodo S, Colas C, Buhard O, Collura A, Tinat J, Lavoine N, Guilloux A, Chalastanis A, Lafitte P, Coulet F, Buisine MP, Ilencikova D, Ruiz-Ponte C, Kinzel M, Grandjouan S, Brems H, Lejeune S, Blanché H, Wang Q, Caron O, Cabaret O, Svrcek M, Vidaud D, Parfait B, Verloes A, Knappe UJ, Soubrier F, Mortemousque I, Leis A, Auclair-Perrossier J, Frébourg T, Fléjou JF, Entz-Werle N, Leclerc J, Malka D, Cohen-Haguenauer O, Goldberg Y, Gerdes AM, Fedhila F, Mathieu-Dramard M, Hamelin R, Wafaa B, Gauthier-Villars M, Bourdeaut F, Sheridan E, Vasen H, Brugières L, Wimmer K, Muleris M, Duval A; European Consortium “Care for CMMRD”
Gastroenterology 2015 Oct;149(4):1017-29.e3. Epub 2015 Jun 25 doi: 10.1053/j.gastro.2015.06.013. PMID: 26116798

Prognosis

Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance.
Durno C, Ercan AB, Bianchi V, Edwards M, Aronson M, Galati M, Atenafu EG, Abebe-Campino G, Al-Battashi A, Alharbi M, Azad VF, Baris HN, Basel D, Bedgood R, Bendel A, Ben-Shachar S, Blumenthal DT, Blundell M, Bornhorst M, Bronsema A, Cairney E, Rhode S, Caspi S, Chamdin A, Chiaravalli S, Constantini S, Crooks B, Das A, Dvir R, Farah R, Foulkes WD, Frenkel Z, Gallinger B, Gardner S, Gass D, Ghalibafian M, Gilpin C, Goldberg Y, Goudie C, Hamid SA, Hampel H, Hansford JR, Harlos C, Hijiya N, Hsu S, Kamihara J, Kebudi R, Knipstein J, Koschmann C, Kratz C, Larouche V, Lassaletta A, Lindhorst S, Ling SC, Link MP, Loret De Mola R, Luiten R, Lurye M, Maciaszek JL, MagimairajanIssai V, Maher OM, Massimino M, McGee RB, Mushtaq N, Mason G, Newmark M, Nicholas G, Nichols KE, Nicolaides T, Opocher E, Osborn M, Oshrine B, Pearlman R, Pettee D, Rapp J, Rashid M, Reddy A, Reichman L, Remke M, Robbins G, Roy S, Sabel M, Samuel D, Scheers I, Schneider KW, Sen S, Stearns D, Sumerauer D, Swallow C, Taylor L, Thomas G, Toledano H, Tomboc P, Van Damme A, Winer I, Yalon M, Yen LY, Zapotocky M, Zelcer S, Ziegler DS, Zimmermann S, Hawkins C, Malkin D, Bouffet E, Villani A, Tabori U
J Clin Oncol 2021 Sep 1;39(25):2779-2790. Epub 2021 May 4 doi: 10.1200/JCO.20.02636. PMID: 33945292Free PMC Article
Position paper: Challenges and specific strategies for constitutional mismatch repair deficiency syndrome in low-resource settings.
Kebudi R, Amayiri N, Abedalthagafi M, Rana AN, Kirmani S, Musthaq N, Lamki ZA, Houdzi JE, Yazici H, El-Naggar S, Edwards M, Bianchi VJ, Durno C, Tabori U, Bouffet E; International RRD Consortium on Low-Resource Settings Panel
Pediatr Blood Cancer 2020 Aug;67(8):e28309. Epub 2020 May 30 doi: 10.1002/pbc.28309. PMID: 32472748
Current clinical topics of Lynch syndrome.
Tanakaya K
Int J Clin Oncol 2019 Sep;24(9):1013-1019. Epub 2018 May 9 doi: 10.1007/s10147-018-1282-7. PMID: 29744602
Acute lymphoblastic leukemia and lymphoma in the context of constitutional mismatch repair deficiency syndrome.
Ripperger T, Schlegelberger B
Eur J Med Genet 2016 Mar;59(3):133-42. Epub 2015 Dec 30 doi: 10.1016/j.ejmg.2015.12.014. PMID: 26743104
Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer.
Carethers JM, Stoffel EM
World J Gastroenterol 2015 Aug 21;21(31):9253-61. doi: 10.3748/wjg.v21.i31.9253. PMID: 26309352Free PMC Article

Clinical prediction guides

Position paper: Challenges and specific strategies for constitutional mismatch repair deficiency syndrome in low-resource settings.
Kebudi R, Amayiri N, Abedalthagafi M, Rana AN, Kirmani S, Musthaq N, Lamki ZA, Houdzi JE, Yazici H, El-Naggar S, Edwards M, Bianchi VJ, Durno C, Tabori U, Bouffet E; International RRD Consortium on Low-Resource Settings Panel
Pediatr Blood Cancer 2020 Aug;67(8):e28309. Epub 2020 May 30 doi: 10.1002/pbc.28309. PMID: 32472748
Current clinical topics of Lynch syndrome.
Tanakaya K
Int J Clin Oncol 2019 Sep;24(9):1013-1019. Epub 2018 May 9 doi: 10.1007/s10147-018-1282-7. PMID: 29744602
Acute lymphoblastic leukemia and lymphoma in the context of constitutional mismatch repair deficiency syndrome.
Ripperger T, Schlegelberger B
Eur J Med Genet 2016 Mar;59(3):133-42. Epub 2015 Dec 30 doi: 10.1016/j.ejmg.2015.12.014. PMID: 26743104
Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer.
Carethers JM, Stoffel EM
World J Gastroenterol 2015 Aug 21;21(31):9253-61. doi: 10.3748/wjg.v21.i31.9253. PMID: 26309352Free PMC Article
Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium 'care for CMMRD' (C4CMMRD).
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

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