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Original article
Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort
  1. N Lavoine1,
  2. C Colas2,3,4,
  3. M Muleris3,4,
  4. S Bodo3,4,
  5. A Duval3,4,
  6. N Entz-Werle5,
  7. F Coulet2,
  8. O Cabaret6,
  9. F Andreiuolo7,
  10. C Charpy8,
  11. G Sebille9,
  12. Q Wang10,
  13. S Lejeune11,
  14. M P Buisine11,12,13,
  15. D Leroux14,
  16. G Couillault15,
  17. G Leverger16,
  18. J P Fricker17,
  19. R Guimbaud18,
  20. M Mathieu-Dramard19,
  21. G Jedraszak19,
  22. O Cohen-Hagenauer20,
  23. L Guerrini-Rousseau1,
  24. F Bourdeaut21,
  25. J Grill1,22,
  26. O Caron23,
  27. S Baert-Dusermont24,
  28. J Tinat24,
  29. G Bougeard24,
  30. T Frébourg24,
  31. L Brugières1
  1. 1Department of Children and Adolescents Oncology, Gustave Roussy Cancer Campus, Villejuif, France
  2. 2Laboratory of Oncogenetics and Angiogenetics, Genetics Department, Pitié-Salpêtrière University Hospital, APHP, Paris, France
  3. 3INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France
  4. 4Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France
  5. 5Department of Pediatric Oncology, Strasbourg University Hospital, Strasbourg, France
  6. 6Department of Biology and Medical Pathology, Unit of Genetics, Gustave Roussy Cancer Campus, Villejuif, France
  7. 7Department of Neuropathology, Sainte-Anne Hospital, APHP, Paris, France
  8. 8Department of Pathology, Gustave Roussy Cancer Institute, Villejuif, France
  9. 9Department of Dermatology, Gustave Roussy Cancer Institute, Villejuif, France
  10. 10Plateforme mixte de génétique constitutionnelle des cancers fréquents HCL-CLB, Centre Léon Bérard, Lyon, France
  11. 11Unit of Molecular Oncology and Genetics, Institute of Biochemistry and Molecular Biology, Lille University Hospital, Lille, France
  12. 12Inserm UMR837, Lille, France
  13. 13North of France University, Lille, France
  14. 14Department of Genetics, Grenoble University Hospital, Grenoble, France
  15. 15Département of Pediatrics, Dijon University Hospital, Dijon, France
  16. 16Paediatric Onco-Haematology Unit, APHP, Armand Trousseau Hospital, UPMC Univ Paris 06, France
  17. 17Department of Oncogenetics, Centre Paul Strauss, Strasbourg, France
  18. 18Department of Digestive Oncology, Claudius Régaud Institute and Toulouse University Hospital, Toulouse, France
  19. 19Unit of Medical Genetics, Amiens University Hospital, Amiens, France
  20. 20Department of Oncogenetics, Saint-Louis University Hospital, APHP, Paris, France
  21. 21Department of Pediatric Oncology, Curie Institute, Paris, France
  22. 22CNRS UMR 8203 “Vectorology & Anticancer Treatments,” Gustave Roussy & Paris-Sud University, Villejuif, France
  23. 23Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France
  24. 24Laboratory of Genetics, Rouen University Hospital, Rouen, France
  1. Correspondence to Dr Laurence Brugières, Department of Children and Adolescent Oncology, Gustave Roussy Cancer Campus, 114 rue Edouard Vaillant, Villejuif Cedex F-94805, France; Laurence.brugieres{at}


Background Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far.

Methods Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data.

Results 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9 years (1.2–33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27 months (0.26–213.2). Failure rate seemed to be higher than expected especially for T-cell non-Hodgkin's lymphoma (progression/relapse in 6/12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)).

Conclusions In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.

  • MMR
  • genetic predisposition
  • childhood cancer
  • multiple cancer

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