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Guidelines for surveillance of individuals with constitutional mismatch repair-deficiency proposed by the European Consortium “Care for CMMR-D” (C4CMMR-D)
  1. H F A Vasen1,2,
  2. Z Ghorbanoghli2,
  3. F Bourdeaut3,
  4. O Cabaret4,
  5. O Caron5,
  6. A Duval6,
  7. N Entz-Werle7,
  8. Y Goldberg8,
  9. D Ilencikova9,
  10. C P Kratz10,
  11. N Lavoine11,
  12. J Loeffen12,
  13. F H Menko13,
  14. M Muleris6,
  15. G Sebille14,
  16. C Colas15,6,
  17. B Burkhardt16,
  18. L Brugieres11,
  19. K Wimmer17,
  20. on behalf of the EU-Consortium Care for CMMR-D (C4CMMR-D)
  1. 1Department of Gastroenterology & Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
  2. 2Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, The Netherlands
  3. 3Department of Pediatric Oncology, Institute Curie, Paris, France
  4. 4Department of Genetics, Gustave Roussy Cancer Institute, Villejuif, France
  5. 5Department of Oncogenetics, Gustave Roussy Cancer Institute, Villejuif, France
  6. 6Inserm, Team ‘Microsatellite Instability and Cancer’, UMRS 938, Saint-Antoine Hospital, Paris, France
  7. 7Department of Pediatric Oncology, University Hospital, Strasbourg, France
  8. 8Department of Oncology, Sharret Institute, Hadassah Hebrew Medical Centre, Jerusalem, Israel
  9. 9Department of Pediatrics, Comenius University Medical School, University Children's Hospital, Bratislava, Slovakia
  10. 10Department of Pediatric Hematology & Oncology, Hannover Medical School, Hannover, Germany
  11. 11Department of Pediatrics, Gustave Roussy Cancer Institute, Villejuif, France
  12. 12Department of Pediatric Hematology & Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands
  13. 13Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
  14. 14Department of Dermatology, Gustave Roussy Cancer Institute, Villejuif, France
  15. 15Department of Genetics, Pitie Salpetriere Hospital, APHP, Paris, France
  16. 16Department of Pediatric Hematology & Oncology, University Hospital Munster, Munster, Germany
  17. 17Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria
  1. Correspondence to Professor Dr HFA Vasen, Department of Gastroenterology & Hepatology, Leiden University Medical Centre, Rijnsburgerweg 10, Leiden 2333 AA, The Netherlands; hfavasen{at}


Lynch syndrome (LS) is an autosomal dominant disorder caused by a defect in one of the DNA mismatch repair genes: MLH1, MSH2, MSH6 and PMS2. In the last 15 years, an increasing number of patients have been described with biallelic mismatch repair gene mutations causing a syndrome referred to as ‘constitutional mismatch repair-deficiency’ (CMMR-D). The spectrum of cancers observed in this syndrome differs from that found in LS, as about half develop brain tumours, around half develop digestive tract cancers and a third develop haematological malignancies. Brain tumours and haematological malignancies are mainly diagnosed in the first decade of life, and colorectal cancer (CRC) and small bowel cancer in the second and third decades of life. Surveillance for CRC in patients with LS is very effective. Therefore, an important question is whether surveillance for the most common CMMR-D-associated cancers will also be effective. Recently, a new European consortium was established with the aim of improving care for patients with CMMR-D. At a workshop of this group held in Paris in June 2013, one of the issues addressed was the development of surveillance guidelines. In 1968, criteria were proposed by WHO that should be met prior to the implementation of screening programmes. These criteria were used to assess surveillance in CMMR-D. The evaluation showed that surveillance for CRC is the only part of the programme that largely complies with the WHO criteria. The values of all other suggested screening protocols are unknown. In particular, it is questionable whether surveillance for haematological malignancies improves the already favourable outcome for patients with these tumours. Based on the available knowledge and the discussions at the workshop, the European consortium proposed a surveillance protocol. Prospective collection of all results of the surveillance is needed to evaluate the effectiveness of the programme.

  • CMMR-D
  • Constitutional mismatch repair deficiency
  • Surveillance
  • Guidelines
  • Tumour spectrum
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