Article Text

Download PDFPDF
Original research
High yield of surveillance in patients diagnosed with constitutional mismatch repair deficiency
  1. Zeinab Ghorbanoghli1,
  2. Mariëtte van Kouwen2,
  3. Birgitta Versluys3,
  4. Delphine Bonnet4,
  5. Christine Devalck5,
  6. Julie Tinat6,
  7. Danuta Januszkiewicz-Lewandowska7,
  8. Consuelo Calvino Costas8,
  9. Edouard Cottereau9,
  10. James C H Hardwick1,
  11. Katharina Wimmer10,
  12. Laurence Brugieres11,
  13. Chrystelle Colas12,13,
  14. Hans F A Vasen1
  1. 1 Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Department of Gastroenterology and Hepatology, Radboud University, Nijmegen, The Netherlands
  3. 3 Department of pediatric stem cell transplantation, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
  4. 4 Department of Internale and Digestive Diseases, Pole Digestif, Paul Sabatier University, Toulouse, France
  5. 5 Department of Hemato-Oncology, Université Libre de Bruxelles, Bruxelles, Belgium
  6. 6 CHU Bordeaux, Nom du Service hospitalier, F-33000 Bordeaux, France
  7. 7 Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland
  8. 8 Servicio de Pediatría, Hospital Universitario Lucus Augusti, Lugo, Spain
  9. 9 Service de Génétique Médicale, CHRU Tours, Tours, France
  10. 10 Department of Genetics, Institute of Human Genetics, Medical University Innsbruck, Innsbruck, Austria
  11. 11 Department of Children and Adolescents Oncology, Gustave Roussy Institute, Villejuif, France
  12. 12 Department of Genetics, Institut Curie, PSL Research University, Paris, France
  13. 13 Inserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe Labellisée Par la Ligue Nationale Contre le Cancer, Paris, France
  1. Correspondence to Dr Zeinab Ghorbanoghli, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands; z.ghorbanoghli{at}


Background Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessively inherited syndrome that is caused by biallelic pathogenic variants of the mismatch repair genes. It is characterised by the development of multiple tumours in the first and second decade of life including brain, gastrointestinal and haematological tumours often resulting in early death. In order to improve the prognosis of these patients, the European collaborative group ‘care for CMMRD’ developed a surveillance programme in 2014 and established a registry of patients with CMMRD in Paris. The aim of the study was to evaluate the outcome of this programme.

Methods Twenty-two patients with a definitive diagnosis of CMMRD and with at least one follow-up study were selected from the registry. Medical data on the outcome of surveillance were collected from these patients.

Results During a mean follow-up of 4 years, the programme detected eight malignant tumours including three brain tumours, three upper gastrointestinal cancers and two colorectal cancers. Most tumours could successfully be treated. In addition, many adenomas were detected in the duodenum, and colorectum and subsequently removed. Seven patients developed a symptomatic malignancy, including two brain tumours, one small bowel cancer and four haematological malignancies. At the end of the follow-up, 16 out of 22 patients (73%) who participated in the surveillance programme were still alive.

Conclusion The study suggests a beneficial effect of surveillance of the digestive tract and brains.

  • genetic predisposition to disease
  • germ-line mutation

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

View Full Text


  • Contributors Conception and design: HFAV. Provision of study materials or patients: all authors. Collection and assembly of data: ZG, HFAV. Data analysis and interpretation: ZG, HFAV. Manuscript writing: ZG, HFAV. Guarantors: ZG, HFAV. Final approval of manuscript: all authors.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.