N23: Digestive Burden Of CMMRD (Constitutional Mismatch Repair Deficiency) Patients And Overlap With Lynch Syndrome: Report From The European Care4CMMRD Consortium

M. Le Mentec1, H. Delhomelle2, J. Viala3, E. Cottereau4, D. Bonnet5, T. Frébourg6, L. Faivre7, S. Lejeune8, N. Entz-Werle9, J. Tinat10, F. Desseigne11, D. Leroux12, A. Verschuur13, N. Janin14, C. Devalck15, S. Unger16, A. Bemoussa17, E. Kabickova18, M. Genuardi19, D. Rueda20, Z. Levi21, Y. Goldberg22, C. Ruiz-Ponte23, M. Muleris24, K. Wimmer25, H. Vasen26, L. Brugières27, C. Colas28

1 – Curie Institute, Paris, France. 2 – CHU Saint Antoine (APHP), Sorbonne University, Paris, France. 3 – Hôpital Robert Debré, Paris, France. 4 – CHRU, Tours, France. 5 – CHU Purpan, Toulouse, France. 6 – CHU, Rouen, France. 7 – CHU, Dijon, France. 8 – CHU, Lille, France. 9 – CHU, Strasbourg, France. 10 – CHU, Bordeaux, France. 11 – Centre Léon Berard, Lyon, France. 12 – CHU, Grenoble, France. 13 – Hôpital de la Timone, Marseille, France. 14 – Cliniques Universitaires Saint-Luc, Brussels, Belgium. 15 – HUDERF, Belgium. 16 – Centre hospitalier universitaire vaudois, Lausanne, Switzerland. 17 – Faculté de Medecine et de Pharmacie, Casablanca, Morocco. 18 – University Hospital, Prague, Czech Republic. 19 – Policlinico Universitario A. Gemelli, Roma, Italia. 20 – Hospital 12 de Octubre, Madrid, Spain. 21 – Beilinson Medical Center, Petah Tikva, Israel. 22 – Sharett Institute, Hadassah Hebrew University Medical Center, Jerusalem, Israel. 23 – Fundacion Pública Galega, Santiago Compostela, Spain. 24 – INSERM U938, Paris, France. 25 – Medizinische Universität Innsbruck, Innsbruck, Austria. 26 – Leiden University Medical Centre, Leiden, Netherlands. 27 – Gustave Roussy, Villejuif, France. 28 – Curie Institute, Paris, France On behalf of the C4CMMRD consortium.


Aim: Constitutional Mismatch Repair Deficiency (CMMRD), due to biallelic germline mutations in one MMR gene, is characterized by multiple and very early-onset malignancies including Lynch-related tumors. We describe the digestive burden of these patients with their phenotypical presentation, somatic datas and phenotype-genotype correlations.

Method: Digestive phenotype was reported in 45/78 patients registered in the C4MMRD database.

Results: Overall, 37 digestives cancers (DC) were observed in 27 patients (35 colorectal, 1 stomach,1 duodenal, 1 small bowel cancer). Median age at first DC was 17,5 (7-33). DC was the first tumor for 14 patients. Thirteen patients are alive at last follow-up, 7 patients died because of their DC and 7 of other cancers.

32 patients (including 23 with DC) had multiple colic adenomas at a median age of 16 (9-33).

Conclusion: CMMRD patients have severe digestive burden with early-onset multiple adenomas and cancers in upper and lower digestive tract. An early and intensive screening of those lesions is required as some of them could be removed to prevent cancer.

Some data also support the existence of a clinical overlap between CMMRD and Lynch Syndrome. This is suggestive of a genetic continuum whose mechanism is still unknown. We discuss several hypotheses and propose collaborations.