P16: Constitutive mismatch repair deficiency syndrome: clinical description in a French cohort

Noémie Lavoine1, Chrystelle Colas2, Gwendoline Sebille3, Odile Cabaret4, Cécile Charpy5, Thierry Frébourg6, Natacha Entz-Werle7, Qing Wang8, Sophie Lejeune9, Dominique Leroux10, Gérard Couillault11, Guy Leverger12, Jean Pierre Fricker13, Rosine Guimbaud14, Michelle Mathieu-Dramard15, Franck Bourdeaut16, Martine Muleris17, Olivier Caron18, Laurence Brugières1.

1 – Département de cancérologie de l’enfant et de l’adolescent, Institut Gustave Roussy, Villejuif, France. 2 – Laboratoire d’oncogénétique et d’angiogénétique, Département de génétique, GH Pitié-Salpêtrière, APHP, Paris, France. 3 – Département de dermatologie, Institut Gustave Roussy, Villejuif, France. 4 – Département de biologie et pathologie médicales, Service de génétique, Institut Gustave Roussy, Villejuif, France. 5 – Département d’anatomo-pathologie, Institut Gustave Roussy, Villejuif, France. 6 – Laboratoire de génétique, Hôpital universitaire, Institut pour la recherche biomédicale et l’innovation, Rouen, France. 7 – Département d’oncologie pédiatrique, Centre hospitalier universitaire, Strasbourg, France. 8 – Plateforme mixte de génétique constitutionnelle des cancers fréquents HCL-CLB, Centre Léon Bérard, Lyon, France. 9 – Département de génétique clinique, Hôpital Jeanne de Flandre, Lille, France. 10 – Département de génétique, Hôpital universitaire, Grenoble, France. 11 – Département de pédiatrie, Hôpital universitaire, Dijon, France. 12 – Département d’hématologie et d’oncologie pédiatriques, Hôpital d’enfants Armand Trousseau, Paris, France. 13 – Département d’oncogénétique, Centre Paul Strauss, Strasbourg, France. 14 – Département d’oncologie digestive, Institut Claudius Régaud et hôpital universitaire de Toulouse, Toulouse, France. 15 – Unité de génétique médicale, hôpital universitaire d’Amiens, Amiens, France. 16 – Département d’oncologie pédiatrique, Institut Curie, Paris, France. 17 – Centre de Recherche Saint-Antoine INSERM / UMR S938, Equipe ”Instabilité des microsatellites et cancer” Paris, France. 18 – Département d’oncogénétique, Institut Gustave Roussy, Villejuif, France


Constitutive mismatch repair deficiency syndrome (CMMRD) is a childhood cancer predisposition syndrome involving biallelic mutations of MMR genes.


We performed a retrospective review of 31 cases of CMMRD from 23 families diagnosed in French genetics laboratories in order to describe clinical and genetics characteristics, treatment and outcome of malignancies.


67 tumours were diagnosed: 17 hematologic malignancies, 22 brain tumours, 25 Lynch syndrome-associated malignancies, and 3 other tumours. Median age of onset of first tumour was 6.98 years [1.23-33.53]. 23 patients had NF1-unrelated CALMs or hypopigmented macules and 4 had brain malformative features. Adenomas were found in all 16 patients who have had colonoscopy.

18 patients died, 7 due to the primary tumour. Median survival after diagnosis of the primary tumour was 23 months [0.26-213.2]. Among the patients who survived, 20 developed a second malignancy. A familial history of LS was found in only 6 families, and consanguinity in 43% of cases. PMS2 mutations (18 patients) were more frequent than mutations of MLH1 (4), MSH2 (3) and MSH6 (6).


CMMRD is a severe condition with multiple malignancies in childhood. Its rarity warrants international collaboration to define diagnosis criteria and guidelines for surveillance and prevention in order to decrease tumour-related mortality.