TY - JOUR T1 - Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort JF - Journal of Medical Genetics JO - J Med Genet SP - 770 LP - 778 DO - 10.1136/jmedgenet-2015-103299 VL - 52 IS - 11 AU - N Lavoine AU - C Colas AU - M Muleris AU - S Bodo AU - A Duval AU - N Entz-Werle AU - F Coulet AU - O Cabaret AU - F Andreiuolo AU - C Charpy AU - G Sebille AU - Q Wang AU - S Lejeune AU - M P Buisine AU - D Leroux AU - G Couillault AU - G Leverger AU - J P Fricker AU - R Guimbaud AU - M Mathieu-Dramard AU - G Jedraszak AU - O Cohen-Hagenauer AU - L Guerrini-Rousseau AU - F Bourdeaut AU - J Grill AU - O Caron AU - S Baert-Dusermont AU - J Tinat AU - G Bougeard AU - T Frébourg AU - L Brugières Y1 - 2015/11/01 UR - http://jmg.bmj.com/content/52/11/770.abstract N2 - 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. ER -