Abstract:
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.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Lavoine N,Colas C,Muleris M,Bodo S,Duval A,Entz-Werle N,Coulet F,Cabaret O,Andreiuolo F,Charpy C,Sebille G,Wang Q,Lejeune S,Buisine MP,Leroux D,Couillault G,Leverger G,Fricker JP,Guimbaud R,Mathieu-Dramard M,Jedradoi
10.1136/jmedgenet-2015-103299subject
Has Abstractpub_date
2015-11-01 00:00:00pages
770-8issue
11eissn
0022-2593issn
1468-6244pii
jmedgenet-2015-103299journal_volume
52pub_type
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