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 M P, Leroux D, Couillault G, Leverger G, Fricker J P, Guimbaud R, Mathieu-Dramard M, Jedraszak G, Cohen-Hagenauer O, Guerrini-Rousseau L, Bourdeaut F, Grill J, Caron O, Baert-Dusermont S, Tinat J, Bougeard G, Frébourg T, Brugières L
Department of Children and Adolescents Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
Laboratory of Oncogenetics and Angiogenetics, Genetics Department, Pitié-Salpêtrière University Hospital, APHP, Paris, France INSERM, UMR_S 938, CDR Saint-Antoine, Paris, France Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, France.
J Med Genet. 2015 Nov;52(11):770-8. doi: 10.1136/jmedgenet-2015-103299. Epub 2015 Aug 28.
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.
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.
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)).
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.
先天性错配修复缺陷（CMMRD）综合征是一种儿童癌症易感性综合征，涉及错配修复（MMR）基因的双等位基因种系突变，迄今为止临床医生对此认识不足。
对法国遗传学实验室诊断的所有31例CMMRD患者进行回顾性研究，以描述恶性肿瘤的特征、治疗及转归以及生物学诊断数据。
31例患者共诊断出67个肿瘤，其中25个（37%）为林奇综合征相关恶性肿瘤，22个（33%）为脑肿瘤，17个（25%）为血液系统恶性肿瘤，3个（5%）为肉瘤。首个肿瘤的中位发病年龄为6.9岁（1.2 - 33.5岁）。总体而言，22例患者死亡，9例（41%）死于原发性肿瘤。原发性肿瘤诊断后的中位生存期为27个月（0.26 - 213.2个月）。失败率似乎高于预期，尤其是T细胞非霍奇金淋巴瘤（12例中有6例进展/复发）。23个家庭中有6个有林奇综合征家族史，9个有近亲结婚史。PMS2突变（n = 18）比其他突变（MSH6（n = 6）、MLH1（n = 4）和MSH2（n = 3））更常见。
总之，这组未经选择的患者系列证实了该综合征的极端严重性，高死亡率主要与多种儿童癌症相关，并强调了早期检测以调整治疗和监测的必要性。
