Huntsman Cancer Institute Department of Pathology Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112-5550, USA.
Clin Genet. 2011 Oct;80(4):394-7. doi: 10.1111/j.1399-0004.2010.01543.x. Epub 2010 Oct 6.
Constitutional mismatch repair-deficiency (CMMR-D) syndrome is an autosomal recessive condition characterized by hematologic malignancies, brain tumors, Lynch syndrome-associated cancers and skin manifestations reminiscent of neurofibromatosis type 1 (NF1). In contrast to Lynch syndrome, CMMR-D syndrome is exceptionally rare, onset typically occurs in infancy or early childhood and, as described in this report, may also present with colonic polyposis suggestive of attenuated familial adenomatous polyposis (AFAP) or MUTYH associated polyposis (MAP). Here we describe two sisters with CMMR-D syndrome due to germline bi-allelic MSH6 mutations. Both sisters are without cancer, are older than typical for this condition, have NF1 associated features and a colonic phenotype suspicious for an attenuated polyposis syndrome. This report highlights the role of skin examinations in leading to an underlying genetic diagnosis in individuals with colonic adenomatous polyposis, but without mutations associated with AFAP or MAP.
错配修复缺陷（CMMR-D）综合征是一种常染色体隐性疾病，其特征为血液系统恶性肿瘤、脑肿瘤、林奇综合征相关癌症和类似于 1 型神经纤维瘤病（NF1）的皮肤表现。与林奇综合征不同，CMMR-D 综合征极为罕见，发病通常发生在婴儿期或幼儿期，如本报告所述，也可能表现出结肠息肉，提示存在减弱的家族性腺瘤性息肉病（AFAP）或 MUTYH 相关息肉病（MAP）。在这里，我们描述了两名由于种系双等位基因突变导致 CMMR-D 综合征的姐妹。这两名姐妹均无癌症，年龄大于该疾病的典型发病年龄，具有 NF1 相关特征和结肠表型，提示存在减弱的息肉病综合征。本报告强调了皮肤检查在导致具有结肠腺瘤性息肉但无与 AFAP 或 MAP 相关突变的个体进行潜在遗传诊断中的作用。
