Wojcik Monica H, Carmichael Nikkola, Bieber Frederick R, Wiener Daniel C, Madan Rachna, Pober Barbara R, Raby Benjamin A
Division of Newborn Medicine, Division of Genetics and Genomics, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Am J Med Genet A. 2017 Aug;173(8):2235-2239. doi: 10.1002/ajmg.a.38289. Epub 2017 Jun 2.
Williams-Beuren syndrome (WBS) is a chromosomal microdeletion syndrome typically presenting with intellectual disability, a unique personality, a characteristic facial appearance, and cardiovascular disease. Several clinical features of WBS are thought to be due to haploinsufficiency of elastin (ELN), as the ELN locus is included within the WBS critical region at 7q11.23. Emphysema, a disease attributed to destruction of pulmonary elastic fibers, has been reported in patients without WBS who have pathogenic variants in ELN but only once (in one patient) in WBS. Here we report a second adult WBS patient with emphysema where the diagnosis of WBS was established subsequent to the discovery of severe bullous emphysema. Haploinsufficiency of ELN likely contributed to this pulmonary manifestation of WBS. This case emphasizes the contribution of rare genetic variation in cases of severe emphysema and provides further evidence that emphysema should be considered in patients with WBS who have respiratory symptoms, as it may be under-recognized in this patient population.
威廉姆斯-贝伦综合征（WBS）是一种染色体微缺失综合征，通常表现为智力残疾、独特的性格、典型的面部外观和心血管疾病。WBS的几种临床特征被认为是由于弹性蛋白（ELN）单倍剂量不足所致，因为ELN基因座位于7q11.23的WBS关键区域内。肺气肿是一种因肺弹性纤维破坏而引起的疾病，在没有WBS但ELN存在致病变异的患者中已有报道，但在WBS患者中仅报道过一例（一名患者）。在此，我们报告第二例患有肺气肿的成年WBS患者，该患者在发现严重大疱性肺气肿后确诊为WBS。ELN单倍剂量不足可能导致了WBS的这种肺部表现。该病例强调了罕见基因变异在严重肺气肿病例中的作用，并进一步证明，对于有呼吸道症状的WBS患者应考虑肺气肿，因为在这一患者群体中可能未得到充分认识。
