Min Ko Jung, Cho Jae So, Yoo Yongjin, Seo Jieun, Choi Murim, Chae Jong-Hee, Lee Hye-Ran, Cho Tae-Joon
1 Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.
2 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
J Child Neurol. 2017 Feb;32(2):237-242. doi: 10.1177/0883073816674095. Epub 2016 Oct 24.
Wiedemann-Steiner syndrome is a rare genetic disorder characterized by short stature, hairy elbows, facial dysmorphism, and developmental delay. It can also be accompanied by musculoskeletal anomalies such as muscular hypotonia and small hands and feet. Mutations in the KMT2A gene have only recently been identified as the cause of Wiedemann-Steiner syndrome; therefore, only 16 patients from 15 families have been described, and new phenotypic features continue to be added. In this report, we describe 2 newly identified patients with Wiedemann-Steiner syndrome who presented with variable severity. One girl exhibited developmental dysplasia of the hip and fibromatosis colli accompanied by other clinical features, including facial dysmorphism, hypertrichosis, patent ductus arteriosus, growth retardation, and borderline intellectual disability. The other patient, a boy, showed severe developmental retardation with automatic self-mutilation, facial dysmorphism, and hypertrichosis at a later age. Exome sequencing analysis of these patients and their parents revealed a de novo nonsense mutation, p.Gln1978*, of KMT2A in the former, and a missense mutation, p.Gly1168Asp, in the latter, which molecularly confirmed the diagnosis of Wiedemann-Steiner syndrome.
维德曼-施泰纳综合征是一种罕见的遗传性疾病,其特征为身材矮小、肘部多毛、面部畸形和发育迟缓。它还可能伴有肌肉骨骼异常,如肌张力减退和手足过小。KMT2A基因的突变直到最近才被确定为维德曼-施泰纳综合征的病因;因此,仅描述了来自15个家庭的16例患者,并且新的表型特征仍在不断增加。在本报告中,我们描述了2例新确诊的维德曼-施泰纳综合征患者,其严重程度各不相同。一名女孩表现为髋关节发育不良和先天性肌性斜颈,并伴有其他临床特征,包括面部畸形、多毛症、动脉导管未闭、生长发育迟缓以及边缘智力障碍。另一名患者是男孩,在稍大年龄时表现出严重的发育迟缓,并伴有自残行为、面部畸形和多毛症。对这些患者及其父母进行外显子组测序分析发现,前者KMT2A基因存在一个新发无义突变p.Gln1978*,后者存在一个错义突变p.Gly1168Asp,从分子水平证实了维德曼-施泰纳综合征的诊断。