Boyle M I, Jespersgaard C, Brøndum-Nielsen K, Bisgaard A-M, Tümer Z
Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Glostrup, Denmark.
Clin Genet. 2015 Jul;88(1):1-12. doi: 10.1111/cge.12499. Epub 2014 Oct 28.
Cornelia de Lange syndrome (CdLS; MIM #122470, 300590, 610759, 614701, 300882) is a rare and clinically variable disorder that affects multiple organs. It is characterized by intellectual disability (mild to severe), distinctive facial features, prenatal and postnatal growth retardation, and hirsutism. Congenital anomalies include malformations of the upper limbs, gastrointestinal malformation/rotation, pyloric stenosis, diaphragmatic hernia, heart defects and genitourinary malformations. Gastroesophageal reflux disease is present in almost all patients. In addition to classic forms, milder phenotypes have been reported. To date five genes [NIPBL (Nipped-B-like protein), SMC1A (structural maintenance of chromosomes 1A), SMC3 (structural maintenance of chromosomes 3), RAD21 (human homolog of Schizosaccharomyces pombe radiation sensitive mutant 21) and HDAC8 (histone deacetylase 8)] have been associated with CdLS and mutations of these genes comprise the underlying defect in 70% of the patients. Here, we will provide a brief review of the clinical features of CdLS, summarize the known underlying genetic defects, prenatal and postnatal diagnosis possibilities, and genetic counseling.
科妮莉亚·德朗热综合征（CdLS；医学遗传学在线数据库编号#122470、300590、610759、614701、300882）是一种罕见的、临床特征多变的疾病，会影响多个器官。其特征包括智力残疾（轻度至重度）、独特的面部特征、产前和产后生长发育迟缓以及多毛症。先天性异常包括上肢畸形、胃肠道畸形/旋转、幽门狭窄、膈疝、心脏缺陷和泌尿生殖系统畸形。几乎所有患者都存在胃食管反流病。除了典型形式外，还报告了症状较轻的表型。迄今为止，已有五个基因[NIPBL（类Nipped-B蛋白）、SMC1A（染色体结构维持蛋白1A）、SMC3（染色体结构维持蛋白3）、RAD21（粟酒裂殖酵母辐射敏感突变体21的人类同源物）和HDAC8（组蛋白去乙酰化酶8）]与CdLS相关，这些基因的突变构成了70%患者的潜在缺陷。在此，我们将简要综述CdLS的临床特征，总结已知的潜在遗传缺陷、产前和产后诊断方法以及遗传咨询。
