3例Mowat-Wilson综合征患儿的临床特点及遗传学分析

Mowat-Wilson综合征（MWS）是一种由E盒结合锌指蛋白2（ZEB2）基因突变导致的罕见常染色体显性遗传病，临床表现多样，主要表现为智力障碍/全面发育迟缓、面容特殊，并伴有多种先天畸形。该文报道3例经ZEB2基因分析确诊为MWS患儿的临床特点和基因突变结果。3例均有先天性巨结肠及面容异常，其中病例1于4月龄死于重型心衰和肺炎，因年龄小，家长未能发现其全面发育迟缓，另2例均有重度全面发育迟缓。3例患儿均为ZEB2基因新生杂合无义突变携带者，其中c.756C > A （p.Y252X）为未见报道的新发突变，该类突变可产生截短蛋白，具有明确致病性。MWS临床和遗传异质性大，若患儿面容与MWS高度符合，且存在智力障碍/全面发育迟缓，合并多种先天畸形，临床医生应警惕MWS，基因检测有助于确立诊断。

Clinical and genetic features of Mowat-Wilson syndrome: an analysis of 3 cases

Mowat-Wilson syndrome (MWS) is a rare autosomal dominant genetic disease caused by zinc finger E-box-binding homeobox 2 (ZEB2) gene mutation and has various clinical manifestations including intellectual disability/global developmental delay, unusual facies and multiple congenital malformations. This article reports the clinical features and gene mutations of three children diagnosed with MWS by ZEB2 gene analysis. All three children had Hirschsprung disease and unusual facies. One child died of severe heart failure and pneumonia at the age of 4 months. Global developmental delay was not discovered by her parents due to her young age. The other two children had severe global developmental delay. All three children carried a de novo heterozygous nonsense mutation in the ZEB2 gene, among which c.756C > A (p.Y252X) had not been reported before. Such mutations produced truncated proteins and were highly pathogenic. MWS is presented with strong clinical and genetic heterogeneity. Clinicians should consider the possibility of MWS when a child has unusual facies of MWS, intellectual disability/global developmental delay and multiple congenital malformations. Gene detection helps to make a confirmed diagnosis.