新生儿德朗热综合征6例临床特点及基因变异分析

Clinical features and gene mutation analysis of 6 newborns with Cornelia de Lange syndrome

目的探讨新生儿德朗热综合征(CdLS)的临床特点及基因表型,并为临床医生提供识别和诊断CdLS的依据。方法回顾性分析了广州市妇女儿童医疗中心2018年1月至2022年12月期间收治的6例新生儿CdLS患儿,通过电子病历系统收集患儿的人口学信息、发病年龄、确诊年龄、产前诊断信息、临床表现等资料。参照2018年德朗热综合征诊断及管理国际专家共识提供的临床诊断标准及基因诊断,对患儿进行评分。对患儿进行全外显子测序和父母Sanger测序验证基因变异。门诊及电话随诊评估患儿预后。结果在这6例患儿中,男1例,女5例,均在新生儿期确诊。4例患儿具有典型的外貌特征,包括连眉和(或)浓眉,短鼻、凹鼻嵴和(或)鼻孔前倾,长人中和(或)人中扁平,薄上唇和(或)嘴角下弯,小头畸形,多毛,1例合并猫叫综合征,1例以梗阻性黄疸为主要表现。另外2例临床表现不典型,通过基因分析确诊CdLS。其中4例完成了基因诊断,NIPBL基因突变2例,HDAC8基因突变2例。本研究中的6例患儿,有1例放弃治疗后,在医院内拔除气管导管后因呼吸衰竭死亡,有3例出院后死亡,1例失访,仅有1例出院后在我院门诊不规律随诊,生长发育迟缓,目前存活3岁3个月。结论新生儿CdLS典型的临床表现为特殊的外貌和多器官系统发育异常,可通过典型临床特征进行识别,并可通过基因分析确诊。临床医生应当了解Cdls的临床特点和基因表型,进行早期的诊断并处理。

Objective To explore the clinical features and genotypes of Cornelia de Lange Syndrome(CdLS)in neonates,and to provide a basis for clinical identification and diagnosis of CdLS.Methods A retrospective analysis was conducted on six newborn CdLS children admitted to the Guangzhou Women and Children's Medical Center from January 2018 to December 2022.The demographic information,age of onset and diagnosis,prenatal diagnosis information,clinical manifestations,and other data of the patients were collected through the electronic medical record system.The children were scored according to the clinical diagnostic criteria and genetic diagnosis provided by the 2018 International Expert Consensus on the Diagnosis and Management of Cornelia de Lange Syndrome.Whole-exome sequencing was performed on the children,and the gene mutations were verified by Sanger sequencing of the parents.The prognosis of the children were assessed through outpatient and telephone follow-up.At the same time,relevant literature reviews were conducted.Results Among these six children,one was male and five were female,all of whom were diagnosed in the neonatal period.Four patients had typical facial features,including arched eyebrows and(or)bushy eyebrows,short nose,concave nasal bridge and(or)forward-leaning nostrils,long philtrum and(or)flat philtrum,thin upper lip and(or)downturned corners of the mouth,microcephaly,and hirsutism.Additionally,one child had Cri du Chat syndrome,while another child presented with obstructive jaundice as the main manifestation.The clinical manifestations of the other two children were not typical,and CdLS was confirmed through genetic analysis.Among them,genetic diagnosis was completed for four patients,with two of NIPBL gene mutation and two of HDAC8 gene mutation.Among the 6 children,one died of respiratory failure after giving up treatment and removing the tracheal tube in the hospital,three died after discharge,one was lost to follow-up,and only one was discharged and followed up irregularly at our hospital's outpatient department.The child is currently 3 years and 3 months old and is experiencing growth retardation.Conclusion The typical clinical presentation of CdLS in newborns includes distinctive facial features and multiple organ system malformations,which can be identified through typical clinical characteristics and confirmed by genetic analysis.It is important for clinical practitioners to understand the clinical features and genetic phenotype of CdLS and to facilitate early diagnosis and management.