Cornelia de Lange综合征患者临床特征及其遗传学分析2例报告及文献复习  

Clinical characteristics and genetic analysis of patients with Cornelia de Lange syndrome:A report of 2 cases and literature review

作　　者：蔡美娇 陈佳燕 马小敏 黄燕茹 张剑 葛运生[1,2] CAI Meijiao;CHEN Jiayan;MA Xiaomin;HUANG Yanru;ZHANG Jian;GE Yunsheng(Department of Central Laboratory,Xiamen Maternal and Child Health Hospital,Xiamen 361003,China;Department of Central Laboratory,Women and Children’s Hospital,Xiamen University,Xiamen 361003,China;Department of Medical Imaging,Women and Children’s Hospital,Xiamen University,Xiamen 361003,China;School of Public Health,Xiamen University,Xiamen 361002,China)

机构地区：[1]福建省厦门市妇幼保健院中心实验室,福建厦门361003 [2]厦门大学附属妇女儿童医院中心实验室,福建厦门361003 [3]厦门大学附属妇女儿童医院放射科,福建厦门361003 [4]厦门大学公共卫生学院,福建厦门361002

出　　处：《吉林大学学报(医学版)》2025年第2期501-507,共7页Journal of Jilin University:Medicine Edition

基　　金：国家自然科学基金青年基金项目(82101955);福建省科技厅自然科学基金创新青年项目(2023J05269);福建省卫健委卫生健康科技计划项目(2020GGB064);福建省厦门市科技局医疗卫生指导性项目(3502Z20224ZD1228)。

摘　　要：Cornelia de Lange综合征(CdLS)是一种罕见的先天性畸形疾病,其典型特征包括生长受限、智力迟钝、颅面异常和多毛症等。本研究报道2例CdLS患者,对其临床表现和基因变异特点进行总结,并结合相关文献进行复习。患者1,女性,5岁,因生长发育缓慢就诊。查体多毛,一字眉,牙齿小、稀疏,前胸、后背可见血管瘤(约2 cm×2 cm),语言发育迟缓,智力落后;身高98 cm [≤-2标准差(SD)],体质量15 kg (-2SD~-1SD),头围46 cm (-3SD~-2SD);脑核磁共振成像(MRI)平扫显示左侧侧脑室侧后角和双侧侧脑室三角略扩大,双侧上颌窦和筛窦黏膜轻度增厚,心脏彩超显示二、三尖瓣轻度反流。患者2,女性,1个月,生后气促,软腭裂,吞咽困难及三凹征阳性,双手小、左手通贯掌、右手第5指短小,右侧髋关节外展受限,双足内翻,右眼底白斑。1个月时超声显示三尖瓣轻度反流,房间隔卵圆孔未闭。2d时脑MRI平扫显示纵裂池及天幕可见少许斑片状低信号影,少量蛛网膜下腔出血,双侧上颌窦、筛窦和中耳乳突少量积液。染色体核型分析未见明显结构及数目异常。全外显子组测序检测,患者1存在NIPBL基因c.6653_6655del杂合变异,患者2存在NIPBL基因c.337C>T杂合变异,父母均未检测到该变异。NIPBL基因变异是CdLS患者的主要遗传学病因,基因变异c.337C>T的鉴定扩展了NIPBL基因的变异谱系,为研究CdLS患者致病性基因变异提供了新证据。Cornelia de Lange syndrome is a rare congenital malformation disease,and its typical features include growth restriction,mental retardation,craniofacial abnormality and hirsutism.This study reported 2 cases of CdLS patients,summarized their clinical manifestations and gene mutation characteristics,and the relevant literatures were reviewed.Patient 1,a 5-year-old girl,was admitted to the hospital due to growth retardation.Physical examination revealed hirsutism,monobrow,small and sparse teeth,hemangiomas(approximately 2 cm×2 cm)on the chest and back,delayed language development,and intellectual disability.The height was 98 cm[≤-2 standard deviation(SD)],the weight was 15 kg(-2SD--1SD),the head circumference was 46 cm(-3SD--2SD).Brain magnetic resonance imaging(MRI)plain scan showed slightly enlarged left lateral ventricle and bilateral lateral ventricle triangles,slightly thickened bilateral maxillary sinus and ethmoid sinus mucosa.Echocardiography revealed mild regurgitation of the mitral and tricuspid valves.Patient 2,a 1-month-old girl,was admitted to the hospital due to postpartum shortness of breath.The physical examination highlighted hirsutism,short nose,soft cleft palate,dysphagia,positive three-concave sign,audible throat sound,small hands,palm penetration in the left hand,short fifth finger of the right hand,limited right hip abduction,foot varus,and a white spot at the bottom of the right eye.Ultrasonography at 1 month showed mild regurgitation of the tricuspid valve and an open foramen ovale.Brain MRI at 2 d showed a few patchy low-signal shadows in the longitudinal fissure cistern and tentorium,a small amount of subarachnoid hemorrhage,and a small amount of fluid in the bilateral maxillary sinus,ethmoid sinus,and middle ear mastoid.No obvious structural or numerical abnormalities were observed in the chromosome karyotypes.Whole-exome sequencing detected a heterozygous variation of c.6653_6655del in the NIPBL gene in patient 1 and a heterozygous variation of c.337C>T in the NIPBL gene in patient 2.T

关 键 词：Cornelia de Lange综合征 NIPBL基因 基因变异 变异谱系 

分 类 号：R725.9[医药卫生—儿科]