双胎共患Wolf-Hirschhorn综合征一家系  

Family report of Wolf-Hirschhorn syndrome in twins

作　　者：王丽君[1] 董燕[1] 赵世超 李梦春 贾天明[1] 崔甲昱 郭芪良 连若斐 Wang Lijun;Dong Yan;Zhao Shichao;Li Mengchun;Jia Tianming;Cui Jiayu;Guo Qiliang;Lian Ruofei(Department of Pediatric Neurology,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第三附属医院小儿神经内科,郑州450052

出　　处：《中华神经科杂志》2023年第7期763-769,共7页Chinese Journal of Neurology

摘　　要：目的分析Wolf-Hirschhorn综合征(WHS)的临床表现及基因特点,提高对此病的诊断及鉴别诊断能力。方法观察2021年12月就诊于郑州大学第三附属医院的4p16.3区段微缺失所致的WHS先证者的临床特点、辅助检查,对其进行家系全外显子测序(WES),并对治疗反应及预后进行评估。结果先证者女性,11月龄,8月龄开始出现抽搐,发作有热敏感及丛集性特点,其同卵双胎姐姐有类似病史。体格检查:营养不良,发育落后,面容特殊,前额突出、鼻梁宽、下颌小,心前区可闻及全期3/6级杂音,P2亢进,四肢肌张力低。家系WES及拷贝数变异(CNV)检测发现,先证者染色体4p16.3区段存在1.99 Mb杂合缺失,包含WHSC1(NSD2)、WHSC2(NEFLA)等基因,先证者和姐姐基因组拷贝数变异测序(CNV-Seq)结果显示4p16.3区段分别存在1.97、1.92 Mb杂合缺失,经定量聚合酶链反应家系分析,该CNV来源为新发,根据美国医学遗传学与基因组学学会制订的遗传变异分类标准与指南,判定为致病性变异。先证者口服丙戊酸钠,其姐姐先后口服丙戊酸钠、唑尼沙胺、左乙拉西坦治疗,同时二人均进行家庭康复训练。末次随访年龄为1岁8月龄,二人近3个月均未再抽搐,但发育仍明显落后。结论WHS患者可表现为生长发育迟缓、癫痫、希腊武士头盔样特殊面容,伴有先天性心脏病,存在4p16.3区段微缺失。Objective To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome(WHS)to improve the ability of diagnosis and differential diagnosis of the disease.Methods The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded,and whole exome sequencing(WES)of the family was performed.The prognosis was followed up.Results The female proband,11 months old,presented with convulsions at the age of 8 months,with the characteristics of heat sensitivity and cluster seizures,and her identical twin sister had a similar medical history.Physical examination found malnutrition,retarded development,special face,prominent forehead,wide nasal bridge,small jaw,precordial murmur and grade 3/6 murmur in the whole period,hyperactivity of P2,and low limb muscle tone.The whole exon and copy number variation(CNV)test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment,including WHSC1(NSD2),WHSC2(NEFLA)and other genes.Copy number variation sequencing(CNV-Seq)of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3,respectively.Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo,and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines.The proband took sodium valproate orally,and her sister took oral sodium valproate,zonisamide,and levetiracetam successively,and at the same time they received family rehabilitation training.The age at the last follow-up was 1 year and 8 months.Neither of them had convulsions again in the past 3 months,but the developmental delay was obvious.Conclusion WHS patients may present with growth retardation,epilepsy,Greek warrior helmet-like special face,and congenital heart disease,and may have microdeletions

关 键 词：Wolf-Hirschhorn综合征 癫痫 发育迟缓 先天性心脏病 

分 类 号：R725.9[医药卫生—儿科]