Williams-Beuren综合征的临床及遗传学特点:2例报道

doi:10.3969/j.issn.1671-167X.2017.05.028

摘要/Abstract

摘要： 通过分析2例WBS患儿临床表现,个人史,心脏超声、头颅磁共振成像、脑电图及染色体检测结果的特点,探讨Williams-Beuren综合征(Williams-Beuren syndrome,WBS)的临床及遗传学特点,以提高对该疾病的认识。2例患儿均为男性,就诊年龄分别为11个月1天和9个月9天,均存在心血管畸形,病例1为主动脉瓣上狭窄,病例2为房间隔缺损、动脉导管未闭。患儿具有WBS特征性面容:眶周饱满、球形鼻头、鼻梁低平、长人中、厚嘴唇。精神发育迟滞:病例1为中-重度,病例2为重度。其他表现:病例1合并双侧腹股沟斜疝和鞘膜积液,病例2合并喂养困难、埋藏式阴茎及婴儿痉挛。个人史:病例1孕期曾保胎,后因羊水污染足月剖宫产娩出。辅助检查:2例患儿头颅磁共振成像均未见明显异常,病例2脑电图示高度失律并监测到痉挛发作。染色体检测结果:病例1通过多重连接依赖的探针扩增法确定为染色体7q11.23缺失,其内包含人弹性蛋白(elastin,ELN)基因片段缺失突变;病例2通过高分辨G带法确定为染色体7q11.21q11.23缺失。本组2例WBS患儿均存在心血管畸形、特殊面容、精神发育迟滞及结缔组织或泌尿系统异常,病例1的主动脉瓣上狭窄可能与ELN基因缺失相关,病例2的癫痫发生可能与超出7q11.23区域的q11.21缺失相关。

关键词: Williams-Beuren综合征, 染色体缺失, 婴儿痉挛, 基因

Abstract: SUMMARY To explore the clinical and genetic characteristics of Williams-Beuren syndrome (WBS) and to raise awareness of the disease. The characteristics of clinical manifestations, personal history, cardiac ultrasound, brain magnetic resonance imaging (MRI), electroencephalogram (EEG) and chromosome detection results of two cases with WBS were analyzed. The two patients were both male and the age was 11 months and 1 day, and 9 months and 9 days, respectively. They both suffered from cardiovascular malformation: case one presented supravalvular aortic stenosis, and case two showed atrial septal defect and patent ductus arteriosus. Both of the cases were exhibited characteristic facial features of WBS, including full orbital, spherical nose, flat nasal bridge, long philtrum and thick lips. For the mental deve-lopment, case one displayed moderate to severe developmental retardation, and case two showed severe developmental retardation. In addition, case one presented bilateral indirect inguinal hernia and hydrocele, and case two manifested feeding difficulties, buried penis and infantile spasms. Personal history: case one’s mother had tocolytic therapy during pregnancy period, and case one was born at full-term by cesarean section due to amniotic fluid pollution. Supplementary examination: brain MRI of the two cases were no significant abnormalities, the EEG of case two showed hypsarrhythmia, and the epileptic spasms were recorded. Chromosome detection results: case one was identified as 7q11.23 deletion including the fragment deletion mutation of elastin (ELN) gene by multiplex ligation dependent probe amplification method, and case two was found with 7q11.21q11.23 deletion by high resolution G-band method. The two cases with WBS both had cardiovascular malformations, special facial features, mental retardation and connective tissue or urinary system abnormality. The supravalvular aortic stenosis of case one may be associated with the deletion of ELN gene, and the occurrence of epilepsy of case two may be related to the q11.21 deletion beyond the 7q11.23 region.

Key words: Williams-Beuren syndrome, Chromosomes deletion, Infantile spasms, Genes

中图分类号:

R596.1

王姝琪, 杨志仙, 李慧. Williams-Beuren综合征的临床及遗传学特点:2例报道[J]. 北京大学学报(医学版), 2017, 49(5): 899-903.

WANG Shu-qi, YANG Zhi-xian, LI Hui. Clinical and genetic characteristics of Williams-Beuren syndrome: 2 cases report[J]. Journal of Peking University(Health Sciences), 2017, 49(5): 899-903.

参考文献

[1] Williams JCP, Barratt-Boyes BG, Lowe JB. Supravalvular aortic stenosis [J]. Circulation, 1961, 24(6): 1311-1318.
[2] Beuren AJ, Apitz J, Koncz J. Die diagnose und Beurteilung der verschiedenen formen der supravalvulären aortenstenose [J]. Zeitschrift Kreislaufforsch, 1962, 51: 829-837.
[3] Stromme P, Bjornstad PG, Ramstad K. Prevalence estimation of Williams syndrome [J]. J Child Neurol, 2002, 17(4): 269-271.
[4] Amenta S, Sofocleous C, Kolialexi A, et al. Clinical manifestations and molecular investigation of 50 patients with Williams syndrome in the Greek population [J]. Pediatr Res, 2005, 57(6): 789-795.
[5] Li L, Huang L, Luo Y, et al. Differing microdeletion sizes and breakpoints in chromosome 7q11.23 in Williams-Beuren syndrome detected by chromosomal microarray analysis [J]. Mol Syndromol, 2016, 6(6): 268-275.
[6] Ewart AK, Morris CA, Atkinson D, et al. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome [J]. Nat Genet, 1993, 5(1): 11-16.
[7] Curran ME, Atkinson DL, Ewart AK, et al. The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis [J]. Cell, 1993, 73(1): 159-168.
[8] Li DY, Toland AE, Boak BB, et al. Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis [J]. Hum Mol Genet, 1997, 6(7): 1021-1028.
[9] Tassabehji M, Metcalfe K, Donnai D, et al. Elastin: genomic structure and point mutations in patients with supravalvular aortic stenosis [J]. Hum Mol Genet, 1997, 6(7): 1029-1036.
[10] Sugayama SM, Moises RL, Wagenfur J, et al. Williams-Beuren syndrome: cardiovascular abnormalities in 20 patients diagnosed with fluorescence in situ hybridization [J]. Arq Bras Cardiol, 2003, 81(5): 462-473.
[11] Committee on Genetics. American Academy of Pediatrics: Health care supervision for children with Williams syndromes [J]. Pe-diatrics, 2001, 107(5): 1192-1204.
[12] 吕俊健, 周伟, 陈珊. 以反复心律失常为主要表现的新生儿Williams-Beuren综合征1例[J]. 中华实用儿科临床杂志, 2015, 30(20): 1593-1594.
[13] Karmiloff-Smith A, Grant J, Ewing S, et al. Using case study comparisons to explore genotype-phenotype correlations in Williams-Beuren syndrome [J]. J Med Genet, 2003, 40(2): 136-140.
[14] 解春红, 杨建滨, 邵洁, 等. 威廉斯综合征25例的荧光原位杂交检测[J]. 中华医学遗传学杂志, 2007, 24(1): 104-106.
[15] 解春红, 赵正言. 威廉斯综合征的基因型和认知表型研究[J]. 国际儿科学杂志, 2006, 33(2): 117-119.
[16] Nicita F, Garone G, Spalice A, et al. Epilepsy is a possible feature in Williams-Beuren syndrome patients harboring typical deletions of the 7q11.23 critical region [J]. Am J Med Genet A, 2016, 170A(1): 148-155.
[17] Scherer SW, Osborne L. Williams-Beuren syndrome [M]// Lupski J, Stankiewicz P. Genomic disorders: the genomic basis of disease. Totowa NJ: Human Press, 2006: 221-236.
[18] Tassabehji M. Williams-Beuren syndrome: a challenge for genotype phenotype-correlations [J]. Hum Mol Genet, 2003, 12(2): R229-237.
[19] Fusco C, Micale L, Augello B, et al. Smaller and larger deletions of the Williams Beuren syndrome region implicate genes involved in mild facial phenotype, epilepsy and autistic traits [J]. Eur J Hum Genet, 2014, 22(1): 64-70.
[20] Dai L, Bellugi U, Chen XN, et al. Is it Williams syndrome? GTF2IRD1 implicated in visual-spatial construction and GTF2I in sociability revealed by high resolution arrays [J]. Am J Med Genet A, 2009, 149A(3): 302-314.
[21] Samanta D. Infantile spasms in Williams-Beuren syndrome with typical deletions of the 7q11.23 critical region and a review of the literature [J]. Acta Neurol Belg, 2016, 117(1): 359-362.
[22] Ramocki MB, Bartnik M, Szafranski P, et al. Recurrent distal 7q11.23 deletion including HIPI and YWHAG identified in patients with intellectual disabilities, epilepsy, and neurobehavioral problems [J]. Am J Hum Genet, 2010, 87(6): 857-865.
[23] Mizugishi K, Yamanaka K, Kuwajima K. Interstitial deletion of chromosome 7q in a patient with Williams syndrome and infantile spasms [J]. J Hum Genet, 1998, 43(3): 178-181.
[24] Marshall CR, Young EJ, Pani AM, et al. Infantile spasms is associated with deletion of the MAGI2 gene on chromosome 7q11.23-q21.22 [J]. Am J Hum Genet, 2008, 83(1): 106-111.

相关文章 15

[1]	殷昊明, 王子杰, 舒帆, 张展奕, 梁会, 张树栋. 肾透明细胞癌FABP6基因长转录本的表达及意义[J]. 北京大学学报（医学版）, 2026, 58(2): 393-398.
[2]	耿芸玲, 刘超, 杨萍, 郑佳佳, 沈宁, 杜毅鹏. 医院获得性肺炎患者肺炎克雷伯菌多部位感染的临床特征及毒力基因分布[J]. 北京大学学报（医学版）, 2026, 58(1): 201-207.
[3]	刘艳华, 陆敏, 赵旭阳, 张宽根, 武睿, 梅放, 戴志豪, 由江峰, 裴斐. 肿瘤转移抑制基因LASS2去磷酸化对液泡型ATP酶活性及前列腺癌侵袭性的影响[J]. 北京大学学报（医学版）, 2025, 57(6): 1113-1123.
[4]	董琪, 何菁, 贾园, 姚海红, 张霞. 模拟复发性多软骨炎的VEXAS综合征1例[J]. 北京大学学报（医学版）, 2025, 57(6): 1180-1183.
[5]	张展奕, 陆敏, 孙悦皓, 董靖晗, 侯小飞, 肖春雷, 王国良, 田晓军, 马潞林, 张洪宪, 张树栋. TFE3重排肾细胞癌合并静脉癌栓患者的临床病理特征及生存分析[J]. 北京大学学报（医学版）, 2025, 57(4): 650-661.
[6]	李梦迪, 雷蕾, 刘中宁, 李健, 姜婷. siRNA沉默NLK基因促进神经化组织工程骨再生[J]. 北京大学学报（医学版）, 2025, 57(2): 227-236.
[7]	张真伟, 徐欣然, 高学军, 董艳梅, 田华. RELT基因移码突变导致遗传性釉质发育不全[J]. 北京大学学报（医学版）, 2025, 57(1): 13-18.
[8]	马民英, 晁晓芹, 赵扬, 赵国廷. LncRNA SNHG20靶向调控miR-520c-3p/RAB22A通路对人口腔鳞状细胞癌细胞上皮间质转化及微管形成的影响[J]. 北京大学学报（医学版）, 2025, 57(1): 26-32.
[9]	帅婷, 郭艳艳, 林春平, 侯晓玫, 金婵媛. 敲减NPTX1促进人骨髓间充质干细胞成骨分化[J]. 北京大学学报（医学版）, 2025, 57(1): 7-12.
[10]	金银姬, 刘蕊. 以肠系膜静脉血栓为突出表现的遗传性蛋白S缺乏症1例[J]. 北京大学学报（医学版）, 2024, 56(6): 1106-1109.
[11]	李炳乐, 朱凌妍, 王永福, 白力. 褪黑素调控节律基因表达及其缓解间质性肺纤维化的机制[J]. 北京大学学报（医学版）, 2024, 56(6): 963-971.
[12]	焦莶如, 龚潘, 牛悦, 徐兆, 周宗朴, 杨志仙. 以婴儿癫痫性痉挛综合征为表型的吡哆醇依赖性癫痫[J]. 北京大学学报（医学版）, 2024, 56(5): 781-787.
[13]	武志慧, 胡明智, 赵巧英, 吕凤凤, 张晶莹, 张伟, 王永福, 孙晓林, 王慧. miR-125b-5p修饰脐带间充质干细胞对系统性红斑狼疮的免疫调控机制[J]. 北京大学学报（医学版）, 2024, 56(5): 860-867.
[14]	郭煌达,彭和香,王斯悦,侯天姣,李奕昕,章涵宇,王梦莹,武轶群,秦雪英,唐迅,李劲,陈大方,胡永华,吴涛. 短期大气颗粒物暴露和MTNR1B基因多态性对甘油三酯-葡萄糖指数影响的家系研究[J]. 北京大学学报（医学版）, 2024, 56(3): 375-383.
[15]	侯天姣,周治波,王竹青,王梦莹,王斯悦,彭和香,郭煌达,李奕昕,章涵宇,秦雪英,武轶群,郑鸿尘,李静,吴涛,朱洪平. 转化生长因子β信号通路与非综合征型唇腭裂发病风险的基因-基因及基因-环境交互作用[J]. 北京大学学报（医学版）, 2024, 56(3): 384-389.

Metrics

Viewed

Full text

Abstract

Cited

Shared

Discussed