CHD2基因突变导致Dravet综合征1例病例报告

邓小鹿 何 芳 吴丽文 尹 飞 彭 镜

·病案报告·

CHD2基因突变导致Dravet综合征1例病例报告

邓小鹿1,2何 芳1,2吴丽文1,2尹 飞1,2彭 镜1,2

1 病例资料

患儿G2P2，足月顺产，出生史无异常，发作前精神运动发育正常，1岁3个月独走，2岁讲简短句子。母亲幼时有“抽搐”史，姐姐幼时有“高热惊厥史”。

体格检查：神志清楚，反应迟滞，多动，不听指令，语言吐词不清，营养中等，面容及头颅无畸形，无眼球震颤，听力正常。内科查体未见异常。四肢肌力、肌张力未见异常，腱反射未见异常，病理征未引出。

图1 患儿脑电图表现

注 多量广泛性尖波、棘波、2.5～4 Hz棘慢波发放

图2 患儿及其家庭成员CHD2基因测序结果

注 A：患儿基因测序可见chr15:93552398-93552398存在 c.4438dupA 的杂合突变(红色箭头)，导致氨基酸改变p.V1479fs(缬氨酸>移码突变)；B：患儿父亲chr15:93552398-93552398无突变；C：患儿母亲chr15:93552398-93552398无突变

出院后随访发作控制3个月(期间无发热)，5岁1个月因扁桃体炎高热再次出现抽搐，意识丧失，眉毛频繁抖动，左手抽动，持续约20 min缓解，将托吡酯加量至3.75 mg·kg-1·d-1后暂无发作。

2 讨论

[1]Sun H, Zhang Y, Liu X, et al. Analysis of SCN1A mutation and parental origin in patients with Dravet Syndrome. J Hum Genet, 2010, 55(7): 421-427

[2]Scheffer IE. Diagnosis and long-term course of Dravet syndrome. Eur J Paediatr Neruol, 2012, 16 Suppl:S5-8

[3]Suls A, Jaehn JA, Kecskés A, et al. De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome. Am J Hm Genet, 2013, 93(5): 967-975

[4]Carvill GL, Heavin SB, Yendle SC, et al. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 . Nat Genet, 2013, 45(7): 825-830

[5]Thomas RH, Zhang LM, Carvill GL, et al. CHD2〗 myoclonic encephalopathy is frequently associated with self-induced seizures. Neurology, 2015, 84(9): 951-958

[6]Chénier S, Yoon G, Argiropoulos B, et al. CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems. J Neurodev Disord, 2014, 6(1): 9

[7]Lund C, Brodtkorb E, ∅ye AM, et al. CHD2 mutations in Lennox-Gastaut syndrome. Epilepsy Behav, 2014, 33: 18-21

[8]Galizia EC, Myers CT, Leu C, et al. CHD2 variants are a risk factor for photosensitivity in epilepsy. Brain, 2015, 138(Pt 5): 1198-1207

[9]O'Roak BJ, Stessman HA, Boyle EA, et al. Recurrent de novo mutations implicate novel genes underlying simplex autism risk. Nat Commun, 2014, 5: 5595

(本文编辑：张崇凡，孙晋枫)

国家自然科学基金项目：81370771，81371434；湖南省自然科学基金项目： 2015JJ3151

1中南大学湘雅医院儿科 长沙，410008；2湖南省儿童智力障碍研究中心 长沙，410008

彭镜，E-mail：pengjing4346@163.com

10.3969/j.issn.1673-5501.2016.06.015

2016-11-17

2016-12-07)