鄧小鹿 何 芳 吳麗文 尹 飛 彭 鏡

·病案報告·

CHD2基因突變導致Dravet綜合征1例病例報告

鄧小鹿1,2何 芳1,2吳麗文1,2尹 飛1,2彭 鏡1,2

1 病例資料

患兒G2P2，足月順產，出生史無異常，發(fā)作前精神運動發(fā)育正常，1歲3個月獨走，2歲講簡短句子。母親幼時有“抽搐”史，姐姐幼時有“高熱驚厥史”。

體格檢查：神志清楚，反應遲滯，多動，不聽指令，語言吐詞不清，營養(yǎng)中等，面容及頭顱無畸形，無眼球震顫，聽力正常。內科查體未見異常。四肢肌力、肌張力未見異常，腱反射未見異常，病理征未引出。

圖1 患兒腦電圖表現

注 多量廣泛性尖波、棘波、2.5～4 Hz棘慢波發(fā)放

圖2 患兒及其家庭成員CHD2基因測序結果

注 A：患兒基因測序可見chr15:93552398-93552398存在 c.4438dupA 的雜合突變(紅色箭頭)，導致氨基酸改變p.V1479fs(纈氨酸>移碼突變)；B：患兒父親chr15:93552398-93552398無突變；C：患兒母親chr15:93552398-93552398無突變

出院后隨訪發(fā)作控制3個月(期間無發(fā)熱)，5歲1個月因扁桃體炎高熱再次出現抽搐，意識喪失，眉毛頻繁抖動，左手抽動，持續(xù)約20 min緩解，將托吡酯加量至3.75 mg·kg-1·d-1后暫無發(fā)作。

2 討論

[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

(本文編輯：張崇凡，孫晉楓)

國家自然科學基金項目：81370771，81371434；湖南省自然科學基金項目： 2015JJ3151

1中南大學湘雅醫(yī)院兒科 長沙，410008；2湖南省兒童智力障礙研究中心 長沙，410008

彭鏡，E-mail：pengjing4346@163.com

10.3969/j.issn.1673-5501.2016.06.015

2016-11-17

2016-12-07)