Ohtahara Syndrome Caused by a Novel c.581C>T Mutation in the KCNQ2 Gene：a Case Report and Literature Review

doi:10.12114/j.issn.1007-9572.2019.00.019

Abstract

Abstract: Ohtahara syndrome （OS） is a rare epileptic encephalopathy，which is also known as early infantile epileptic encephalopathy.It is characterized by neonatal onset，typically frequent and uncontrollable tonic clonic seizure，characteristic suppression-burst patterns on electroencephalography （EEG），and severe psychomotor retardation.In this paper，we summarized the clinical features and gene mutation characteristics of one case with ohtahara syndrome caused by a novel c.581C>T mutation in the KCNQ2 gene.And relevant literature was reviewed to improve the awareness of this rare disease.Identification of gene mutations will be beneficial to early diagnosis，intervention，prognosis evaluation and genetic counseling for ohtahara syndrome.

Key words: Brain diseases；Ohtahara syndrome；KCNQ2 gene；c.581C>, T；Novel mutation

摘要： 大田原综合征（OS）是一种罕见的癫痫性脑病，也称为早期婴儿癫痫性脑病。其特征为新生儿期起病，频繁及难以控制的强直痉挛发作的临床表现、典型暴发-抑制脑电图及精神运动发育落后。本文总结了1例KCNQ2基因c.581C>T新发突变致OS患儿的临床特征及基因突变的特点，并进行文献复习，以期提高对该罕见病的认识。OS相关基因突变的识别，可为OS早期诊断、干预、预后判断和遗传咨询提供依据。

关键词: 脑疾病；大田原综合征；KCNQ2基因；c.581C>, T；新发突变

LI Guangxu,YU Shufeng,LU Jun, et al. Ohtahara Syndrome Caused by a Novel c.581C>T Mutation in the KCNQ2 Gene：a Case Report and Literature Review[J]. Chinese General Practice, 2019, 22(21): 2641-2644. DOI: 10.12114/j.issn.1007-9572.2019.00.019.
厉广栩,喻树峰,逯军等. KCNQ2基因c.581C>T新发突变致大田原综合征一例报道并文献复习[J]. 中国全科医学, 2019, 22(21): 2641-2644. DOI: 10.12114/j.issn.1007-9572.2019.00.019.

References

［1］OHTAHARA S.Seizure disorders in infancy and childhood［J］．Brain Dev，1984，6（6）：509-519.
［2］OHTAHARA S，YAMATOGI Y.Epileptic encephalopathies in early infancy with suppression-burst［J］．J Clin Neurophysiol，2003，20（6）：398-407.
［3］GIORDANO L，SARTORI S，RUSSO S，et al.Familial Ohtahara syndrome due to a novel ARX gene mutation［J］．Am J Med Genet A，2010，152A（12）：3133-3137．DOI：10.1002/ajmg.a.33701.
［4］SAITSU H，KATO M，MIZUGUCHI T，et al．De novo mutations in the gene encoding STXBP1（MUNC18-1）cause early infantile epileptic encephalopathy［J］．Nat Genet，2008，40（6）：782-788．DOI：10.1038/ng.150.
［5］KATO M，YAMAGATA T，KUBOTA M，et al．Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation［J］．Epilepsia，2013，54（7）：1282-1287．DOI：10.1111/epi.12200.
［6］GUERRINI R，NOEBELS J.How can advances in epilepsy genetics lead to better treatments and cures?［J］．Adv Exp Med Biol，2014，813：309-317．DOI：10.1007/978-94-017-8914-1_25.
［7］白薇，王爽.KCNQ2突变所致大田原综合征2例报告及文献复习［J］．中国实用儿科杂志，2015，30（9）：705-709．DOI：10.7504/ek2015090614.
［8］杨雪，潘岗，李文辉，等．不明病因早发癫痫性痉挛患儿遗传学研究［J］．中华儿科杂志，2017，55（11）：813-817．DOI：10.3760/cma.j.issn.0578-1310.2017.11.004.
YANG X，PAN G，LI W H，et al．Analysis of gene mutation of early onset epileptic spasm with unknown reason［J］．Chin J Pediatr，2017，55（11）：813-817．DOI：10.3760/cma.j.issn.0578-1310.2017.11.004.
［9］ZHANG Q，LI J，ZHAO Y，et al．Gene mutation analysis of 175 Chinese patients with early onset epileptic encephalopathy［J］．Clin Genet，2017，91（5）：717-724．DOI：10.1111/cge.12901.
［10］MARTIN H C，KIM G E，PAGNAMENTA A T，et al．Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis［J］．Hum Mol Genet，2014，23（12）：3200-3211．DOI：10.1093/hmg/ddu030.
［11］MILH M，BOUTRY-KRYZA N，SUTERA-SARDO J，et al．Similar earlycharacteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2［J］．Orphanet J Rare Dis，2013，8（1）：80．DOI：10.1186/1750-1172-8-80.
［12］YELIN K，ALFONSO I，PAPAZIAN O，et al．Syndrome of Ohtahara［J］．Rev Neurol，1999，29（4）：340-342.
［13］PISANO T，NUMIS A L，HEAVIN S B，et al．Early and effective treatment of KCNQ2 encephalopathy［J］．Epilepsia，2015，56（5）：685-691．DOI：10.1111/epi.12984
［14］MALJEVIC S，NAROS G，YAL?IN ?，et al．Temperature and pharmacological rescue of a folding-defective，dominant-negative KV 7.2 mutation associated with neonatal seizures［J］．Hum Mutat，2011，32（10）：E2283-2293．DOI：10.1002/humu.21554.
［15］YAMASHITA S，CHIYONOBU T，YOSHIDA M，et al．Successful treatment with levetiracetam in a case of Ohtahara syndrome caused by STXBP1 mutation［J］．No To Hattatsu，2013，45（1）：64-66.
［16］KORFF CM，VULLIEMOZ S，PICARD F，et al．Ohtahara syndrome or early-onset west syndrome? A case with overlapping features and favorable response to vigabatrin［J］．Eur J Paediatr Neurol，2012，16（6）：753-757．DOI：10.1016/j.ejpn.2012.05.009.
［17］KRSEK P，SEBRONOVá V，PROCHáZKA T，et al．Successful treatment of Ohtahara syndrome with chloral hydrate［J］．Pediatr Neurol，2002，27（5）：388-391.
［18］CAMPISTOL J，GARCíA-GARCíA J J，LOBERA E，et al．The Ohtahara's syndrome：a special form of age-dependent epilepsy［J］．Rev Neurol，1997，25（138）：212-214.
［19］ISHII M，SHIMONO M，SENJU A，et al．The ketogenic diet as an effective treatment for Ohtahara syndrome［J］．No To Hattatsu，2011，43（1）：47-50.
［20］NACHANAKIAN A，HMAIMESS G，EL-HELOU A，et al．Early modified functional hemispherectomy in a young infant with Ohtahara syndrome and hemimegalencephaly［J］．J Child Neurol，2015，30（4）：522-526．DOI：10.1177/0883073814539558.
［21］KNEZEVIC-POGANCEV M.Ohtahara syndrome——early infantile epileptic encephalopathy［J］．Med Pregl，2008，61（11/12）：581-585.