PCDH19基因单错义变异相关性女性癫间(附3例报告及文献复习)

Three Cases of Female Epilepsy Associated with Single Missense Variant of the PCDH19 Gene and the Literature Review

目的总结PCDH19基因单错义变异导致女性癫间患儿的临床表型特点。方法收集2018年1月至2023年3月河北省儿童医院就诊的3例携带PCDH19基因单错义变异致癫间女性患儿的临床资料;检索并筛选存在PCDH19基因单错义变异女性癫间患儿相关文献,结合临床表型特点进行总结分析。结果3例PCDH19基因单错义变异致女性癫间患儿起病年龄分布于8月龄^(+10d)至1岁+2月龄^(+23d);癫间发作类型多样,口服左乙拉西坦抗癫间治疗效果均佳;发育为正常至重度迟缓;脑电图均为棘波、棘慢波发放。突变位点分别为c.1835G>Ap.Arg612His、c.418G>A/p.Glu140Lys、c.1142A>Gp.Asn381Ser。检索数据库文献符合要求的相关病例与本研究3例患儿共计160例。起病年龄:出生后1 d至8岁;癫间发作形式多样;癫间发作前发育异常8/18例。癫间发作前诱因:热敏性63/97例;智力发育异常(70/113例)、自闭症(27/63例)、语言落后(23/42例)、行为异常(22/34例)。有精神疾病(10/13例)。脑电图检查:35/43例异常,其中尖波发放10例,7例有棘波、棘慢波发放特点。头颅MRI检查:以大脑发育不良最多、脑萎缩7例。治疗:使用>3种抗癫间药物82/129例。结论PCDH19基因单错义变异所致女性癫间患儿起病年龄跨度大,1 d至学龄期均可发病,部分癫间发作前发育可异常;大多有热敏性诱因,以局灶性发作常见,发病后大多出现智力和语言能力下降,可出现自闭、行为异常、精神疾病等;头颅MRI多为脑发育不良、萎缩,脑电图多为大脑单侧放电,可见尖波、棘波、棘慢波发放特点;耐药者多见。

Aim To summarize the clinical phenotypic characteristics of female children with epilepsy due to single missense variant of PCDH19 gene.Methods Clinical data of three female children with epilepsy caused by single missense variant of PCDH19 gene were collected from January 2018 to March 2023 in Hebei Children's Hospital,and the relevant literature on female children with epilepsy caused by single missense variant of PCDH19 gene was searched and analyzed in combination with the clinical phenotypic characteristics.Results The three children with female epilepsy caused by single missense variant of PCDH19 gene had the age of onset from 8 months+10 d to 1 year+2 months+23d.There were many types of seizures.The effects of oral antiepileptic treatment with levetiracetam were all good.The development ranged from normal to severely retarded.The electroencephalograms were all spike-wave and spiking slow-wave discharges.The mutation loci were respectively c.1835G>Ap.Arg612His,c.418G>A/p.Glu140Lys,c.1142A>Gp.Asn381Ser.A total of 160 cases were found in the database and 3 children in our group.Their ages of onset were 1 d after birth to 8 years old,with a variety of forms of seizures,pre-seizure dysplasia 8/18 cases.There are some pre-seizure triggers in the cases:thermo sensitivity 63/97 cases;dysgenesis of intellect 70/113 cases;autism 27/63 cases;language lag 23/42 cases;abnormal behavior 22/34 cases.10/13 cases had psychiatric disorders.Electroencephalogram(EEG)examination showed that 35/43 cases were abnormal,of which 10 cases had sharp wave emission and 7 cases had spike wave and slow wave emission.Cranial MRI examination showed that most cases had brain dysplasia and brain atrophy in 7 cases.82/129 patients were treated with more than 3 antiepileptic drugs.Conclusion Female children with epilepsy caused by single missense variant of PCDH19 gene have a wide range of age of onset,from 1 d to school age,some of them may have abnormal development before seizure,most of them have heat-sensitive triggers,and focal seizures are common,and most of them suffer from decreased intelligence and language ability,and may have autism,behavioral abnormality,and psychiatric disorders.Most of them are unilateral discharges in the brain,which can be characterized by sharp waves,spike waves and slow spike waves,and treatment-resistant people are common.