Abstract：
BACKGROUND: VariousATP1A3variant-related diseases have been reported, including alternating hemiplegia of childhood; rapid-onset dystonia-parkinsonism; and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome. Moreover, a few cases of developmental and epileptic encephalopathy (DEE) with none of these symptoms have been reported. Here, we present a case of DEE with early childhood onset caused by anATP1A3variant that was effectively treated using corpus callosotomy (CC).
METHODS: At the age of 3 years, the patient developed epileptic spasms, complicated by generalized and focal aware tonic seizures. Based on the seizure type and electroencephalographic findings showing a generalized spike and waves as well as interictal left frontal-dominant spikes, combined generalized and focal epilepsy was diagnosed. Whole-exome sequencing revealed a de novo missense variant inATP1A3(c.2888G > A, p.Gly963Asp), which was classified as likely pathogenic. At the age of 5 years, CC for generalized tonic seizures resulted in seizure-freedom using two anti-seizure medications. Subsequently, the patient achieved better verbal development.
CONCLUSIONS: Early childhood onset DEE has not been reported in patients with ATP1A3 variants. Moreover, CC was extremely effective in our case. Although more research is needed to determine the etiology of epilepsy caused by theATP1A3 variant, the clinical course of DEE caused by the ATP1A3 variant is diverse and its prognosis may be improved in early childhood onset cases using aggressive control of epilepsy, such as CC.
METHODS: At the age of 3 years, the patient developed epileptic spasms, complicated by generalized and focal aware tonic seizures. Based on the seizure type and electroencephalographic findings showing a generalized spike and waves as well as interictal left frontal-dominant spikes, combined generalized and focal epilepsy was diagnosed. Whole-exome sequencing revealed a de novo missense variant inATP1A3(c.2888G > A, p.Gly963Asp), which was classified as likely pathogenic. At the age of 5 years, CC for generalized tonic seizures resulted in seizure-freedom using two anti-seizure medications. Subsequently, the patient achieved better verbal development.
CONCLUSIONS: Early childhood onset DEE has not been reported in patients with ATP1A3 variants. Moreover, CC was extremely effective in our case. Although more research is needed to determine the etiology of epilepsy caused by theATP1A3 variant, the clinical course of DEE caused by the ATP1A3 variant is diverse and its prognosis may be improved in early childhood onset cases using aggressive control of epilepsy, such as CC.
摘要：
背景：已经报道了各种ATP1A3变异相关疾病，包括儿童期交替偏瘫；快速发作的肌张力障碍-帕金森病；和小脑共济失调，无反射,pescavus,视神经萎缩,和感觉神经性听力损失综合征.此外，已报道了一些没有这些症状的发育性和癫痫性脑病（DEE）病例。这里,我们介绍了一例由ATP1A3变异体引起的儿童早期发病的DEE病例，该病例通过骨体切开术（CC）得到了有效治疗。
方法：3岁时，病人出现了癫痫性痉挛,并发全身性和局灶性强直性癫痫发作。根据癫痫发作类型和脑电图检查结果，显示出广泛的尖峰和波以及发作间左额叶优势尖峰，诊断为全身性和局灶性癫痫。全外显子组测序显示ATP1A3中存在一个从头错义变体（c.2888G>A，p.Gly963Asp)，被归类为可能致病。在5岁的时候，全身性强直性癫痫发作的CC使用两种抗癫痫药物导致癫痫发作自由。随后，患者获得了更好的言语发展。
结论：尚未报道ATP1A3变异患者的早期儿童发病DEE。此外，CC在我们的案例中非常有效。虽然需要更多的研究来确定ATP1A3变异引起的癫痫的病因，由ATP1A3变异引起的DEE的临床过程是多种多样的，在使用积极控制癫痫的早期儿童发作病例中，其预后可能会得到改善。比如CC。
方法：3岁时，病人出现了癫痫性痉挛,并发全身性和局灶性强直性癫痫发作。根据癫痫发作类型和脑电图检查结果，显示出广泛的尖峰和波以及发作间左额叶优势尖峰，诊断为全身性和局灶性癫痫。全外显子组测序显示ATP1A3中存在一个从头错义变体（c.2888G>A，p.Gly963Asp)，被归类为可能致病。在5岁的时候，全身性强直性癫痫发作的CC使用两种抗癫痫药物导致癫痫发作自由。随后，患者获得了更好的言语发展。
结论：尚未报道ATP1A3变异患者的早期儿童发病DEE。此外，CC在我们的案例中非常有效。虽然需要更多的研究来确定ATP1A3变异引起的癫痫的病因，由ATP1A3变异引起的DEE的临床过程是多种多样的，在使用积极控制癫痫的早期儿童发作病例中，其预后可能会得到改善。比如CC。
