Universidad Militar Nueva Granada, Bogotá, Colombia.
Movement Disorders Specialist, Instituto Roosevelt, Bogotá, Colombia.
Epileptic Disord. 2024 Jun;26(3):332-340. doi: 10.1002/epd2.20220. Epub 2024 Mar 21.
Variants in the ATP1A2 gene exhibit a wide clinical spectrum, ranging from familial hemiplegic migraine to childhood epilepsies and early infantile developmental epileptic encephalopathy (EIDEE) with movement disorders. This study aims to describe the epileptology of three unpublished cases and summarize epilepsy features of the other 17 published cases with ATP1A2 variants and EIDEE.
Medical records of three novel patients with pathogenic ATP1A2 variants were retrospectively reviewed. Additionally, the PUBMED, EMBASE, and Cochrane databases were searched until December 2023 for articles on EIDEE with ATP1A2 variants, without language or publication year restrictions.
Three female patients, aged 6 months-10 years, were investigated. Epilepsy onset occurred between 5 days and 2 years, accompanied by severe developmental delay, intellectual disability, drug-resistant epilepsy, severe movement disorder, and recurrent status epilepticus. All individuals had pathogenic variants of the ATP1A2 gene (ATP1A2 c.720_721del (p.Ile240MetfsTer9), ATP1A2c.3022C > T (p.Arg1008Trp), ATP1A2 c.1096G > T (p.Gly366Cys), according to ACMG criteria. Memantine was p) rescribed to three patients, one with a reduction in ictal frequency, one with improvement in gait pattern, coordination, and attention span, and another one in alertness without significant side effects.
This study reinforces the association between ATP1A2 variants and a severe phenotype. All patients had de novo variants, focal motor seizures with impaired awareness as the primary type of seizure; of the 11 EEGs recorded, 10 presented a slow background rhythm, 7 multifocal interictal epileptiform discharges (IED), predominantly temporal IEDs, followed by frontal IED, as well as ten ictal recordings, which showed ictal onset from the same regions mentioned above. Treatment with antiseizure medication was generally ineffective, but memantine showed moderate improvement. Prospective studies are needed to enlarge the phenotype and assess the efficacy of NMDA receptor antagonist therapies in reducing seizure frequency and improving quality of life.
ATP1A2 基因突变表现出广泛的临床谱，从家族性偏瘫性偏头痛到儿童癫痫和伴有运动障碍的早发性婴儿癫痫性脑病（EIDEE）。本研究旨在描述 3 例未发表病例的癫痫学特征，并总结 17 例发表的伴有 ATP1A2 变异和 EIDEE 的病例的癫痫特征。
回顾性分析 3 例新型致病性 ATP1A2 变异患者的病历。此外，在 PUBMED、EMBASE 和 Cochrane 数据库中，检索了 2023 年 12 月前发表的关于伴有 ATP1A2 变异的 EIDEE 的文章，没有语言或出版年限的限制。
3 名女性患者年龄为 6 个月至 10 岁。癫痫发作发生在 5 天至 2 岁之间，伴有严重的发育迟缓、智力障碍、耐药性癫痫、严重运动障碍和反复癫痫持续状态。所有患者均携带 ATP1A2 基因突变（ATP1A2 c.720_721del（p.Ile240MetfsTer9）、ATP1A2c.3022C > T（p.Arg1008Trp）、ATP1A2 c.1096G > T（p.Gly366Cys），根据 ACMG 标准。3 名患者均接受了美金刚治疗，1 名患者癫痫发作频率降低，1 名患者步态、协调性和注意力范围改善，另 1 名患者警觉性提高，无明显副作用。
本研究进一步证实了 ATP1A2 变异与严重表型之间的关联。所有患者均携带新生变异，以意识障碍为主的局灶性运动性癫痫发作作为主要发作类型；11 份脑电图记录中，10 份背景节律缓慢，7 份局灶性发作间期癫痫样放电（IED），以颞叶 IED 为主，其次是额叶 IED，10 份发作记录显示发作起始于上述相同区域。抗癫痫药物治疗通常无效，但美金刚治疗有中度改善。需要前瞻性研究来扩大表型，并评估 NMDA 受体拮抗剂治疗在降低癫痫发作频率和提高生活质量方面的疗效。
