Pathogenic variants in ATP1A2, a gene encoding the α subunit of the Na,K-ATPase, cause familial hemiplegic migraine type 2 (FHM2). In contrast, pathogenic variants in ATP1A3, an ATP1A2 paralog, cause alternating hemiplegia of childhood (AHC), a severe neurodevelopmental disorder with infantile onset hemiplegic attacks, seizures, dystonia, chorea and developmental delay. Despite high sequence homology with ATP1A3, ATP1A2 variants rarely associate with severe phenotypes resembling those linked to ATP1A3. Here we describe two unrelated patients with infantile onset hemiplegic attacks, refractory epilepsy, movement disorders, abnormal eye movements and truncal ataxia with a shared de novo variant in ATP1A2, c.2438T > A (p.Met813Lys). The variant is not found in population databases, is predicted to be damaging by in silico analysis, and affects a highly conserved residue. Both patients experienced severe attacks with unilateral cerebral edema followed by sustained, stepwise regression. This report highlights the need to sequence ATP1A2 in the workup of patients with features of AHC that do not fulfill AHC diagnostic criteria.

ATP1A2（一种编码Na，K-ATPase的α亚基的基因）中的致病变体引起家族性偏瘫偏头痛2型（FHM2）。相比之下，ATP1A3（一种ATP1A2旁系同源物）中的致病变异导致儿童交替性偏瘫（AHC），这是一种严重的神经发育障碍，伴有婴儿发作性偏瘫发作，癫痫发作，肌张力障碍，舞蹈病和发育迟缓。尽管与ATP1A3具有很高的序列同源性，ATP1A2的变异很少与类似于ATP1A3的严重表型相关。在这里，我们描述了两名不相关的婴儿发作性偏瘫发作，难治性癫痫，运动障碍，异常眼球运动和躯干共济失调的患者，ATP1A2中的从头变异，c.2438T> A（p.Met813Lys）。该变异体未在种群数据库中找到，通过计算机分析预计会对其造成破坏，并影响高度保守的残基。两名患者均遭受严重发作，伴有单侧脑水肿，然后持续逐步消退。该报告强调了在具有不符合AHC诊断标准的AHC特征的患者的检查中需要对ATP1A2进行测序。