Alternating Hemiplegia of Childhood (AHC) is a rare disorder characterized by frequent, transient attacks of hemiplegia involving either side of the body or both in association to several other disturbances including dystonic spells, abnormal ocular movements, autonomic manifestations, epileptic seizures and cognitive impairment. The clinical manifestations usually start before the age of 18 months. Two forms of the disorder known as AHC-1 (MIM#104290) and AHC-2 (MIM#614820) depends on mutations in ATP1A2 and ATP1A3 genes respectively, with over 75% of AHC caused by a mutation in the ATP1A3 gene. Herewith, we report serial clinical follow-up data of monozygotic (MZ) twin sisters, who presented in early life bath-induced dystonia, signs of acute encephalopathy at the age of 2 years, hemiplegic spells, and motor dysfunction after the age of 3 years, and in young/adult frequent episodes of headache with drastic reduction of paroxysmal motor attacks. The molecular analysis revealed a known pathogenic variant p.Asn773Ser (rs606231437) in ATP1A3 gene associated with an unusual and moderate AHC-2 phenotype, with mild cognitive impairment and lack of epilepsy. The aim of this study is to analyze the clinical phases of the MZ twins, and to investigate the novel genotype–phenotype correlation.

儿童交替性偏瘫（AHC）是一种罕见的疾病，其特征在于偏瘫的频繁，短暂发作涉及身体的任一侧或双方，同时伴有其他几种不适，包括肌张力异常，眼球运动异常，自主神经表现，癫痫发作和认知障碍。临床表现通常在18个月大之前开始。称为AHC-1（MIM＃104290）和AHC-2（MIM＃614820）的两种形式的疾病分别取决于ATP1A2和ATP1A3基因的突变，其中超过75％的AHC是由ATP1A3突变引起的基因。据此，我们报告了单卵双生（MZ）双胞胎姐妹的系列临床随访数据，这些双胞胎姐妹在生命早期浴诱发的肌张力障碍，2岁时出现急性脑病的体征，偏瘫和3岁以后的运动功能障碍年来，在年轻人/成年人中，头痛发作频繁，发作性运动发作明显减少。分子分析揭示了ATP1A3基因中已知的致病性变体p.Asn773Ser（rs606231437）与异常和中等的AHC-2表型有关，伴有轻度认知障碍和癫痫发作。本研究的目的是分析MZ双胞胎的临床阶段，并研究新的基因型与表型的相关性。