Marzin Pauline, Mignot Cyril, Dorison Nathalie, Dufour Louis, Ville Dorothée, Kaminska Anna, Panagiotakaki Eleni, Dienpendaele Anne-Sophie, Penniello Marie-José, Nougues Marie-Christine, Keren Boris, Depienne Christel, Nava Caroline, Milh Mathieu, Villard Laurent, Richelme Christian, Rivier Clotilde, Whalen Sandra, Heron Delphine, Lesca Gaëtan, Doummar Diane
APHP, Département de Génétique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; Centre de Référence Déficience Intellectuelle de Causes Rares, Paris, France; Sorbonne Université, GRC, Déficience Intellectuelle et Autisme, APHP, Groupe Hospitalier Pitié-Salpêtrière, F-75012 Paris, France.
APHP, Service de Neurologie Pédiatrique, Hôpital Armand Trousseau, Paris, France; APHP, Centre de Référence des Mouvements Anormaux de l'Enfant, Hôpital Armand Trousseau, Paris, France.
Brain Dev. 2018 Oct;40(9):768-774. doi: 10.1016/j.braindev.2018.05.008. Epub 2018 May 31.
Heterozygous mutations in the ATP1A3 gene are responsible for various neurological disorders, ranging from early-onset alternating hemiplegia of childhood to adult-onset dystonia-parkinsonism. Next generation sequencing allowed the description of other phenotypes, including early-onset epileptic encephalopathy in two patients. We report on three more patients carrying ATP1A3 mutations with a close phenotype and discuss the relationship of this phenotype to alternating hemiplegia of childhood.
The patients' DNA underwent next generation sequencing. A retrospective analysis of clinical case records is reported.
Each of the three patients had an unreported heterozygous de novo sequence variant in ATP1A3. These patients shared a similar phenotype characterized by early-onset attacks of movement disorders, some of which proved to be epileptic, and severe developmental delay. (Hemi)plegic attacks had not been considered before genetic testing.
Together with the two previously reported cases, our patients confirm that ATP1A3 mutations are associated with a phenotype combining features of early-onset encephalopathy, epilepsy and dystonic fits, as in the most severe forms of alternating hemiplegia of childhood, but in which (hemi)plegic attacks are absent or only suspected retrospectively.
ATP1A3基因的杂合突变可导致多种神经系统疾病，范围从儿童期早发性交替性偏瘫到成人期肌张力障碍 - 帕金森综合征。二代测序使其他表型得以描述，包括两名患者的早发性癫痫性脑病。我们报告另外三名携带ATP1A3突变且具有相似表型的患者，并讨论该表型与儿童期交替性偏瘫的关系。
对患者的DNA进行二代测序。报告对临床病例记录的回顾性分析。
三名患者中的每一位在ATP1A3基因中都有一个未报告的杂合新发序列变异。这些患者具有相似的表型，其特征为早发性运动障碍发作，其中一些被证实为癫痫发作，以及严重的发育迟缓。在基因检测之前未考虑过（半）瘫痪发作。
与之前报道的两例病例一起，我们的患者证实ATP1A3突变与一种表型相关，该表型结合了早发性脑病、癫痫和肌张力障碍发作的特征，如同儿童期最严重形式的交替性偏瘫，但其中（半）瘫痪发作不存在或仅在回顾性分析时被怀疑。
