De Rinaldis Marta, Giorda Roberto, Trabacca Antonio
Scientific Institute IRCCS "E. Medea", Unit for Severe Disabilities in Developmental Age and Young Adults (Developmental Neurology and Neurorehabilitation), Brindisi, Italy.
Scientific Institute IRCCS "E. Medea", Molecular Biology Laboratory, Bosisio Parini, LC, Italy.
Brain Dev. 2020 Jan;42(1):77-82. doi: 10.1016/j.braindev.2019.08.001. Epub 2019 Aug 30.
Mutations in the elongation factor 1 alpha 2 (EEF1A2) gene have been recently shown to cause epileptic encephalopathy (MIM # 616409 EIEE33) associated with neurodevelopmental disorders such as intellectual disability, autistic spectrum disorder, hypotonia and dysmorphic facial features. EEF1A2 protein is involved in protein synthesis, suppression of apoptosis, regulation of actin function and cytoskeletal structure. To date, only sixteen patients with EEF1A2 mutations have been reported.
We described a new case, a boy with severe intellectual disability with absent speech, autistic spectrum disorder, mild dysmorphic facial features, failure to thrive and epilepsy associated to a de novo heterozygous missense mutation in EEF1A2 (c.364G>A; p.Glu122Lys) identified by next generation sequencing; it was already reported in other studies. Most clinical features are shared by all individuals with EEF1A2 mutation, but unlike others reports our patient showed a mild epileptic phenotype: epilepsy developed in late infancy and was well-controlled with antiepileptic drugs. Moreover, at the onset of epilepsy, interictal wake/sleep electroencephalograms showed typical pattern that disappeared with age.
This report focused that EEF1A2 mutations should be considered not only in patients with epileptic encephalopathy, but also in those with less severe epilepsy. A typical EEG pattern may be a biomarker for EEF1A2 mutation, but further investigations and longitudinal clinical observations are required.
最近研究表明，延伸因子1α2（EEF1A2）基因突变可导致与神经发育障碍相关的癫痫性脑病（MIM # 616409，EIEE33），这些神经发育障碍包括智力残疾、自闭症谱系障碍、肌张力减退和面部畸形特征。EEF1A2蛋白参与蛋白质合成、细胞凋亡抑制、肌动蛋白功能调节和细胞骨架结构调节。迄今为止，仅报道了16例EEF1A2基因突变患者。
我们描述了一个新病例，一名患有严重智力残疾且无语言能力、自闭症谱系障碍、轻度面部畸形特征、发育不良和癫痫的男孩，通过下一代测序鉴定其EEF1A2基因存在新生杂合错义突变（c.364G>A；p.Glu122Lys）；该突变已在其他研究中报道过。所有EEF1A2基因突变个体都有大多数临床特征，但与其他报告不同的是，我们的患者表现出轻度癫痫表型：癫痫在婴儿晚期发病，使用抗癫痫药物可得到良好控制。此外，在癫痫发作时，发作间期清醒/睡眠脑电图显示出典型模式，该模式随年龄增长而消失。
本报告强调，不仅癫痫性脑病患者，而且癫痫症状较轻的患者也应考虑EEF1A2基因突变。典型的脑电图模式可能是EEF1A2基因突变的生物标志物，但还需要进一步研究和长期临床观察。
