Abstract：
Dynamin-1 (DNM1) is involved in synaptic vesicle recycling, and DNM1 mutations can lead to developmental and epileptic encephalopathy. The neuroimaging of DNM1 encephalopathy has not been reported in detail. We describe a severe phenotype of DNM1 encephalopathy showing characteristic neuroradiological features. In addition, we reviewed previously reported cases who have DNM1 pathogenic variants with white matter abnormalities. Our case presented drug-resistant seizures from 1 month of age and epileptic spasms at 2 years of age. Brain MRI showed no progression of myelination, progression of diffuse cerebral atrophy, and a thin corpus callosum. Proton magnetic resonance spectroscopy showed a decreased N-acetylaspartate peak and diffusion tensor imaging presented with less pyramidal decussation. Whole-exome sequencing revealed a recurrent de novo heterozygous variant of DNM1. So far, more than 50 cases of DNM1 encephalopathy have been reported. Among these patients, delayed myelination occurred in two cases of GTPase-domain DNM1 encephalopathy and in six cases of middle-domain DNM1 encephalopathy. The neuroimaging findings in this case suggest inadequate axonal development. DNM1 is involved in the release of synaptic vesicles with the inhibitory transmitter GABA, suggesting that GABAergic neuron dysfunction is the mechanism of refractory epilepsy in DNM1 encephalopathy. GABA-mediated signaling mechanisms play important roles in axonal development and GABAergic neuron dysfunction may be cause of white matter abnormalities in DNM1 encephalopathy.
摘要：
Dynamin-1（DNM1）参与突触小泡再循环，DNM1突变可导致发育性脑病和癫痫性脑病。DNM1脑病的神经影像学尚未详细报道。我们描述了DNM1脑病的严重表型，显示出特征性的神经放射学特征。此外,我们回顾了以前报道的DNM1致病变种伴白质异常的病例.我们的病例从1个月大开始出现抗药性癫痫发作，2岁时出现癫痫性痉挛。脑部MRI显示无髓鞘形成进展,弥漫性脑萎缩的进展，和一个薄的胼胝体。质子磁共振波谱显示N-乙酰天冬氨酸峰降低，扩散张量成像呈现较小的锥体截流。全外显子组测序揭示了DNM1的从头杂合变异体。到目前为止,已经报道了50多例DNM1脑病。在这些患者中,2例GTP酶结构域DNM1脑病和6例中域DNM1脑病均发生髓鞘形成延迟.这种情况下的神经影像学发现表明轴突发育不足。DNM1与抑制性递质GABA一起参与突触小泡的释放，提示GABA能神经元功能障碍是DNM1脑病难治性癫痫的机制。GABA介导的信号传导机制在轴突发育中起重要作用，GABA能神经元功能障碍可能是DNM1脑病白质异常的原因。
