Unravelling Disease Mechanisms Causing Seizures and Cognitive Dysfunction in Early Infantile Epileptic Encephalopathy (EIEE)

许多癫痫疾病存在于婴儿在生命的第一年，可悲的是，这些婴儿中有很大一部分有非常频繁的癫痫发作（对药物没有反应），发育进展极差，过早死亡的风险很高。在这些患者中，大约有一半的原因无法确定，并且很可能许多人都有潜在的遗传原因，其中一个错误的基因是导致婴儿痉挛的原因。我最近在这些孩子中发现了一个新的“缺陷基因”。这个项目将提高我们的能力，为其中一些有严重痉挛儿童的家庭提供答案。这也将导致更好地了解导致癫痫的疾病机制。我计划调查一个新发现的基因在儿童严重的早发性癫痫发作，并回答以下问题：1。这种基因突变在早期癫痫患者中有多常见？2.这个基因的缺陷是如何导致癫痫的？3.这种基因的缺陷如何影响学习、记忆和行为，这些都是早发性癫痫儿童的重要问题？基因检测的结果将在短期内提供给家庭。有助于这种类型的早发性癫痫的一些机制将在中期阐明。从长远来看，我们计划利用这些知识来尝试寻找新的药物和其他治疗方法，以改善这些患者的癫痫发作和长期预后。

Many epilepsy disorders present in babies in the first year of life and sadly, a significant proportion of these infants have very frequent seizures (which do not respond to medication), make extremely poor developmental progress and have a high risk of premature death. In around half of these patients, a cause cannot be identified and it is likely that many will have an underlying genetic cause where a faulty gene is responsible for the baby's fits. I have recently discovered a new "faulty gene" in some of these children. This project will improve our ability to provide answers for some of these families with children with severe fits. It will also lead to a better understanding of the disease mechanisms that lead to epilepsy.I plan to investigate a newly discovered gene in children with severe early onset seizures and to answer the following questions:1. How common are mutations in this gene in patients with early epilepsy?2. How do faults in this gene cause epilepsy?3. How do faults in this gene impact learning, memory and behaviour, which are all important problems for children with early onset epilepsy?Results of the genetic testing will be available for families in the short term. Some of the mechanisms contributing to this type of early onset epilepsy will be elucidated in the medium term. In the longer term, we plan use this knowledge to try and find new drugs and other treatments to try and improve the seizures and long term outcome for these patients.