Developmental and epileptic encephalopathies are a heterogeneous group of disorders characterized by early-onset, often severe epileptic seizures, EEG abnormalities, on a background of developmental impairment that tends to worsen as a consequence of epilepsy. DEEs may result from both non-genetic and genetic etiologies. Genetic DEEs have been associated with mutations in many genes involved in different functions including cell migration, proliferation, and organization, neuronal excitability, and synapse transmission and plasticity. Functional studies performed in different animal models and clinical trials on patients have contributed to elucidate pathophysiological mechanisms underlying many DEEs and explored the efficacy of different treatments. Here, we provide an extensive review of the phenotypic spectrum included in the DEEs, of the genetic determinants and pathophysiological mechanisms underlying these conditions. We also provide a brief overview of the most effective treatment now available and of the emerging therapeutic approaches.

中文翻译：

---

发育性和癫痫性脑病：从遗传异质性到表型连续体

发育性和癫痫性脑病是一组异质性疾病，其特征是早发性、通常是严重的癫痫发作、脑电图异常，其背景是由于癫痫导致的发育障碍往往会恶化。DEE 可能由非遗传和遗传病因引起。遗传性 DEE 与涉及不同功能的许多基因突变有关，包括细胞迁移、增殖和组织、神经元兴奋性以及突触传递和可塑性。在不同动物模型中进行的功能研究和对患者的临床试验有助于阐明许多 DEE 的病理生理机制，并探索不同治疗的功效。在这里，我们对 DEE 中包含的表型谱进行了广泛的审查，这些条件下的遗传决定因素和病理生理机制。我们还简要概述了目前最有效的治疗方法和新兴的治疗方法。