Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
Regional Epilepsy Centre, Great Metropolitan Hospital "Bianchi-Melacrino-Morelli", Reggio, Calabria, Italy.
Expert Rev Clin Pharmacol. 2022 Jul;15(7):843-850. doi: 10.1080/17512433.2022.2109463. Epub 2022 Aug 10.
Angelman syndrome (AS) is a neurogenetic disorder due to deficient expression of the maternal copy of the UBE3A gene, which encodes ubiquitin ligase E3A protein. Severe developmental delay, seizures and other neurological disorders characterize AS.
In this review, we focus on a comprehensive therapeutic approach to the most disabling neurological manifestations of AS: epilepsy, sleep disturbances, behavioral and movement disorders. Articles were identified through PubMed and Google Scholar up to October 2021.
Evidence for the treatment of neurological manifestations in AS mainly derives from poor quality studies (case reports, small case series, expert opinions). Seizures can be polymorphic and includes atypical absences, myoclonic, generalized tonic-clonic, unilateral clonic, or atonic attacks. Sodium valproate, levetiracetam, and benzodiazepines are the most commonly used anti-seizure medications. Melatonin or mirtazapine seem to improve sleep quality. Antipsychotics, antidepressants, and anxiolytics have been proposed for the treatment of behavioral manifestations, but no evidence-based studies are available. Non-pharmacological approach may also be useful. Mild dystonia is common but usually does not significantly impact patients' motor performances. Well-conducted clinical trials aimed to evaluate treatment of neurological complications of AS are warranted. Gene and molecular precision therapies represent a fascinating area of research in the future.
天使综合征（AS）是一种神经遗传疾病，由于母源 UBE3A 基因表达缺陷，导致泛素连接酶 E3A 蛋白缺失。严重的发育迟缓、癫痫发作和其他神经功能障碍是 AS 的特征。
在这篇综述中，我们重点关注对 AS 最具致残性的神经表现的全面治疗方法：癫痫、睡眠障碍、行为和运动障碍。文章通过 PubMed 和 Google Scholar 检索至 2021 年 10 月。
AS 神经表现治疗的证据主要来自低质量研究（病例报告、小病例系列、专家意见）。癫痫发作可能呈多形性，包括非典型失神发作、肌阵挛发作、全面强直-阵挛发作、单侧阵挛发作或强直-阵挛发作。丙戊酸钠、左乙拉西坦和苯二氮䓬类药物是最常用的抗癫痫药物。褪黑素或米氮平似乎可以改善睡眠质量。抗精神病药、抗抑郁药和抗焦虑药已被提议用于治疗行为表现，但目前尚无基于证据的研究。非药物治疗方法也可能有用。轻度的肌张力障碍很常见，但通常不会显著影响患者的运动表现。需要进行精心设计的临床试验，以评估 AS 神经并发症的治疗方法。基因和分子精准治疗代表了未来一个引人入胜的研究领域。
