In 1965, Dr Harry Angelman reported a neurodevelopmental disorder affecting three unrelated children who had similar symptoms: brachycephaly, mental retardation, ataxia, seizures, protruding tongues, and remarkable paroxysms of laughter. Over the past 50 years, the disorder became Angelman's namesake and symptomology was expanded to include hyper‐activity, stereotypies, and severe sleep disturbances. The sleep disorders in many Angelman syndrome (AS) patients are broadly characterized by difficulty falling and staying asleep at night. Some of these patients sleep less than 4 hours a night and, in most cases, do not make up this lost sleep during the day—leading to the speculation that AS patients may “need” less sleep. Most AS patients also have severely reduced levels of melatonin, a hormone produced by the pineal gland exclusively at night. This nightly pattern of melatonin production is thought to help synchronize internal circadian rhythms and promote nighttime sleep in humans and other diurnal species. It has been proposed that reduced melatonin levels contribute to the sleep problems in AS patients. Indeed, emerging evidence suggests melatonin replacement therapy can improve sleep in many AS patients. However, AS mice show sleep problems that are arguably similar to those in humans despite being on genetic backgrounds that do not make melatonin. This suggests the hypothesis that the change in nighttime melatonin may be a secondary factor rather than the root cause of the sleeping disorder. The goals of this review article are to revisit the sleep and melatonin findings in both AS patients and animal models of AS and discuss what AS may tell us about the underlying mechanisms of, and interplay between, melatonin and sleep.

中文翻译：

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Angelman 综合征和褪黑激素：它们能教给我们什么关于睡眠调节的知识

1965 年，Harry Angelman 博士报告了一种影响三名具有相似症状的无关儿童的神经发育障碍：短头畸形、智力迟钝、共济失调、癫痫发作、突出的舌头和明显的大笑。在过去的 50 年里，这种疾病成为 Angelman 的同名病，症状也扩大到包括多动、刻板印象和严重的睡眠障碍。许多 Angelman 综合征 (AS) 患者的睡眠障碍的广泛特征是难以入睡和晚上难以入睡。其中一些患者每晚的睡眠时间少于 4 小时，并且在大多数情况下，白天的睡眠不足，这导致人们猜测 AS 患者可能“需要”更少的睡眠。大多数 AS 患者的褪黑激素水平也严重降低，褪黑激素是一种仅在夜间由松果体产生的激素。这种褪黑激素产生的夜间模式被认为有助于同步内部昼夜节律并促进人类和其他昼夜物种的夜间睡眠。有人提出降低褪黑激素水平会导致 AS 患者的睡眠问题。事实上，新出现的证据表明褪黑激素替代疗法可以改善许多 AS 患者的睡眠。然而，尽管具有不产生褪黑激素的遗传背景，但 AS 小鼠的睡眠问题可以说与人类相似。这表明夜间褪黑激素的变化可能是次要因素，而不是睡眠障碍的根本原因。这篇评论文章的目的是重新审视 AS 患者和 AS 动物模型中的睡眠和褪黑激素的发现，并讨论 AS 可能告诉我们的潜在机制，