Hanzlik Emily, Klinger Sarah A, Carson Robert, Duis Jessica
Pediatric Neurology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
Medical Genetics & Genomic Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
J Clin Sleep Med. 2020 Apr 15;16(4):591-595. doi: 10.5664/jcsm.8284.
Angelman syndrome (AS) is a rare neurodevelopmental disorder that is characterized by developmental delay, intellectual disability, seizures, a characteristic happy personality, gait ataxia, tremulousness of the limbs, microcephaly, and anxiety. Severe sleep disturbances with the diminished need for sleep and abnormal sleep-wake cycles are seen in up to 90% of patients with AS. AS is caused by absent maternal expression of the gene UBE3A located in the 15q11.2-q13 locus. We hypothesized that selective antagonism of 5-HT₂ and 5-HT₃ serotonin receptors with mirtazapine would benefit sleep disturbances in patients with AS.
Institutional Review Board approval was obtained at Vanderbilt University Medical Center. Medical records of individuals seen in the Comprehensive Angelman Syndrome clinic were retrospectively reviewed to determine the use of mirtazapine for disordered sleep. Parents were asked to respond to a survey to assess the phenotypic features of sleep and behavioral disturbances in AS. They were asked about the use of medications for sleep, focusing on the benefits and risks of mirtazapine.
A cohort of 8 individuals with AS, ranging in age from 3 to 16 years old with histories of sleep challenges, were treated with 3.75 to 30 mg of mirtazapine at bedtime for 0 to 36 weeks. Nocturnal awakenings were the most common sleep challenge reported. Seven of eight patients reported benefits from mirtazapine, including increased total sleep time, decreased nocturnal awakenings, and decreased time to fall asleep. The most significant side effects of mirtazapine were hyperphagia and weight gain.
Individuals with AS have abnormal sleep-wake cycles and a high unmet medical need. Mirtazapine helped with sleep onset and nighttime awakenings in 7 of 8 patients, with 2 patients reporting a positive benefit with respect to behavior. These data suggest that mirtazapine may be considered for the treatment of sleep difficulties in patients with AS who remain refractory to more conventional therapies. Weight gain was a common side-effect and led to discontinuation of treatment in 1 patient.
天使综合征（AS）是一种罕见的神经发育障碍，其特征包括发育迟缓、智力残疾、癫痫发作、特有的快乐性格、步态共济失调、肢体震颤、小头畸形和焦虑。高达90%的AS患者存在严重的睡眠障碍，表现为睡眠需求减少和异常的睡眠-觉醒周期。AS是由位于15q11.2-q13位点的UBE3A基因的母源表达缺失引起的。我们假设米氮平对5-羟色胺2型（5-HT₂）和5-羟色胺3型（5-HT₃）血清素受体的选择性拮抗作用将改善AS患者的睡眠障碍。
获得范德比尔特大学医学中心机构审查委员会的批准。对综合天使综合征诊所就诊个体的病历进行回顾性审查，以确定米氮平用于睡眠障碍的情况。要求家长对一项调查做出回应，以评估AS患者睡眠和行为障碍的表型特征。询问他们关于睡眠药物的使用情况，重点是米氮平的益处和风险。
一组8名年龄在3至16岁之间有睡眠问题病史的AS患者，在睡前服用3.75至30毫克米氮平，持续0至36周。夜间觉醒是报告的最常见睡眠问题。8名患者中有7名报告米氮平有益处，包括总睡眠时间增加、夜间觉醒减少和入睡时间缩短。米氮平最显著的副作用是食欲亢进和体重增加。
AS患者存在异常的睡眠-觉醒周期，且有很大的未满足医疗需求。米氮平帮助8名患者中的7名入睡和减少夜间觉醒，2名患者报告在行为方面有积极益处。这些数据表明，对于对更传统疗法仍有抵抗的AS患者，可考虑使用米氮平治疗睡眠困难。体重增加是常见的副作用，导致1名患者停止治疗。
