PDF(Pubmed)
Abstract：
Rett Syndrome (RTT) is a rare and severe X-linked developmental brain disorder that occurs primarily in females, with a ratio of 1:10.000. De novo mutations in the Methyl-CpG Binding protein 2 (MECP2) gene on the long arm of X chromosome are responsible for more than 95% cases of classical Rett. In the remaining cases (atypical Rett), other genes are involved such as the cyclin-dependent kinase-like 5 (CDKL5) and the forkhead box G1 (FOXG1). Duplications of the MECP2 locus cause MECP2 duplication syndrome (MDS) which concerns about 1% of male patients with intellectual disability. Sleep disorders are common in individuals with intellectual disability, while the prevalence in children is between 16 and 42%. Over 80% of individuals affected by RTT show sleep problems, with a higher prevalence in the first 7 years of life and some degree of variability in correlation to age and genotype. Abnormalities in circadian rhythm and loss of glutamate homeostasis play a key role in the development of these disorders. Sleep disorders, epilepsy, gastrointestinal problems characterize CDKL5 Deficiency Disorder (CDD). Sleep impairment is an area of overlap between RTT and MECP2 duplication syndrome along with epilepsy, regression and others. Sleep dysfunction and epilepsy are deeply linked. Sleep deprivation could be an aggravating factor of epilepsy and anti-comitial therapy could interfere in sleep structure. Epilepsy prevalence in atypical Rett syndrome with severe clinical phenotype is higher than in classical Rett syndrome. However, RTT present a significant lifetime risk of epilepsy too. Sleep disturbances impact on child\'s development and patients\' families and the evidence for its management is still limited. The aim of this review is to analyze pathophysiology, clinical features, the impact on other comorbidities and the management of sleep disorders in Rett syndrome and Rett-related syndrome.
摘要：
Rett综合征（RTT）是一种罕见且严重的X连锁发育性脑部疾病，主要发生在女性中，比例为1:10.000。X染色体长臂上的甲基-CpG结合蛋白2（MECP2）基因的从头突变导致超过95％的经典Rett病例。在其余病例中（非典型Rett），涉及其他基因，例如细胞周期蛋白依赖性激酶样5（CDKL5）和叉头盒G1（FOXG1）。MECP2基因座的重复引起MECP2重复综合征（MDS），约有1％的智障男性患者。睡眠障碍在智力障碍患者中很常见，而儿童的患病率在16%到42%之间。超过80％的受RTT影响的人表现出睡眠问题，在生命的前7年患病率较高，并且与年龄和基因型相关的一定程度的变异性。昼夜节律的异常和谷氨酸稳态的丧失在这些疾病的发展中起关键作用。睡眠障碍,癫痫,胃肠道问题是CDKL5缺乏症（CDD）的特征。睡眠障碍是RTT和MECP2重复综合征与癫痫的重叠区域，回归和其他。睡眠功能障碍和癫痫有很深的联系。睡眠剥夺可能是癫痫的加重因素，而抗替代疗法可能会干扰睡眠结构。具有严重临床表型的非典型Rett综合征的癫痫患病率高于经典Rett综合征。然而,RTT也呈现癫痫的显著终生风险。睡眠障碍对儿童发育和患者家庭的影响及其管理的证据仍然有限。这篇综述的目的是分析病理生理学，临床特征,Rett综合征和Rett相关综合征对其他合并症和睡眠障碍管理的影响。
