Tascini Giorgia, Dell'Isola Giovanni Battista, Mencaroni Elisabetta, Di Cara Giuseppe, Striano Pasquale, Verrotti Alberto
Department of Pediatrics, University of Perugia, Perugia, Italy.
Pediatric Neurology and Muscular Diseases Unit, IRCCS "G. Gaslini" Institute, Genoa, Italy.
Front Neurol. 2022 Mar 1;13:817195. doi: 10.3389/fneur.2022.817195. eCollection 2022.
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. 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.
雷特综合征(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,发病率约为1:10000。位于X染色体长臂上的甲基CpG结合蛋白2(MECP2)基因突变导致超过95%的典型雷特综合征病例。在其余病例(非典型雷特综合征)中,还涉及其他基因,如细胞周期蛋白依赖性激酶样5(CDKL5)和叉头框G1(FOXG1)。MECP2基因座的重复会导致MECP2重复综合征(MDS),约1%的男性智力残疾患者受其影响。睡眠障碍在智力残疾个体中很常见,儿童中的患病率在16%至42%之间。超过80%的雷特综合征患者存在睡眠问题,在生命的前7年患病率更高,且在一定程度上与年龄和基因型相关。昼夜节律异常和谷氨酸稳态失衡在这些疾病的发生发展中起关键作用。睡眠障碍、癫痫、胃肠道问题是CDKL5缺乏症(CDD)的特征。睡眠障碍是雷特综合征和MECP2重复综合征的重叠领域之一,此外还有癫痫、退化等。睡眠功能障碍与癫痫密切相关。睡眠剥夺可能是癫痫的加重因素,而抗癫痫治疗可能会干扰睡眠结构。具有严重临床表型的非典型雷特综合征的癫痫患病率高于典型雷特综合征。然而,雷特综合征患者一生中也有患癫痫的重大风险。睡眠障碍会影响儿童的发育和患者家庭,而针对其治疗的证据仍然有限。本综述的目的是分析雷特综合征和雷特相关综合征中睡眠障碍的病理生理学、临床特征、对其他合并症的影响以及治疗方法。