Sleep problems in Rett syndrome animal models: A systematic review

Zhang, Xinyan; Lin, Jian‐Sheng; Spruyt, Karen

doi:10.1002/jnr.24730

Cited by 13 publications

(13 citation statements)

References 107 publications

(320 reference statements)

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“…Disruption in sleep continuity and efficacy are confirmed. Sleep abnormalities and an increased number of nocturnal awakenings were observed in all animal models ( 90 , 132 – 134 ). Sleep duration was investigated by three studies, that showed an unchanged percentage duration of sleep during the day, but Johnston et al reported a decrease of REM sleep cycles in mutants ( 135 , 136 ).…”

Section: Sleep Disorders In Rett Syndrome and Rett-related Syndromementioning

confidence: 95%

“…A possible role of MECP2 has emerged in the circadian system and a possible correlation with sleep problems observed in RTT patients (128,129). Alteration in the circadian rhythms have been found also in the mouse model of CDKL5 deficiency disorders (130) (90,103,135). This could be traced back to the glutamatergic alteration found in MECP2-null mice, in which a biphasic trend in the expression of ionotropic glutamate N methyl-D-aspartate receptors (NMDARs) in the frontal cortex was shown, with an initial increased density in the young stage, progressively decreasing.…”

Section: Sleep Research In Both Animal Models and Humansmentioning

confidence: 97%

“…Nevertheless, highly fragmentated sleep and circadian rhythm alterations have been found in animal models (mutated models of cynomolgus monkeys, Drosophila, and mice). Evidence showed how MECP2, but also CDKL5 and FOXG1, might be implicated in the proper functioning of specific brain areas and neurotransmitters involved in the sleep-wake cycle ( 39 , 90 , 91 ). Electrical brain activity (EEG) that could be recorded both in patients and animal models, is a useful tool for studying abnormalities in brain functioning.…”

Section: Sleep Disorders In Rett Syndrome and Rett-related Syndromementioning

confidence: 99%

“…Circadian clock in humans is found in a similar way in animals and locomotion's variation follow circadian rhythmicity ( 125 ). Thanks to the discovery of electrical brain activity, it was possible to investigate the sleep-wake cycle and using EEG technology, considered to be a neural biomarker and which can be recorded in animals and humans, translational research was made possible ( 90 ). As previously mentioned, sleep/wake cycle disorders are prevalent in RTT and MECP2, causative gene of the disease and highly expressed in the central circadian clock, suprachiasmatic nucleus (SCN) and photic stimulation leads to its phosphorylation ( 126 , 127 ).…”

Section: Sleep Disorders In Rett Syndrome and Rett-related Syndromementioning

confidence: 99%

“…Additionally, Liu et al reported that FOXG1 is implicated in the development of the epithalamus, which is involved in the stress response and sleep-wake cycle in vertebrates, consistent with the clinical pattern (emotional disorders, sleep problems and choroid cysts) expressed by patients suffering from FOXG1-related disorders ( 131 ). Zhang et al recently published a systematic review of sleep disturbances in RTT animal models, analyzing 13 studies in mutated models of Drosophila, cynomolgus monkeys and mouse, the latter the most used in current studies ( 90 ). Disruption in sleep continuity and efficacy are confirmed.…”

Section: Sleep Disorders In Rett Syndrome and Rett-related Syndromementioning

confidence: 99%

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Sleep Disorders in Rett Syndrome and Rett-Related Disorders: A Narrative Review

et al. 2022

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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.

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