Sleep problems in individuals with Rett Syndrome: A systematic review and meta-analysis

Importance

Prognosis and understanding of sleep disorders in rare genetic syndromes is limited, despite being a common complaint of caregivers. Rett Syndrome (RTT) is a rare, progressive neurodevelopmental disorder with problematic sleeping being a clinical feature yet inconsistencies exist in the literature.

Objective

To examine the strength of evidence of a sleep disorder in RTT. To investigate the complaints reported based on a sleep disorders classification approach and to determine differences in rates per the RTT main clinical features.

Data sources

PubMed, Web of Science, PsycINFO, Ebsco, Scopus, and Cochrane Library up to November 4^th 2021 with no time or language limitation (CRD 42020198099) were searched.

Study selection

Original research published in peer-reviewed journals, with RTT clinical or genetic diagnosis reported and stating a sleep complaint with prevalence rate, were selected.

Data Extraction and Synthesis

We followed the PRISMA guideline for abstracting data and assessed risk of bias with the NIH quality assessment tools. The prevalence rates were meta-analyzed applying the mixed-effects model with measures of consistency.

Main Outcome(s) and Measure(s)

The International Classification of Sleep Disorders was used to summarize sleep complaints reported in the literature. Those that did not specify the precise sleep complaint were categorized as a not otherwise specified sleep problem. We further analyzed data per available RTT characteristics.

Results

We included 19 studies (n = 4298, 0.3 to 57.2 years old) across five countries involving predominantly observational study designs. Overall, 54.1% (95%CI: 43.8% to 64.5%) of individuals with RTT exhibit problematic sleeping, in particular, excessive somnolence (67.5%; 95%CI: 47.5% to 82.7%) and difficulties initiating and maintaining sleep (61%; 95%CI: 49.6% to 71.4%). Disturbed sleep not otherwise specified was reported in 57.1% (95%CI: 34.5% to 81.3%). Although studies could improve details reported, females with MECP2-RTT showed a higher prevalence rate of excessive somnolence and sleep-wake transition disorders than those diagnosed by CDKL5-RTT. Prevalence rates remain roughly unaltered across the lifespan. Sleep disorders are about two times more prevalent than in typically developing children.

Conclusions and Relevance

Findings indicate predominantly disorders regarding maintenance of sleep and wake state, which persist throughout their lifespan. Improved reporting of clinical features in cases with RTT phenotypes and of sleep behavior frequency and severity may lead to explicit prevalence rates. This is fundamental to progress in the pathophysiological investigation of altered sleep-wake mechanisms and to implement tailored sleep interventions for individuals with RTT, and families.