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Meta-Analysis
. 2023 Jan 16;12(1):5.
doi: 10.1186/s13643-023-02169-6.

Global prevalence of Rett syndrome: systematic review and meta-analysis

Uarda Petriti  1 , Daniel C Dudman  2   3 , Emil Scosyrev  4 , Sandra Lopez-Leon  5   6
Affiliations
Meta-Analysis

Global prevalence of Rett syndrome: systematic review and meta-analysis

Uarda Petriti et al. Syst Rev. .

Abstract

Background: Rett syndrome is a rare, severe neurodevelopmental disorder. Almost all cases occur in girls, in association with spontaneous (non-inherited) mutations involving the methyl-CpG-binding protein 2 gene located on the X chromosome. Diagnostic criteria for typical Rett syndrome require a period of regression, followed by recovery or stabilization, and fulfillment of all four main criteria (loss of purposeful hand skills, loss of spoken language, gait abnormalities, and stereotypic hand movements). Our objective was to estimate the prevalence of Rett syndrome in the general population, stratified by sex.

Methods: We conducted a search of PubMed, Embase, Web of Science, Cochrane Library, LILACS, and LIVIVO to retrieve studies published in English between Jan. 1, 2000, and June 30, 2021. Pooled prevalence with a 95% confidence interval (CI) was estimated using a random-effects meta-analysis based on a generalized linear mixed model with a logit link.

Results: Ten eligible studies were identified (all in females), with a combined sample size of 9.57 million women and 673 Rett syndrome cases. The pooled prevalence estimate (random effects) was 7.1 per 100,000 females (95% CI: 4.8, 10.5, heterogeneity p < 0.001). Despite greatly variable precision of estimation, all estimates were compatible with a prevalence range of approximately 5 to 10 cases per 100,000 females based on their respective 95% CIs.

Conclusion: These findings may facilitate planning of therapeutic trials in this indication in terms of target sample size and accrual times.

Keywords: Epidemiology; Incidence; MECP2; Meta-analysis; Neurodevelopmental disorders; Prevalence; Rare diseases; Rett syndrome (RTT); Systematic literature review.

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Conflict of interest statement

SLL and ES are employees of Novartis Pharmaceutical Company; the statements presented in the paper do not necessarily represent the position of the company. UP is an employee of Cognizant Technology Solutions working on behalf of Novartis; the statements presented in the paper do not necessarily represent the position of either company. DCD is a former employee of Novartis Pharmaceutical Company and a former employee of Rutgers University Ernest Mario School of Pharmacy. DCD is a current employee of Seqirus.

Figures

Fig. 1
Fig. 1
PRISMA 2020 flow diagram for new systematic reviews. Searches of databases and registers only were included. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Fig. 2
Fig. 2
Forest plot demonstrating the study-specific prevalence of Rett syndrome estimates per 100,000 females (95% confidence interval)
Fig. 3
Fig. 3
Funnel plot demonstrating the estimated prevalence of Rett syndrome compared with margin of error (half-length of the 95% confidence interval) to examine the variability of the study-specific estimates as a function of their estimated precision
See this image and copyright information in PMC

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