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Clinical and genetic Rett syndrome variants are defined by stable electrophysiological profiles
BACKGROUND: Rett Syndrome (RTT) is a complex neurodevelopmental disorder, frequently associated with epilepsy. Despite increasing recognition of the clinical heterogeneity of RTT and its variants (e.g Classical, Hanefeld and PSV(Preserved Speech Variant)), the link between causative mutations and ob...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195747/ https://www.ncbi.nlm.nih.gov/pubmed/30340473 http://dx.doi.org/10.1186/s12887-018-1304-7 |
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author | Keogh, Conor Pini, Giorgio Dyer, Adam H. Bigoni, Stefania DiMarco, Pietro Gemo, Ilaria Reilly, Richard Tropea, Daniela |
author_facet | Keogh, Conor Pini, Giorgio Dyer, Adam H. Bigoni, Stefania DiMarco, Pietro Gemo, Ilaria Reilly, Richard Tropea, Daniela |
author_sort | Keogh, Conor |
collection | PubMed |
description | BACKGROUND: Rett Syndrome (RTT) is a complex neurodevelopmental disorder, frequently associated with epilepsy. Despite increasing recognition of the clinical heterogeneity of RTT and its variants (e.g Classical, Hanefeld and PSV(Preserved Speech Variant)), the link between causative mutations and observed clinical phenotypes remains unclear. Quantitative analysis of electroencephalogram (EEG) recordings may further elucidate important differences between the different clinical and genetic forms of RTT. METHODS: Using a large cohort (n = 42) of RTT patients, we analysed the electrophysiological profiles of RTT variants (genetic and clinical) in addition to epilepsy status (no epilepsy/treatment-responsive epilepsy/treatment-resistant epilepsy). The distribution of spectral power and inter-electrode coherence measures were derived from continuous resting-state EEG recordings. RESULTS: RTT genetic variants (MeCP2/CDLK5) were characterised by significant differences in network architecture on comparing first principal components of inter-electrode coherence across all frequency bands (p < 0.0001). Greater coherence in occipital and temporal pairs were seen in MeCP2 vs CDLK5 variants, the main drivers in between group differences. Similarly, clinical phenotypes (Classical RTT/Hanefeld/PSV) demonstrated significant differences in network architecture (p < 0.0001). Right tempero-parietal connectivity was found to differ between groups (p = 0.04), with greatest coherence in the Classical RTT phenotype. PSV demonstrated a significant difference in left-sided parieto-occipital coherence (p = 0.026). Whilst overall power decreased over time, there were no difference in asymmetry and inter-electrode coherence profiles over time. There was a significant difference in asymmetry in the overall power spectra between epilepsy groups (p = 0.04) in addition to occipital asymmetry across all frequency bands. Significant differences in network architecture were also seen across epilepsy groups (p = 0.044). CONCLUSIONS: Genetic and clinical variants of RTT are characterised by discrete patterns of inter-electrode coherence and network architecture which remain stable over time. Further, hemispheric distribution of spectral power and measures of network dysfunction are associated with epilepsy status and treatment responsiveness. These findings support the role of discrete EEG profiles as non-invasive biomarkers in RTT and its genetic/clinical variants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12887-018-1304-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6195747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-61957472018-10-30 Clinical and genetic Rett syndrome variants are defined by stable electrophysiological profiles Keogh, Conor Pini, Giorgio Dyer, Adam H. Bigoni, Stefania DiMarco, Pietro Gemo, Ilaria Reilly, Richard Tropea, Daniela BMC Pediatr Research Article BACKGROUND: Rett Syndrome (RTT) is a complex neurodevelopmental disorder, frequently associated with epilepsy. Despite increasing recognition of the clinical heterogeneity of RTT and its variants (e.g Classical, Hanefeld and PSV(Preserved Speech Variant)), the link between causative mutations and observed clinical phenotypes remains unclear. Quantitative analysis of electroencephalogram (EEG) recordings may further elucidate important differences between the different clinical and genetic forms of RTT. METHODS: Using a large cohort (n = 42) of RTT patients, we analysed the electrophysiological profiles of RTT variants (genetic and clinical) in addition to epilepsy status (no epilepsy/treatment-responsive epilepsy/treatment-resistant epilepsy). The distribution of spectral power and inter-electrode coherence measures were derived from continuous resting-state EEG recordings. RESULTS: RTT genetic variants (MeCP2/CDLK5) were characterised by significant differences in network architecture on comparing first principal components of inter-electrode coherence across all frequency bands (p < 0.0001). Greater coherence in occipital and temporal pairs were seen in MeCP2 vs CDLK5 variants, the main drivers in between group differences. Similarly, clinical phenotypes (Classical RTT/Hanefeld/PSV) demonstrated significant differences in network architecture (p < 0.0001). Right tempero-parietal connectivity was found to differ between groups (p = 0.04), with greatest coherence in the Classical RTT phenotype. PSV demonstrated a significant difference in left-sided parieto-occipital coherence (p = 0.026). Whilst overall power decreased over time, there were no difference in asymmetry and inter-electrode coherence profiles over time. There was a significant difference in asymmetry in the overall power spectra between epilepsy groups (p = 0.04) in addition to occipital asymmetry across all frequency bands. Significant differences in network architecture were also seen across epilepsy groups (p = 0.044). CONCLUSIONS: Genetic and clinical variants of RTT are characterised by discrete patterns of inter-electrode coherence and network architecture which remain stable over time. Further, hemispheric distribution of spectral power and measures of network dysfunction are associated with epilepsy status and treatment responsiveness. These findings support the role of discrete EEG profiles as non-invasive biomarkers in RTT and its genetic/clinical variants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12887-018-1304-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-19 /pmc/articles/PMC6195747/ /pubmed/30340473 http://dx.doi.org/10.1186/s12887-018-1304-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Keogh, Conor Pini, Giorgio Dyer, Adam H. Bigoni, Stefania DiMarco, Pietro Gemo, Ilaria Reilly, Richard Tropea, Daniela Clinical and genetic Rett syndrome variants are defined by stable electrophysiological profiles |
title | Clinical and genetic Rett syndrome variants are defined by stable electrophysiological profiles |
title_full | Clinical and genetic Rett syndrome variants are defined by stable electrophysiological profiles |
title_fullStr | Clinical and genetic Rett syndrome variants are defined by stable electrophysiological profiles |
title_full_unstemmed | Clinical and genetic Rett syndrome variants are defined by stable electrophysiological profiles |
title_short | Clinical and genetic Rett syndrome variants are defined by stable electrophysiological profiles |
title_sort | clinical and genetic rett syndrome variants are defined by stable electrophysiological profiles |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195747/ https://www.ncbi.nlm.nih.gov/pubmed/30340473 http://dx.doi.org/10.1186/s12887-018-1304-7 |
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