Rett Syndrome: From Bed to Bench

Rett syndrome (RTT), a neurodevelopmental condition characterized by delayed-onset loss of spoken language and the development of distinctive hand stereotypies, affects approximately 1 in 10,000 live female births. Clinical diagnosis has been based on symptoms such as loss of acquired purposeful han...

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Main Authors: Shih-Ming Weng, Mark E.S. Bailey, Stuart R. Cobb
Format: Article
Language:English
Published: Elsevier 2011-12-01
Series:Pediatrics and Neonatology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1875957211001185
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author Shih-Ming Weng
Mark E.S. Bailey
Stuart R. Cobb
author_facet Shih-Ming Weng
Mark E.S. Bailey
Stuart R. Cobb
author_sort Shih-Ming Weng
collection DOAJ
description Rett syndrome (RTT), a neurodevelopmental condition characterized by delayed-onset loss of spoken language and the development of distinctive hand stereotypies, affects approximately 1 in 10,000 live female births. Clinical diagnosis has been based on symptoms such as loss of acquired purposeful hand skills, autistic behaviors, motor dysfunctions, seizure disorders, and gait abnormalities. RTT is a genetic disease and is caused almost exclusively by mutations in the X-linked gene, MECP2, to produce a phenotype that is thought to be primarily of neurological origin. Clinical reports show RTT patients to have a smaller brain volume, especially in the cerebral hemispheres, and alterations in various neurotransmitter systems, including acetylcholine, dopamine, serotonin, glutamate, substance P, and various trophic factors. Because of its monogenetic characteristic, disruption of Mecp2 is readily recapitulated in mice to produce a prominent RTT-like phenotype and provide an excellent platform for understanding the pathogenesis of RTT. As shown in human studies, Mecp2 mutants also display subtle alterations in neuronal morphology, including smaller cortical neurons with a higher-packing density and reduced dendritic complexity. Neurophysiological studies in Mecp2-mutant mice consistently report alterations in synaptic function, notably, defects in synaptic plasticity. These data suggest that RTT might be regarded as a synaptopathy (disease of the synapse) and thus potentially amenable to rational therapeutic intervention.
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spelling doaj-art-720636e9e15e4a4088c4d3379b54eb3d2025-08-20T02:15:54ZengElsevierPediatrics and Neonatology1875-95722011-12-0152630931610.1016/j.pedneo.2011.08.002Rett Syndrome: From Bed to BenchShih-Ming Weng0Mark E.S. Bailey1Stuart R. Cobb2Institute for Neuroscience and Psychology, University of Glasgow, Glasgow, United KingdomSchool of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United KingdomInstitute for Neuroscience and Psychology, University of Glasgow, Glasgow, United KingdomRett syndrome (RTT), a neurodevelopmental condition characterized by delayed-onset loss of spoken language and the development of distinctive hand stereotypies, affects approximately 1 in 10,000 live female births. Clinical diagnosis has been based on symptoms such as loss of acquired purposeful hand skills, autistic behaviors, motor dysfunctions, seizure disorders, and gait abnormalities. RTT is a genetic disease and is caused almost exclusively by mutations in the X-linked gene, MECP2, to produce a phenotype that is thought to be primarily of neurological origin. Clinical reports show RTT patients to have a smaller brain volume, especially in the cerebral hemispheres, and alterations in various neurotransmitter systems, including acetylcholine, dopamine, serotonin, glutamate, substance P, and various trophic factors. Because of its monogenetic characteristic, disruption of Mecp2 is readily recapitulated in mice to produce a prominent RTT-like phenotype and provide an excellent platform for understanding the pathogenesis of RTT. As shown in human studies, Mecp2 mutants also display subtle alterations in neuronal morphology, including smaller cortical neurons with a higher-packing density and reduced dendritic complexity. Neurophysiological studies in Mecp2-mutant mice consistently report alterations in synaptic function, notably, defects in synaptic plasticity. These data suggest that RTT might be regarded as a synaptopathy (disease of the synapse) and thus potentially amenable to rational therapeutic intervention.http://www.sciencedirect.com/science/article/pii/S1875957211001185animal modelMECP2Rett Syndrome
spellingShingle Shih-Ming Weng
Mark E.S. Bailey
Stuart R. Cobb
Rett Syndrome: From Bed to Bench
Pediatrics and Neonatology
animal model
MECP2
Rett Syndrome
title Rett Syndrome: From Bed to Bench
title_full Rett Syndrome: From Bed to Bench
title_fullStr Rett Syndrome: From Bed to Bench
title_full_unstemmed Rett Syndrome: From Bed to Bench
title_short Rett Syndrome: From Bed to Bench
title_sort rett syndrome from bed to bench
topic animal model
MECP2
Rett Syndrome
url http://www.sciencedirect.com/science/article/pii/S1875957211001185
work_keys_str_mv AT shihmingweng rettsyndromefrombedtobench
AT markesbailey rettsyndromefrombedtobench
AT stuartrcobb rettsyndromefrombedtobench