title: Neurophysiology versus clinical genetics in Rett syndrome: A multicenter study.
abstract: Many studies have attempted to establish the genotype-phenotype correlation in Rett syndrome (RTT). Cardiorespiratory measurements provide robust objective data, to correlate with each of the different clinical phenotypes. It has important implications for the management and treatment of this syndrome. The aim of this study was to correlate the genotype with the quantitative cardiorespiratory data obtained by neurophysiological measurement combined with a clinical severity score. This international multicenter study was conducted in four European countries from 1999 to 2012. The study cohort consisted of a group of 132 well-defined RTT females aged between 2 and 43 years with extended clinical, molecular, and neurophysiological assessments. Diagnosis of RTT was based on the consensus criteria for RTT and molecular confirmation. Genotype-phenotype analyses of clinical features and cardiorespiratory data were performed after grouping mutations by the same type and localization or having the same putative biological effect on the MeCP2 protein, and subsequently on eight single recurrent mutations. A less severe phenotype was seen in females with CTS, p.R133C, and p.R294X mutations. Autonomic disturbances were present in all females, and not restricted to nor influenced by one specific group or any single recurrent mutation. The objective information from non-invasive neurophysiological evaluation of the disturbed central autonomic control is of great importance in helping to organize the lifelong care for females with RTT. Further research is needed to provide insights into the pathogenesis of autonomic dysfunction, and to develop evidence-based management in RTT. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Netherlands Rett Expertise Center-GKC, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Nicky
authors.initials: N
authors.lastname: Halbach
authors.affiliation: Netherlands Rett Expertise Center-GKC, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Smeets
authors.affiliation: Neurodegeneration and Neuroinflamation, Imperial College London, London, United Kingdom.|The National Swedish Rett Center, Frösön, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Julu
authors.affiliation: The National Swedish Rett Center, Frösön, Sweden.
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Witt-Engerström
authors.affiliation: Tuscany Rett Center, Versilia Hospital, Camaiore (Lucca), Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pini
authors.affiliation: Medical Genetic Unit, Ferrara University Hospital, Ferrara, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bigoni
authors.affiliation: Institute of Neurological Sciences, Southern General Hospital, NHS Greater, Glasgow and Clyde, Ferrara, United Kingdom.
authors.forename: Stig
authors.initials: S
authors.lastname: Hansen
authors.affiliation: Institute of Neurological Sciences, Southern General Hospital, NHS Greater, Glasgow and Clyde, Ferrara, United Kingdom.
authors.forename: Flora
authors.initials: F
authors.lastname: Apartopoulos
authors.affiliation: Regional Neuroscience Center, King's College Hospital NHS Foundation Trust and King's College London, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Delamont
authors.affiliation: Clinical Genomics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Kees
authors.initials: K
authors.lastname: van Roozendaal
authors.affiliation: Tuscany Rett Center, Versilia Hospital, Camaiore (Lucca), Italy.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Scusa
authors.affiliation: Division of Neurology, Versilia Hospital, Camaiore (Lucca), Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Borelli
authors.affiliation: Department of Methodology and Statistics, School for Public Health and Primary Care CAPHRI, Maastricht University, Maastricht, The Netherlands.
authors.forename: Math
authors.initials: M
authors.lastname: Candel
authors.affiliation: Netherlands Rett Expertise Center-GKC, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Leopold
authors.initials: L
authors.lastname: Curfs
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D009483:Neuropsychological Tests; D010641:Phenotype; D015518:Rett Syndrome / Q000175:diagnosis* / Q000235:genetics*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D051783:Methyl-CpG-Binding Protein 2
keywords: MECP2; Rett syndrome; neurophysiology