Neurophysiology Versus Clinical Genetics in Rett Syndrome: A Multicenter Study

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 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc

La variante di Hanefeld e il Gene CDLK5

NODefinita come una patologici dello sviluppo neurologico che colpisce processi maturativi specifici delle cellule nervose, la sindrome di Rett (RTT) comporta la compromissione dello sviluppo cerebrale ed un conseguente grave deficit dell\u27organismo. L\u27eziologia della sindrome ? imputabile all\u27alterazione del gene MECP2 o di altri geni ad esso col lega li, localizzati nel cromosoma X. Ci? spiega l\u27insorgenza della malattia quasi esclusivamente nelle femmine con un \u27incidenza di 1:12000, manifestandosi dopo un primo anno di vita apparentemente normale. La lettura di questo volume - che individua le principali aree di ricerca nelle due sezioni "Clinica e natura della sindrome d? Reti" e "Terapia, comunicazione, integrazione sociale" - pu? servire a incoraggiare genitori, medici, insegnanti e terapisti del linguaggio e della motricit? nel conviincimento che intervenire con successo nei complessi risvolti clinici e sociali della RTT ? possibile, avendo cura di difendete le pazienti dalle pi? comuni complicanze neurologiche e ortopediche e aprendo un vano nel loro isolamento sociale e scolastico attraverso un adeguato e personalizzato intervento cognitivo e psicomotorio che favorisca la mobilit? e la comunicazion