Original article| Volume 23, SUPPLEMENT 1, S108-S112, December 2001

Clinical, neurophysiological and immunological correlations in classical Rett syndrome


      Rett syndrome (RTT) is neurodevelopmental disorder with the onset at critical period of postnatal ontogenesis and age dependent occurrence of clinical manifestations. The aim of the present study was to investigate possible correlations of the age of disease onset with clinical manifestations at the stage 3 of illness and neurobiological parameters. The study was carried out in 38 girls with classical RTT, aged from 3 to 7 years, and twenty and eighteen patients with the disease onset before and after the age of one year were divided into the groups 1 and 2 (Gr1 and Gr2), respectively. Quantitative EEG (QEEG) and measurement of the serum levels of autoantibodies (AAB) to nerve growth factor (NGF) were performed. Clinically, speech and motor functions were significantly more severely affected in the Gr1 than in the Gr2. In QEEG, spectral density of theta activity was significantly higher in Gr1 than in the Gr2. The titer of AAB to NGF was significantly increased in comparison with healthy controls, and the titer in Gr2 was higher than in Gr1.The data obtained suggests that patients with the classical RTT can be divided into subgroups according to the age of disease onset and genetic factors such as mosaicism of MeCP2 mutation may be associated with the heterogeneity of phenotype in RTT patients.


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        • Amir R.E.
        • Van den Veyver I.B.
        • Wan M.
        • Tran C.Q.
        • Francke U.
        • Zoghbi H.Y.
        Rett syndrome is caused by mutations in X-linked MECP2, encording methyl-CpG-binding protein 2.
        Nat Genet. 1999; 23: 185-188
        • Hagberg B.
        Rett syndrome: clinical peculiarities and biological mysteries.
        Acta Paediatr. 1995; 84: 971-976
        • Naidu S.
        Rett syndrome: natural history and underlying disease mechanisms.
        Eur Child Adolesc Psychiatry. 1997; 6: 14-17
        • Armstrong D.D.
        The neuropathology of the Rett syndrome.
        Brain Dev. 1992; 14: 89-98
        • Armstrong D.D.
        • Dunn J.K.
        • Antalffy B.
        • Trivedi R.
        Selective dendritic alterations in the cortex of Rett syndrome.
        J Neuropathol Exp Neurol. 1995; 54: 195-201
        • Belichenko P.V.
        • Hagberg B.
        • Dahlstrom A.
        Morphological studies of neocortical areas in Rett syndrome.
        Acta Neuropathol. 1997; 93: 50-61
        • Baumann M.L.
        • Kemper T.K.
        • Arin D.M.
        Pervasive neuroanatomic abnormalities of the brain in three cases of Rett's syndrome.
        Neurology. 1995; 45: 1581-1586
        • Segawa M.
        • Nomura Y.
        Polysomnography in the Rett syndrome.
        Brain Dev. 1992; 14: S46-S54
        • Kaufmann W.E.
        • Taylor C.V.
        • Hohmann C.F.
        • Sanwal I.B.
        • Naidu S.
        Abnormalities in neuronal maturation in Rett syndrome neocortex: preliminary molecular correlates.
        Eur Child Adolesc Psychiatry. 1997; 6: 75-77
        • Percy A.K.
        Neurobiology and neurochemistry of Rett syndrome.
        Eur Child Adolesc Psychiatry. 1997; 6: 80-82
        • Wenk G.L.
        • Mobley S.L.
        Choline acetyltransferase activity and vesamicol binding in Rett syndrome and in rats with nucleus basalis lesions.
        Neuroscience. 1996; 73: 79-84
        • Lappalainen R.
        • Lindholm D.
        • Riikonen R.
        Low levels of nerve growth factor in cerebrospinal fluid of children with Rett syndrome.
        J Child Neurol. 1996; 11: 296-300
        • Nomyra Y.
        • Segawa M.
        Clinical features of the early stage of the Rett syndrome.
        Brain Dev. 1990; 12: 16-19
        • Witt-Engerström I.
        Age-related occurrence or signs and symptoms in the Rett syndrome.
        Brain Dev. 1992; 14: S11-S20
        • Trevathan E.
        • Moser H.W.
        The Rett syndrome Diagnostic Criteria Work Group. Diagnostic criteria for Rett syndrome.
        Ann Neurol. 1988; 23: 425-428
        • Hagberg B.
        Condensed points for diagnostic and stages in Rett syndrome.
        Eur Child Adolesc Psychiatry. 1997; 6: 2-4
        • Vorsanova S.G.
        • Demidova I.A.
        • Ulas V.Yu.
        • Soloviev IV, K.r.
        • avets V.S.
        • Kazantseva L.Z.
        • Yurov Yu.B.
        Cytogenetic and molecular-cytogenetic investigations of Rett syndrome: report of 31 cases.
        Neuroreport. 1996; 8: 187-189
        • Harper G.P.
        • Glanville R.W.
        • Thoenen H.
        The purification of nerve growth factor from bovine seminal plasma.
        J Biol Chem. 1982; 25: 8541-8548
        • Niedermeyer E.
        • Naidu S.
        • Plate C.
        Unusual EEG theta rhythms over central region in Rett syndrome: considerations of the underlying dysfunction.
        Clin Electroencephalogr. 1997; 28: 36-43
        • Niedermeyer E.
        • Naidu S.B.
        Rett syndrome, EEG and the motor cortex as a model for better understanding of attention deficit hyperactivity disorder (ADHD).
        Eur Child Adolesc Psychiatry. 1998; 7: 69-72
        • Semenova L.K.
        • Vasilieva V.A.
        • Cehmistrenko T.A.
        Structural transformation of human neocortex in postnatal ontogenesis.
        in: Adrianov O.S. Farber D.A. Structural and functional organization of developing brain (in Russian). 1990: 8-44
        • Lipani J.D.
        • Bhattacharjee M.B.
        • Corey D.M.
        • Lee D.A.
        Reduced nerve growth factor in Rett syndrome postmortem brain tissue.
        J Neuropathol Exp Neurol. 2000; 59: 889-895
        • Crowley C.
        • Spencer S.D.
        • Nishimura M.C.
        • Chen K.S.
        • Pitts-Meek S.
        • Armanini M.P.
        • et al.
        Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons.
        Cell. 1994; 76: 1001-1011
        • Chen K.S.
        • Nishimura M.C.
        • Armanini M.P.
        • Crowley C.
        • Spencer S.D.
        • Phillips H.S.
        Disruption of a single allele of the nerve growth factor gene results in atrophy of basal forebrain cholinergic neurons and memory deficits.
        J Neurosci. 1997; 17: 7288-7296
        • Hohmann C.F.
        • Berger-Sweeney J.
        Cholinergic regulation of cortical development and plasticity. New twists to an old story.
        Perspect Dev Neurobiol. 1998; 5: 401-425
        • Berger-Sweeney J.
        The effects of neonatal basal forebrain lesions on cognition: towards understanding the developmental role of the cholinergic basal forebrain.
        Int J Dev Neurosci. 1998; 16: 603-612
        • Ricceri L.
        • Usiello A.
        • Valanzano A.
        • Calamandrei G.
        • Frick K.
        • Berger-Sweeney J.
        Neonatal 192 IgG-saporin lesions of basal forebrain cholinergic neurons selectively impair response to spatial novelty in adult rats.
        Behav Neurosci. 1999; 113: 1204-1215
        • Muir J.L.
        • Dunnett S.B.
        • Robbins T.W.
        • Everitt B.J.
        Attentional functions of the forebrain cholinergic systems: effects of intraventricular hemicholinium, physostigmine, basal forebrain lesions and intracortical grafts on a multiple-choice serial reaction time task.
        Exp Brain Res. 1992; 89: 611-622
        • Segawa M.
        Pathophysiology of Rett syndrome from the standpoint of early catecholeamin disturbance.
        Eur Child Adolesc Psychiatry. 1997; 6: 56-60
        • Strohmeier G.R.
        • Brunkhorst B.A.
        • Seetoo K.F.
        • Bernardo J.
        • Weil G.J.
        • Simons E.R.
        Neutrophil functional responses depend on immune complex valency.
        J Leukoc Biol. 1995; 56: 403-414
        • Trevani A.S.
        • Andonegui G.
        • Kempfer C.
        • Malchiodi E.
        • Geffner J.R.
        Activation of human neutrophils induced by immune complexes prepared with cationic and anionic fraction of normal antibodies.
        Scand J Immunol. 1996; 43: 341-344
        • Moser R.
        • Etter H.
        • Oliganti L.
        • Fehr J.
        Neutrophil activation in response to immune complex-bearing endothelial cells depends on the functional cooperation of Fc gamma RII (CD32) and Fc gamma RIII (CD16).
        J Lab Clin Med. 1995; 126: 588-596