Introduction Rett syndrome is a severe neurological disorder affecting predominantly females, characterized by the global deceleration of psychomotor development and the loss of acquired cognitive and motor skills, following an apparently normal or quasi-normal development during the first months of life [1, 2]. Rett syndrome is one of the most common causes of mental retardation in females, with an incidence of 1 in 10,000-15,000. The occurrence of stereotypic hand-washing activities and hand apraxia are among the more typical features of this condition which includes the failure to develop speech or the loss of all acquired speech during the so called regression phase. In fact the natural course of this disorder is depicted by a clinical staging system in four stages. Rett syndrome is recognized today to have a broader variability in clinical phenotype than originally thought, at the point of suggesting the concept of a Rett Complex [3], including the classical RS as well as different variants which occasionally may group together in large family trees [4]. It is likely that the more frequent variant is represented by the preserved speech variant (PSV) where the course of the disorder is more benign and the occurrence of associated abnormalities (microcephalus, scoliosis, epilepsy, etc.) more rare than in classic RS [5- 7]. Recently, mutations of the gene MECP2 (located at Xq28) have been identified in the majority of cases of sporadic classic Rett syndrome: this gene encodes the methyl-CpG-binding protein (MeCP2), which is critical for regulation of gene expression of an as yet unknown number and type of genes [8, 9]. De Bona et al. [10] have also shown that Rett PSV is allelic of classic Rett, Developmental profile of serum nerve growth factor levels in Rett complex Gemma CALAMANDREI (a), Luigi ALOE (b), Jousef HAJEK (c) and Michele ZAPPELLA (c) (a) Laboratorio di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanità, Rome, Italy (b) Istituto di Neurobiologia, Consiglio Nazionale delle Ricerche, Rome, Italy (c) Dipartimento di Neuropsichiatria Infantile, Azienda Ospedaliera Senese, Siena, Italy Summary. - Rett syndrome (RS) is a progressive neurodevelopmental disorder predominant in females, characterised by mental deficiency, stereotyped hand-washing and apraxia. Notwithstanding the recent identification of the MECP2 gene likely involved in the pathogenesis of SR, the neurobiological bases of this syndrome are still largely unknown. Converging evidence shows that the brain levels of nerve growth factor (NGF), a neurotrophin regulating the development and functioning of central cholinergic neurons, are decreased in RS girls. In this study, the serum levels of NGF were measured in classic RS, in the preserved speech variant (PSV) and in normal controls. Overall analysis failed to evidence significant differences among the three groups. However, whereas NGF levels increased significantly with age in controls, the opposite profile was observed in classic RS, with a progressive age-dependent decrease of NGF. In PSV subjects NGF levels remained constant with age. These findings strengthen the hypothesis of NGF involvement in the pathogenesis of RS. Key words: Rett syndrome, preserved speech variant (PSV), nerve growth factor, neurodevelopmental disorders. Riassunto (Profilo ontogenetico dei livelli sierici di nerve growth factor nella sindrome di Rett). - La sindro- me di Rett (SR) è un grave disordine neurologico a carattere progressivo che si manifesta nel sesso femminile entro il secondo anno di vita. Nonostante la recente identificazione del gene MECP2 verosimilmente coinvolto nella patogenesi della SR, le basi neurobiologiche della sindrome sono ancora sconosciute. Evidenze recenti indicano ridotti livelli di nerve growth factor (NGF), una neurotrofina che modula lo sviluppo e la funzione dei neuroni colinergici centrali, nel liquor e nella corteccia di soggetti Rett. In questo studio sono stati misurati i livelli di NGF nel siero di soggetti con SR (sia nella forma classica che in quella a linguaggio conservato) e in soggetti di controllo. I livelli complessivi di NGF non differivano significativamente tra i tre gruppi, ma contra- riamente a quanto osservato nei controlli, i livelli sierici di NGF diminuivano significativamente con l’età nella SR classica, e si mantenevano costanti nella variante a linguaggio conservato. Questi risultati rafforzano l’ipote- si di un coinvolgimento del NGF nella patogenesi della SR. Parole chiave: sindrome di Rett, variante a linguaggio conservato (PSV), nerve growth factor, disordini del neurosviluppo. Ann. Ist. Super. Sanità, vol. 37, n. 4 (2001), pp. 601-605