[Rett syndrome: 50 years' history of a still not well known condition]

Abstract

Since it was first described by Andrea Rett 50 years ago, Rett syndrome (RS) has been the subject of further investigations, nonetheless it continues to be a not well known condition. Our own experience and an updated literature review on RS is presented. RS is a severe dominant X chromosome-linked neurodevelopmental disorder with a characteristic clinical picture that mostly occurs in girls, most of the cases are sporadic and genetically determined. The diagnosis of RS is made based on observation and clinical assessment. Main clinical features are mental retardation, behavioural changes, stereotypes, loss of speech and hand skills, gait apraxia, irregular breathing with hyperventilation while awake, and frequent seizures. The internationally established criteria are reviewed. RS is caused by mutations in MECP2 in the majority of cases, but a proportion of atypical cases may result from mutations in CDKL5, particularly the early onset seizure variant. However, the molecular pathogenesis of this disorder remains unclear, as well as the relation between the mutations in MECP2 and other neurodevelopmental disorders. Neuroimaging, neuropathological and biochemical findings in RS are reviewed. Besides symptomatic treatment, no therapeutic trials have shown effectiveness. Some perspectives in the treatment of RS have been provided by a recent work showing a phenotypic reversal by activation of MeCP2 expression in a mouse model.