Long-Term Follow-Up of Rett Syndrome

Rett syndrome is a neurodevelopmental disorder that occurs worldwide and predominantly affects girls. The MECP2 gene has been put forward as the underlying gene. Interestingly, other clinical presentations in addition to Rett syndrome have been reported to be the results of deviations in MECP2. This prompted us to outline a working hypothesis of how these diverse phenotypes are connected. Our aim was to summarize the clinical picture of deviations in MECP2 at this moment to obtain a comprehensive overview. Thus, we have attempted to create a gradient, starting at the left with the most severely affected MECP2-deviant subgroups, represented by boys who are diseased in the intrauterine phase or as neonates, and at the right, the most mildly affected subgroup, female asymptomatic carriers. In the center, with dominant numbers, we 728 Journal of Child Neurology / Volume 20, Number 9, September 2005 Rett syndrome is a condition with a strict clinical definition.1,2 In contrast, MECP2 mutations result in a broad spectrum of phenotypes,3 of which Rett syndrome is merely one example. In our experience, this distinction is important. Girls affected by Rett syndrome display a wide variety of somewhat peculiar and easily missed developmental deficiencies, early delineation of which is essential to ensure the correct understanding, genetic counseling, and adequate implementation of different habilitation efforts. Here we present a provisional working concept to illustrate the range of MECP2-deviant phenotypes (Figure 1) within this field, which is rapidly expanding as our understanding of the underlying biology of these conditions continues to grow and, in turn, influence patient care. This report contributes to the ongoing discussion regarding MECP2 phenotypes versus the clinical diagnosis of Rett syndrome. Our focus is not to include all known MECP2 mutations but to summarize the current clinical picture of deviations in MECP2 and offer a comprehensive overview. This information will be useful for clinicians and families who seek an explanation and a name for the complex disability affecting their child.