Rett syndrome: the Brazilian contribution to the gene discovery

ABSTRACT A brief history of the syndrome discovered by Andreas Rett is reported in this paper. Although having been described in 1966, the syndrome was only recognized by the international community after a report by Hagberg et al. in 1983. Soon, its importance was evident as a relatively frequent cause of severe encephalopathy among girls. From the beginning it was difficult to explain the absence of male patients and the almost total predominance of sporadic cases (99%), with very few familial cases. For these reasons, it was particularly difficult to investigate this condition until 1997, when a particular Brazilian family greatly helped in the final discovery of the gene, and in the clarification of its genetic mechanism. Brief references are made to the importance of the MECP2 gene, 18 years later, as well as to its role in synaptogenesis and future prospects.

Rett Syndrome

Rett Syndrome (RTT) is a neurodevelopmental disorder that predominantly affects females but males with RTT have been identified. RTT was first described by an Austrian pediatrician, Andreas Rett. Rett syndrome was mapped to chromosome Xq28 in 1998 and a year later it was determined to be due to mutations in the MeCP2 gene at this locus. Identification of the gene led to the broadening of the clinical phenotype and further characterization into classic and atypical forms of the disease that overlap with Autism spectrum disorders during the period of regression. More than 95% of individuals with classic RTT have mutations in the MeCP2 gene.

Síndrome de Rett. Descripción de dos casos

El Síndrome de Rett (SR) fue descrito inicialmente en 1966 por Andreas Rett. Comprende una involución mental progresiva de inicio antes de los dos años acompañada de pérdida de contacto social y movimientos estereotipados de las manos, apraxia /ataxia de la marcha y crisis de hiperventilación, presentándose exclusivamente en mujeres (1).

The History and Challenge of Rett Syndrome

Rett syndrome was first described in 1966 by Dr Andreas Rett, who reported in German his findings in 22 patients. Recognition of the syndrome grew slowly until 1983, when a series of 35 patients from several countries was reported in English. By 1987, the number of known cases had grown to over 1,250 worldwide, the International Rett Syndrome Association had been founded, and international conferences on the syndrome were being held regularly. Although a developmental staging system has been devised, many questions remain concerning the course of the disease. Rett syndrome poses a challenge to the physicians, therapists, psychologists, educators, and families involved with affected patients, as well as to researchers investigating the syndrome. (J Child Neurol 1988;3(Suppl):S3-S5).