Téma: Review papers

Rett syndrome: history, clinical features and atypical variants

Vladimír Bzdúch1, Katarína Jariabková2, Miriam Kolníková3

Rett syndrome is a X-linked progressive childhood neurodevelopmental disorder that primarily affects females. The incidence is 1 : 10 000 – 15 000 females worldwide, making it one of the major causes of severe mental retardation in females. The clinical characteristics of this syndrome were first reported in the German literature in 1966 by Austrian pediatrician Andreas Rett. Almost 20 years have passed since Rett syndrome became internationally accepted as a unique disorder. The association of Rett syndrome with mutations in the methyl-CpG binding protein 2 gene (MECP2) was recognised in 1999 by Huda Zoghbi. Clinically it can be classified into classic and atypical phenotype. Classic Rett syndrome is characterized by normal development from birth until 6 months of age, followed by regression with loss of acquired skills and speech and development, stereotypic hand movements and frequently development of microcephaly. Several atypical Rett variants have been described that include the congenital variant, the early onset seizure variant, the forme fruste with the late onset of symptoms, the late regression variant, and the variant with spared communication skills. MECP2 gene alterations are present only in 50-70 % atypical cases. Mutations in other genes, most often CDKL5 and FOXG1 have been discovered and associated with atypical Rett variants mostly with early onset seizures and congenital form.