Rett syndrome is a neurodevelopmental disorder which is seen almost exclusively in females. It is caused by mutations in the X-linked gene MECP2 (methyl-CpG-binding protein 2). The disease is characterized by loss of communication with cognitive, verbal, fine and gross motor abilities following a normal early development. Rett syndrome is a clinical diagnosis, however, molecular testing is supportive. This review presents an overview of the clinical features of Rett syndrome and also major principles for clinical approach. Diagnostic criteria of Rett syndrome, typical and atypical forms of the disease and differential diagnosis are also summarized. Increasing awareness of pediatricians on Rett syndrome would enable earlier diagnoses and more appropriate therapeutic approaches. These in turn would prevent unnecessary diagnostic investigations and provide the families with more realistic information on treatment options and recurrence risks.

Keywords: Rett syndrome, MECP2 mutation