We report 5 girls presenting Rett syndrome. All of them were from south Tunisi They fulfilled the Rett syndrome diagnosis criteria (The Rett syndrome diagnosis criteria work group, 1988). Pregnancy, birth and psychomotor development during the first year of live were normal. The mean age at the onset was 19.8 +/- 2.5 months. The two revealing symptoms were psychomotor regression (3 cases) and epilepsy (2 cases). They were admitted to our ward at a mean age of 4.7 +/- 1.5 years. Clinical presentation was typical of Rett syndrome. Mental retardation, stereotypic hand movement (hand washing/wringing or clapping/tapping) and loss of purposeful manual skills were noted in all cases. Gait was apraxic and increase of head circumference was slowed. Additional features included, respiratory dysfunction (episodic hyperventilation and breath-holding), epilepsy, scoliosis (4 cases), growth retardation and spasticity (3 cases). Electroencephalography showed slow activity with multifocal epileptiform abnormalities. Sleep enhanced these EEG abnormalities. MRI and CT-scan disclosed non specific cortical and sub-cortical atrophy. All cases were isolated and parents were consanguineous in 3 cases. Rett syndrome is relatively frequent in Europe, but in Tunisia this disease remains rare and certainly underdiagnosed.