The clinical peculiarities and differential diagnosis of Rett syndrome are reviewed from the Department of Pediatrics Children's Clinics, East Hospital, Goteborg, Sweden. The four clinical stages of classic Rett syndrome are as follows. 1) Early onset stagnation, 2) rapid developmental regression, 3) pseudostationary period, 4) late motor deterioration. A variety of atypical variants have been described including some in boys. The development during the first few months of life is sometimes abnormal, rarely there is no subsequent deterioration phase, and occasionally seizures occur early as infantile spasms. The term “formes frustes” has been coined for these abortive variants. The differential diagnosis in Rett syndrome stage 2, which includes rapid developmental regression, increased irritability, screaming episodes and loss of acquired skills, is as follows: Infantile neuronal ceroid lipofuscinosis, encephalitis, toxic encephalopathies, epileptic encephalopathies, infantile autism, neurocutaneous syndromes, glutaric aciduria, amino acidopathy, and ataxic cerebral palsy. Biologic markers and effective screening procedures for an early diagnosis are lacking. A possible viral origin with a disorder similar to SSPE is now being suggested as an etiology of this syndrome. [1]