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]

COMMENT. As the author concludes, the Rett syndrome concept is broader than previously believed and atypical variants must be recognized. Autopsy findings have been surprisingly limited even in advanced stages of the disease and have included moderate cortical atrophy and general brain shrinking with increasing age. Microscopically, there was mild gliosis without evidence of storage, underpigmentation in certain nigral structures, and axonal changes suggestive of degeneration in ascending and descending tracts.

Biochemical findings have included a reduction of brain noradrenaline, dopamine and seratonin, but no consistent abnormalities have been found. A genetic basis for Rett syndrome has been suggested but not satisfactorily confirmed.