Rett syndrome: An update

BACKGROUND- Rett syndrome (RS) is a neurologic disorder that primarily affects girls. A genetic marker has recently been identified. Although RS is associated with a devastating loss of function between infancy and the fifth year of life, its course is relatively static thereafter, setting it apart from most neurodegenerative and genetic disorders of childhood. Clinical, neuropathological, and neurochemical studies call attention to RS as a neurodevelopmental disorder. REVIEW SUMMARY- Rett syndrome is a distinct clinical entity, with a unique cluster of clinical signs and symptoms observed in a large number of girls in all ethnic groups. RS affects early development first with stagnation (stage 1), then with devastating cognitive and motor regression (stage 2), partial recovery (stage 3), and cognitive stability (stage 4). Epidemiologic studies have supported the hypothesis that RS is genetically determined. After years of research, it is now known that RS is caused by mutations in the methyl-CpG-binding protein-2 gene on chromosome Xq28. Neuropathological studies point to developmental. abnormalities dating back to the late second or third trimester in utero. However, the major impact of the disease occurs during postnatal brain growth, involving synapse formation. Alterations in the dopaminergic, cholinergic, and glutaminergic neurotransmitters play an important role in growing nerve processes and morphogenesis in the developing nervous system. CONCLUSIONS- The identification of a biological marker, combined with improved understanding of the pathogenetic mechanisms, provide hope for therapeutic intervention sufficiently early to alter the course of irreversible brain damage.