Rett's SyndromeDESCRIPTION
Rett's syndrome (RS) is a neurodevelopmental disorder of infancy almost exclusively affecting females. RS is characterized by severe regression of cognitive, motor, language, and social abilities between the age of 4 and 18 months, following a seemingly normal period of development. Hallmark features include stereotypic hand movements (hand wringing), microencephaly, and autistic-like behaviors. Prevalence ranges from 1:10,000 to 1:22,000 with diverse representation among the world population. The syndrome is named after Andreas Rett who, in 1966, first described its clinical features.
NEUROPATHOLOGY/PATHOPHYSIOLOGY
RS is a genetic disorder caused by mutation on the X-linked MECP2 gene, and subsequent MeCP2 protein deficiency (Amir et al., 1999; Hagberg, 2002). The majority of cases occur sporadically; inherited cases are rare. Genotype–phenotype studies have identified different clinical abnormalities associated with different MECP2 mutations (Percy, 2008a; Zhang & Minassian, 2008).
Studies to determine the specific neuropathology/neurophysiology of RS have found decelerated head growth starting at 3–6 months leading to microencephaly, decreased size of the dendrites of pyramidal neurons in the frontal and temporal lobes, and abnormalities in the substantia nigra. Neuropathology also involves the precentral gyrus, frontal cortex, superior temporal area, and parietal cortex (Brodmann areas 4, 45, 22 and 40). MRI findings have revealed atrophy in selective regions of gray and white matter in the prefrontal, frontal, and anterior temporal regions (Ibrahim & Khan, 2008; Pizzamiglio et al., 2008). EEG findings are characterized by the appearance of focal, multifocal, and generalized epileptiform abnormalities and the occurrence of theta activity in the frontal-central regions. Frequent seizure activity is reported; however, video EEG monitoring is critical because many apparent seizures are not correlated with EEG activity (Glaze, 2002).