Neuropsychiatric Aspects of Fragile X Syndrome

Fragile X Syndrome (FXS) is an important cause of both mental retardation and neuropsychiatric disorders, producing its effects by a novel genetic mechanism. Complexities of interacting variables: intelligence quotient (IQ), subject age, limitations of neuropsychiatric testing modalities on the one hand, and the complex genetic mechanism on the other, render exact correspondences between genetic, neural, and neuropsychiatric variables problematic. Nevertheless, current research trends show a convergence of genetic, embryologic, neurocognitive, and neurobehavioral studies on an understanding of pathogenesis centered on the protein product of FMR1, FMRP, with a spectrum of neurocognitive and neuropsychiatric dysfunctions and deficits in turn depending upon tissue mosaicism and other factors determining FMRP production in critical tissues. The resulting neurobehavioral phenotype includes deficits in short-term memory, sequential information processing and visual/spatial abilities, pragmatic language abnormalities, dysfunctional social behavior with peers (gaze-avoidance, aloofness), unusual responses to sensory stimuli, and stereotypy. The proposed psychiatric phenotype now includes attention-deficit hpyeractivity disorder (ADHD), avoidant disorder, pervasive developmental disorders, anziety disorders, mood disorders, and schizotypal personality disorder.