Advances in research on the fragile X syndrome

Fragile X syndrome is a neurodevelopmental disorder that results from a sin gle gene mutation on the X chromosome. The purpose of this review is to sum marize key advances made in understanding the fragile X premutation gene se en in carriers and the full mutation gene seen in persons with the syndrome . DNA testing has replaced cytogenetic testing as the primary method for id entification of fragile X, although the efficacy of protein level screening is being explored. The premutation is associated with no effects, although there is evidence of physical effects-primarily premature menopause and mi ld outward features of the fragile X syndrome-among premutation carriers. T here is much controversy regarding premutation effects on psychological dev elopment. The few experimental studies carried out to date do not suggest n oticeable or significant effects. One challenge in addressing this controve rsy is the sometimes ambiguous differentiation between premutation and full mutation genes. There is a well-established yet highly variable phenotype of the full mutation. Research from this decade has helped to address speci fic aspects of this phenotype, including the early course of its developmen t in males, the influence of home and family environments, the nature of so cial difficulties and autistic features seen in boys and girls with fragile X, and the potential role of hyperarousal or hyper-reactivity. Studies in these areas, and on the role of FMR protein, will contribute towards ongoin g advances in our understanding of fragile X syndrome and its mechanisms. T he variability in physical, social, and cognitive features, as described in this review, is one that prohibits clear-cut screening guidelines designed to avoid high rates of both faire positives and false negatives. Results f rom recent studies indicate the need to consider behavioral features in sel ecting candidates for fragile X screening. (C) 2000 Wiley-Liss, Inc.