To account for the data related to: (1) extensive FMR1 methylation in fetal tissues by the end of the first trimester; (2) the high rates of methylation mosaics among male patients; and (3) the wide variability in the epigenetic status of the expanded gene between and within the currently available FXS XY hESC lines, we proposed a temporal model of FMR1 hypermethylation (Figure 1) which suggests that abnormal methylation is first acquired stochastically on full expansions during a restricted point in time before or during embryo implantation. This evidence concerns the gene FMR1 and fragile X syndrome.