Fragile X syndrome — branching viva

Opening framework

My framework has four layers. First, the indication — any child with unexplained intellectual disability or developmental delay, especially a boy, and any child with autism and intellectual involvement, warrants fragile X testing. Second, the investigation — a two-part molecular assay of FMR1 PCR plus methylation analysis, because karyotype and microarray miss the repeat expansion. Third, the mechanism — a CGG-repeat expansion that methylates and silences FMR1, abolishing FMRP, the synaptic translational brake. Fourth, the family — cascade testing of the mother, siblings, and at-risk relatives, with premutation surveillance. ^[1]