Articles

Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability and autism, affecting around 1 in 4,000 individuals globally. This review analyzes the complex neurodevelopment landscape of FXS, beginning with its genetic origin: the expansion of CGG trinucleotide repeats (>200) in the 5′-UTR of the FMR1 gene. This expansion triggers epigenetic silencing and the subsequent loss of Fragile X Messenger Ribonucleoprotein (FMRP), an essential modulator of synaptic plasticity and neuronal mRNA translation. Clinically, FXS presents as cognitive impairment, social phobia, and distinctive phenotypic traits, with significant phenotypic variability between males and females. Innovation in AI-driven drug discovery, antisense oligonucleotide (ASO), and CRISPR-based epigenome-editing therapies offers new prospects. In contrast, current management relies on behavioral interventions and symptomatic pharmacological support. However, it is challenging to translate molecular insights into clinical efficacy. This review highlights the urgent need for robust biomarkers and improved clinical trial designs to advance targeted therapeutic strategies for FXS.