Introduction: Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability and is usually caused by a CGG expansion in the FMR1 gene and the associated epigenetic silencing. Recent studies have shown that FMR1 intron 1 methylation is significantly associated with verbal cognitive impairment in adults, but this has not been shown in children. Furthermore, variation in FMR1 intron 1 methylation between blood, saliva and buccal samples has not been previously described.  Methods: A cohort of 40 children carrier of FMR1 expanded alleles, depending on their age, were administered either The Mullen Scale of Early Learning, the Wechsler Preschool and Primary Scale of Intelligence III edition or The Wechsler Intelligence Scale for Children IV edition. Molecular parameters included CGGs repeats size and FMR1 Intron 1 methylation in venous blood, saliva and buccal swabs samples. Results: Preliminary analysis of 10 participants has shown a significant correlation between FMR1 intron 1 methylation in blood, saliva and buccal samples and overall cognitive functioning (p<.ooo1). There was no significant difference in methylation of this region between tissue types.  Discussion: FMR1 Intron 1 methylation can be analyzed in saliva and/or buccal swabs samples as a non-invasive alternative to venous blood for diagnosis of FXS. The pending analysis of the entire cohort with additional clinical data aims to unravel the potential prognostic applications of these biomarkers for the type and severity of neurodevelopmental impairments in FXS children.