X-linked Mental Retardation X-linked mental retardation (XLMR) broadly refers to a group of forms of inherited mental retardation with primary genetic defects in genes on the X chromosome. Although difficult to estimate, the prevalence of XLMR may be approximately 1:600 in affected males and 1:400 in female carriers. XLMR includes both syndromic and non-syndromic forms. Patients with XLMR are most commonly boys with developmental delay or mental retardation of variable severity, who usually have another affected male maternal relative (e.g., maternal uncle). Among the estimated 150-200 candidate genes on the X chromosome, fewer than 50 have been identified as responsible for XLMR. The majority of the identified genes are linked to syndromic XLMR, which can include a variety of systemic (non-CNS) manifestations. Genes associated with non-syndromic XLMR are unique in their association with the Rho GTPase signaling system, which regulates synaptic growth and connectivity by integrating extracellular and intracellular signals that modify the actin cytoskeleton. Because of the apparent “pure” neurobehavioral phenotype of non-syndromic XLMR, delineation of the molecular basis of this and other types of XLMR may not only contribute to improved strategies for clinical diagnosis and treatment of XLMR patients, but also to a better understanding of human cognitive development.