MR is common, affecting approximately 1% to 3% of the general population and defined as an intelligence quotient (IQ) of <70, coupled with limitations in adaptive abilities.

The differentiation between mild and severe MR is clinically important because this helps to determine which educational programs are most beneficial for patients.

MR results from genetic and environmental factors. Genetics provide the cognitive potential, which is molded by environmental factors. Fragile X syndrome (FXS), fetal alcohol syndrome (FAS), and Down’s syndrome have been identified as the three most common identifiable causes of MR.

FXS is the leading cause of inherited MR. The prevalence of FXS is 1 in 4,000 males; 1:6,000 females. Approximately, 4% to 8% of the cases of MR in males are due to this syndrome. The primary mutation is an increase in the number of CGG trinucleotide repeats in the promoter region of the fragile X mental retardation gene (FMR1) on the X chromosome. Individuals with >230 CGG repeats have a “full mutation.” Those with a modest increase in repeats (55–230) are considered to have a “premutation.” Based on the mutation leading to this syndrome, it makes sense that the diagnosis of FXS is via molecular testing of the FMR1 gene to detect a CGG repeat expansion. Chromosome analysis to detect the fragile site of the X-chromosome is no longer used as a stand alone test because of its low sensitivity.