Molecular-Clinical Correlations in Children and Adults With Fragile X Syndrome

• Introduction. —Fragile X syndrome is the most commonly known inherited form of mental retardation. The intellectual abilities range from a normal IQ with learning disabilities to severe mental retardation. In males, there is a tendency for IQ decline in childhood. The purpose of this study was to correlate variations of the molecular cytosine guanine guanine (CGG) amplification in the fragile X mental retardation-1 (FMR-1) gene with the clinical findings, including IQ and physical features. Methods. —Full-scale IQ and cytogenetic results in 116 individuals with the FMR-1 mutation were studied. The IQ testing was performed with age-appropriate standardized tests. Physical features were summarized in a physical index score for each patient. The FMR-1 results were determined with the OX1.9 probe and the following system was used: P1 indicates premutation; P2, large premutation to small full mutation; P3, full mutation; and P4, mosaic. Results/Conclusions. —The findings showed that those females with a small insert in the P1 range had a significantly higher IQ than other heterozygotes (P2, P3, and P4 categories). P4 males had a significantly higher IQ than P2 or P3 males. In cross-sectional age comparisons, the slope of the IQ decline was greater in P2 males than in P4 or P3 males. ( AJDC . 1993;147:723-726)