A study of the physical, behavioral, and medical phenotype, including anthropometric measures, of females with fragile X syndrome.

The physical features of fragile X, including a long face, prominent ears, and hyperextensible joints, are present in affected males and females. Cytogenetically negative heterozygotes have been considered to be unaffected by the fragile X mental retardation-1 (FMR-1) gene. This study investigated the penetrance of the FMR-1 gene in cytogenetically negative but DNA-positive heterozygotes with a premutation (cytosine guanine guanine [CGG] amplification in the 50 to 200 repeat range), compared with carriers with a full mutation (> 200 CGG repeats) and control subjects. One hundred thirty-nine women with normal IQs between the ages of 18 and 45 years were studied. All underwent cytogenetic and DNA testing to determine their fragile X carrier status. A medical history-taking and a physical examination, including selected anthropometric measurements, were performed. Results indicate that the FMR-1 mutation mildly affects the physical phenotype of individuals even in the premutation state, although less dramatically than more affected heterozygotes. Carriers with a premutation differed significantly from control subjects in overall physical index score and in the anthropometric measure of ear prominence. These results suggest a phenotypic impact of the FMR-1 mutation even at the 50 to 200 CGG repeat length.