A study of the physical, behavioral, and medical phenotype, including anthropometric measures, of females with fragile X syndrome
C. Hull and R. J. Hagerman
Child Development Unit, Children's Hospital, Denver, CO 80218.
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.
