November 1993

A Study of the Physical, Behavioral, and Medical Phenotype, Including Anthropometric Measures, of Females With Fragile X Syndrome

Author Affiliations

From the Child Development Unit, The Children's Hospital (Ms Hull and Dr Hagerman), and the Department of Pediatrics, University of Colorado Health Sciences Center (Dr Hagerman), Denver.

Am J Dis Child. 1993;147(11):1236-1241. doi:10.1001/archpedi.1993.02160350110017

• 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.

(AJDC. 1993;147:1236-1241)