Collaborative prospective study of the fragile X syndrome: one-year progress report

A prospective study of the fragile X syndrome [fra(X)] was initiated one year ago to refine the estimates of recurrence risks based on the phenotype of the mother and the family history of the syndrome. The basic unit of data consists of the description of the conceptus of women known to carry the fra(X) gene or of mothers of an isolated case. To date, information on 261 women and their conceptuses was ascertained primarily through prenatal diagnosis; these data are summarized here. Although tests of significance were limited due to small sample sizes in subgroups, the following trends were observed: 1) the penetrance of fra(X) site expression was 80% in both male and female conceptuses suggesting that fra(X) site expression is equally penetrant early in development; 2) the sex ratio at the time of prenatal diagnosis did not differ from one, indicating that selection against fra(X) fetuses, if any, does not differ among sexes; 3) the recurrence risk among offspring of borderline/mildly retarded mothers was higher than that among offspring of intellectually normal mothers; 4) the recurrence risk in offspring did not differ based on the mother's fra(X) site expression; and 5) the recurrence risk in offspring of mothers with isolated cases was slightly less (34%) than that of obligate carrier mothers (41%) although this was not significant. The potential use of these prospective data on the fra(X) syndrome is emphasized.