In prospective studies of young, fragile X [fra(X)] males with the full mutation, cognitive abilities (IQ scores) and adaptive behavior levels (DQ scores) declined in most subjects tested. Little is known about longitudinal changes in IQ and DQ scores in young fra(X) females, although one earlier retrospective study showed declines in IQ scores in 8 of 11 subjects. To examine fra(X) females prospectively, we tested and retested 13 females with the full mutation, age 4 to 15 years. Nine were tested and retested in North America, and four were evaluated at the Catholic University in Leuven, Belgium. Cognitive abilities of North American females were measured using the Stanford-Binet 4th Edition. Adaptive behavior levels were ascertained from the Vineland Adaptive Behavior Scales. For Belgians, test-retest scores from the Wechsler Intelligence Scales for Children-Revised were used. Subjects were subsequently separated into two age cohorts: those tested initially before age 7 years and those tested initially after age 7 years. Compared with young males with the full mutation and of the same age, females expectedly display a wider range of IQ scores. Test-retest IQ scores showed statistically significant decreases (P < 0.03). Analysis of individual test-retest scores indicate that declines in eight females were statistically significant. Adaptive behavior scores were available only for North American females. Five of nine (55%) showed significant declines in DQ. Like young males with the full mutation, all females with the full mutation attained higher adaptive behavior levels than cognitive scores, i.e., DQ > IQ.

We analyzed the metacarpophalangeal pattern profile (MCPP) on 18 male individuals from 16 families with fragile X-fra (X), or Martin-Bell-syndrome and calculated a mean syndrome profile. Fourteen of 18 individuals with fra (X) syndrome had significant positive correlations which indicated clinical homogeneity. Discriminant analysis of individuals with fra (X) syndrome compared with a sample of normal individuals produced a correct classification rate of 88% based on a function of 3 MCPP variables that may provide a useful tool in screening individuals for the fra (X) syndrome. Discriminant and correlation analyses of individuals with Sotos sequence and individuals with fra (X) syndrome did not identify MCPP similarities. Therefore, there was no MCPP evidence in our study of patients with Sotos sequence and fra (X) chromosome expression.

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.

No abstract

No abstract