Cognitive profiles and the spectrum of clinical manifestations in heterozygous fra(X) females

We investigated the possibility that fra(X) heterozygotes had a distinct or specific set of mental deficits ('cognitive profile') which would allow for accurate diagnosis. Wechsler Intelligence Scale for Children-Revised (WISC-R) subtest scores obtained on 8 fra(X) school age girls were compared with similar scores obtained on 8 'learning-disabled' non fra(X) girls matched on the basis of Full Scale IQ (FSIQ). The Block Design subtest score was significantly lower in fra(X) girls. In a larger sample of 22 fra(X) females, a characteristic combination of low Arithmetic, Digit Span, and Block Design subtest scores was observed. The mean discrepancy between these 3 subtest scores from the total Verbal or Performance subtest means was significant for the fra(X) group but not for a comparison group of 20 learning-disabled females. Verbal IQ (VIQ) and Performance IQ (PIQ) discrepancy was not significant in fra(X) females. Percent fra(X) positive cells was negatively correlated with VIQ and FSIQ but not with PIQ. This distinct cognitive profile suggests that the presence of the fra(X) gene causes a specific set of focal deficits. This profile, and the physical, behavioral, and emotional characteristics associated with the fra(X) syndrome, were found in several fra(X) females with normal FSIQs (>85). Our sample represents a spectrum of clinical involvement that extends from obvious degrees of impairment to normal intellectual function.