Forty-six unselected children with various sex chromosome abnormalities (14 boys with 47,XXY, 4 boys with 47,XYY, 11 girls with 47,XXX, 9 girls with 45,X, and 8 girls with SCA mosaicism), identified through the consecutive chromosome screening of 40,000 Denver newborns, have been followed developmentally and evaluated in a protocol that included intellectual, language, and achievement testing. Controls consisted of 12 chromosomally normal males and 13 chromosomally normal females who were siblings of various propositi. While most SCA children were not mentally retarded, most of the nonmosaic propositi (31/37) received special education help for learning problems. In general, nonmosaic males were less severely affected than nonmosaic females, who demonstrated significantly reduced mean IQ scores on both Wechsler IQ tests. The inference that learning disorders were genetically mediated in this group was further supported by karyotype-specific findings. 47,XXY boys tended to demonstrate lower verbal skills and a specific reading disability. 47,XXX girls, while more globally impaired, demonstrated evidence of a specific weakness in language skills. 45,X girls tended to be globally impaired, but demonstrated a contrasting specific deficit in spatial thinking skills. Mosaic girls were not significantly different than controls on any measure, an outcome likely occurring because of the low percentage of aneuploid cells in these propositae. Variability was present in each group, and no single profile can characterize all children with any specific SCA. The presence of SCA, therefore, must be viewed as a risk factor creating a tendency towards LD but interacting with a host of other genetic and environmental forces to create a range of phenotypic outcomes.
