Dosage effects of X and Y chromosomes on language and social functioning in children with supernumerary sex chromosome aneuploidies: implications for idiopathic language impairment and autism spectrum disorders

Abstract

Background: Supernumerary sex chromosome aneuploidies (X/Y-aneuploidies), the presence of extra X and/or Y chromosomes, are associated with heightened rates of language impairments and social difficulties. However, no single study has examined different language domains and social functioning in the same sample of children with tri-, tetra-, and pentasomy X/Y-aneuploidy. The current research sought to fill this gap in the literature and to examine dosage effects of X and Y chromosomes on language and social functioning.

Methods: Participants included 110 youth with X/Y-aneuploidies (32 female) and 52 with typical development (25 female) matched on age (mean ∼12 years; range 4-22) and maternal education. Participants completed the Wechsler intelligence scales, and parents completed the children's communication checklist-2 and the social responsiveness scale to assess language skills and autistic traits, respectively.

Results: Both supernumerary X and Y chromosomes were related to depressed structural and pragmatic language skills and increased autistic traits. The addition of a Y chromosome had a disproportionately greater impact on pragmatic language; the addition of one or more X chromosomes had a disproportionately greater impact on structural language.

Conclusions: Given that we link extra X chromosomes with structural language impairments and an extra Y chromosome with pragmatic language impairments, X/Y-aneuploidies may provide clues to genetic mechanisms contributing to idiopathic language impairment and autism spectrum disorders.

Figure 1

Scores earned by participants by genotype. Overall group mean is indicated with solid dark line. Means for the XYY, XXY, and XXX PRE1, PRE2, and POST subgroups are indicated with dotted lines. Scores reported in Panels a–f are as follows: (a)WASI Estimated-VIQ, (b)WASI Estimated-PIQ, (c)CCC-2 Structural Language, (d)CCC-2 Pragmatic Language, (e)CCC-2 Social Interaction Difference Index, and (f) SRS Raw Score. Note that PRE1= Prenatally-diagnosed subgroup whose parents were not part of support group or joined when child was <1year; PRE2=Prenatally-diagnosed subgroup whose parents joined support group when child was >1year; POST=Postnatally diagnosed subgroup.

Figure 2

Cohen’s d effect size scores for primary dependent variables as a function of supernumerary X/Y-chromosome number. Panel (a) Effect sizes for the PRE1 trisomy groups (i.e., prenatally ascertained participants whose parents were not part of a support group or joined before the child’s first birthday) and Panel (b) Effects sizes for all participants regardless of ascertainment/recruitment