Language phenotypes in children with sex chromosome trisomies

Abstract

Background Sex chromosome trisomies (47,XXX, 47,XXY and 47,XYY) are known to be a risk factor for language disorder, but it is hard to predict outcomes, because many cases are identified only when problems are found. Methods We recruited children aged 5-16 years with all three types of trisomy, and divided them into a High Bias group, identified in the course of investigations for neurodevelopmental problems, and a Low Bias group, identified via prenatal screening or other medical investigations. Children from a twin sample were used to compare pattern and severity of language problems: they were subdivided according to parental concerns about language/history of speech-language therapy into a No Concerns group (N = 118) and a Language Concerns group (N = 57). Children were assessed on a psychometric battery and a standardized parent checklist. After excluding children with intellectual disability, autism or hearing problems, the sample included 28 XXX, 18 XXY and 14 XYY Low Bias cases and 7 XXX, 13 XXY and 17 XYY High Bias cases. Results Variation within each trisomy group was substantial: within the Low Bias group, overall language scores were depressed relative to normative data, but around one third had no evidence of problems. There was no effect of trisomy type, and the test profile was similar to the Language Concerns comparison group. The rate of problems was much greater in the High Bias children with trisomies. Conclusions When advising parents after discovery of a trisomy, it is important to emphasise that, though there is an increased risk of language problems, there is a very wide range of outcomes. Severe language problems are more common in those identified via genetic testing for neurodevelopmental problems but these are not characteristic of children identified on prenatal screening.

Keywords: Klinefelter syndrome; Trisomy X; XYY syndrome; ascertainment bias; parent report; psychometric testing; variability.

Figure 1.. Numbers of children with sex chromosome trisomies included in different analyses.

Figure 2.. Numbers of twin children with and without language concerns.

Figure 3.. Distributions of scores on four clusters of psychometric tests for the Low Bias trisomy groups and the Language Concerns Comparison group.

Open circles show cases in age range 6 to 11 yr. Solid line is mean for 6–11 yr olds, dashed line is mean for whole sample including those outside 6–11 yr age range. Yellow band is mean +/- 1 SD for No Concern comparison group.

Figure 4.. Distributions of scores on four clusters of psychometric tests for the Low Bias vs High Bias trisomy groups.

Unfilled circles show cases in age range 6 to 11 yr, unfilled circles with a cross show older children, unfilled squares with cross show 5-year-olds. Cases with ASD (filled squares) and intellectual disability (filled diamonds) are included in the plot, but were excluded from the analysis comparing bias groups. Asterisk denotes High Bias group. Solid lines are group means for children included in MANOVA; dashed lines show means with ASD/ID cases included. Yellow band is mean +/- 1 SD for No Concern comparison group.

Figure 5.. Mean scores on the three CCC-2 composites for trisomy and comparison groups.

The yellow shaded band shows mean +/-1 SD for the No Concerns twin group. For trisomies, dashed lines show mean for whole group, and solid lines show means for children aged 6 to 11 years.

Figure 6.. Mean scores on the three CCC-2 composites for Low Bias vs High Bias trisomy groups, with the latter denoted by asterisks.

For trisomies, solid lines show mean for children included in MANOVA, and dashed lines show means for with cases of ASD or low IQ included. The yellow shaded band shows mean +/-1 SD for the No Concerns twin group.