Beyond the Extra X and Y Chromosome: The Contribution of Familial Risk for Psychopathology to the Neurodevelopmental Phenotype of Children With Sex Chromosome Trisomy.

Individuals with an extra X or Y chromosome (sex chromosome trisomy or SCT) have an increased risk for symptoms of psychopathology and neurocognitive dysfunction. In this study, we evaluated the contribution of family history (FH) of neuropsychiatric or neurocognitive disorders to the phenotype of SCT. One hundred and six children with SCT and 102 nonclinical controls, all aged 1-7 years, and their primary caregiver (parent) participated. Rates of neuropsychiatric and neurocognitive disorders were collected for all first-degree family members of the children. Neurocognitive tests and parental questionnaires were used to evaluate children's neurobehavioral and neurocognitive phenotypes. Results showed no systematic differences in FH of neuropsychiatric and neurocognitive disorders between the SCT and control groups. No significant effect of a FH of psychiatric disorders was found on any of the child outcomes. FH of neurocognitive disorders had a single significant effect on child outcomes. Inattention problems in SCT were higher with a positive FH of neurocognitive disorders, showing dosage response effects. Familial factors may only minimally contribute to the overall phenotype of SCT on group level, although a positive FH of neurocognitive disorders may contribute to ADHD inattention symptoms in children with SCT, beyond the risk associated with the extra X or Y chromosome.