Neurocognitive and behavioral development in young children (1-7 years) with sex chromosome trisomy

Investigating sex chromosome trisomies (SCTs) may help in understanding neurodevelopmental pathways underlying the risk for neurobehavioral problems and psychopathology. Knowledge about the neurobehavioral phenotype is needed to improve clinical care and early intervention for children with SCT. This is especially relevant considering the increasing number of early diagnosed children with the recent introduction of noninvasive prenatal screening. The TRIXY Early Childhood Study is a longitudinal study designed to identify early neurodevelopmental risks in children with SCT, aged 1-7 years. This review summarizes the results from the TRIXY Early Childhood Study, focusing on early behavioral symptoms in areas of autism spectrum disorder, attention-deficit hyperactivity disorder, and communication disorders, and underlying neurocognitive mechanisms in domains of language, emotion regulation, executive functioning, and social cognition. Behavioral symptoms were assessed through structured behavior observation and parental questionnaires. Neurocognition was measured using performance tests, eyetracking, and psychophysiological measures of arousal. In total, 209 children aged 1-7 years were included: 107 children with SCT (33 XXX, 50 XXY, and 24 XYY) and 102 age-matched population controls. Study outcomes showed early behavioral symptoms in young children with SCT, and neurocognitive vulnerabilities, already from an early age onward. Neurobehavioral and neurocognitive difficulties tended to become more pronounced with increasing age and were rather robust, independent of specific karyotype, pre/postnatal diagnosis, or ascertainment strategy. A more longitudinal perspective on neurodevelopmental 'at-risk' pathways is warranted, also including studies assessing the effectiveness of targeted early interventions. Neurocognitive markers that signal differences in neurodevelopment may prove to be helpful in this. Focusing on early development of language, social cognition, emotion regulation, and executive functioning may help in uncovering early essential mechanisms of (later) neurobehavioral outcome, allowing for more targeted support and early intervention.