Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY), also known as aneuploidy, are often associated with an increased risk of neurodevelopmental disorders such as intellectual disability, behavioural problems, language difficulties, and autism spectrum disorder. However, many individuals show little or no evidence of neurodevelopmental difficulties. This wide range of severity within the same SCT diagnosis is termed “heterogeneity” - that two individuals who carry the same change may have very different outcomes. This is a major challenge in medical genetics research and is a key factor in improving the diagnosis of genetic conditions.
Here we consider if this “heterogeneity” is related to the presence of secondary copy number variants (CNVs) - stretches of deleted or duplicated DNA. We examine whether carrying more of these CNVs increases the chance of a neurodevelopmental condition. Or does this depend on which genes are affected by these CNVs, as we now know that some genes are more tolerant of these genetic variants than others?