A review of neurocognitive functioning and risk for psychopathology in sex chromosome trisomy (47,XXY, 47,XXX, 47, XYY)
Open accessAbstract
PURPOSE OF REVIEW: About one in 650-1000 children is born with an extra X or Y chromosome, referred to as sex chromosome trisomies (SCTs). Studying SCTs may uncover unique insights in neurodevelopmental pathways underlying the risk for neurobehavioral problems and psychopathology. There is also a clinical need for more knowledge about the phenotype of SCT with the recent introduction of noninvasive prenatal screening. RECENT FINDINGS: The reviewed studies illustrate an increased vulnerability for psychopathology such as (symptoms of) autism spectrum disorder, attention-deficit/hyperactivity disorder, anxiety, depression and, to a lesser degree, psychotic disorders. Although traditionally the primary focus has been on language and learning problems, recent research suggests that impairments in executive functioning, social cognition and emotion regulation may also be key factors underlying the risk for neurobehavioral problems. SUMMARY: The research field of SCT is in need of a more longitudinal perspective to identify early markers of 'at risk' development, and to assess the effectiveness of early interventions. Neurocognitive markers that signal compromised neurodevelopment may prove to be helpful in this. Variability in the SCT phenotype provides a unique opportunity to identify not only genetic but also environmental factors that shape neurodevelopmental outcome, calling for studies focused on understanding individual differences.
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Autism diagnosis prevalence is almost double in individuals with XYY syndrome (on average 30%) than in individuals with XXY syndrome (18%) and XXX syndrome (15%), although it is still higher in individuals with the latter two syndromes than in the general population.
“For example, autism diagnosis prevalence is almost double in individuals with XYY syndrome (on average 30%) than in individuals with XXY syndrome (18%) and XXX syndrome (15%), although it is still higher in individuals with the latter two syndromes than in the general population239.”
From Sex and gender in neurodevelopmental conditions (2023) · cites this paper as [239]
Sex chromosome aneuploidies are associated with increased prevalence of autism, ADHD, and language and cognitive deficits, particularly in association with male phenotypes.
“Sex chromosome aneuploidies (SCA) are associated with increased prevalence of autism, ADHD, and language and cognitive deficits, particularly in association with male phenotypes239.”
From Sex and gender in neurodevelopmental conditions (2023) · cites this paper as [239]
ADHD symptoms and diagnoses are markedly increased across all three types of sex chromosome trisomy.
“ADHD symptoms and diagnoses are also markedly increased across all these three types of sex chromosome trisomy239.”
From Sex and gender in neurodevelopmental conditions (2023) · cites this paper as [239]
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Sex and gender in neurodevelopmental conditions
Bölte, S., Neufeld, J., Marschik, P. B., Williams, Z. J., Gallagher, L., & Lai, M.-C. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00774-6 · Cited by 249 · see citing works
Patterns of psychopathology and cognition in sex chromosome aneuploidy
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- Authors
- van Rijn, S.
- Venue
- Current Opinion in Psychiatry
- Published
- 2019-03
- Volume
- 32
- Issue
- 2
- Pages
- 79-84
- ISSN
- 0951-7367 (ISSN-L)
- PMC
- PMC6687415
- OpenAlex
- W2904712951
- Cited by
- 89
- References
- 55
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 10 · 2023: 16 · 2022: 23 · 2021: 11 · 2020: 8 · 2019: 2
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (452-16-005)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- sex chromosome trisomies, Klinefelter syndrome, 47,XXX, 47,XYY, neurocognitive function, psychopathology risk, autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, depression, psychosis, executive function, social cognition, emotion regulation, brain development, phenotypic variability, early intervention, noninvasive prenatal screening
- MeSH terms
- Self-Control, Humans, Psychopathology, Sex Chromosomes, Social Behavior, Trisomy, Early Intervention, Educational, Neurocognitive Disorders, Sex Chromosome Disorders, Executive Function
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