Neurocognitive outcomes of individuals with a sex chromosome trisomy: XXX, XYY, or XXY: a systematic review*

Abstract

AimTo review systematically the neurodevelopmental characteristics of individuals with sex chromosome trisomies (SCTs).MethodA bibliographic search identified English-language articles on SCTs. The focus was on studies unbiased by clinical referral, with power of at least 0.69 to detect an effect size of 1.0.ResultsWe identified 35 articles on five neonatally identified samples that had adequate power for our review. An additional 11 studies were included where cases had been identified for reasons other than neurodevelopmental concerns. Individuals with an additional X chromosome had mean IQs that were within broadly normal limits but lower than the respective comparison groups, with verbal IQ most affected. Cognitive outcomes were poorest for females with XXX. Males with XYY had normal-range IQs, but all three SCT groups (XXX, XXY, and XYY) had marked difficulties in speech and language, motor skills, and educational achievement. Nevertheless, most adults with SCTs lived independently. Less evidence was available for brain structure and for attention, social, and psychiatric outcomes. Within each group there was much variation.InterpretationIndividuals with SCTs are at risk of cognitive and behavioural difficulties. However, the evidence base is slender, and further research is needed to ascertain the nature, severity, and causes of these difficulties in unselected samples.

Counseling parents before prenatal diagnosis: Do we need to say more about the sex chromosome aneuploidies?

“…Cognitive ability is reduced (verbal IQ-18 points, performance IQ-11 points [Leggett et al, 2010]. Mean IQ of 91 compared with 109 in normal male siblings and controls Lower level of motor activity, pliant disposition, cautious approach to new situations, few behavioral problems.…”

“…hemisphere) [Leggett et al, 2010;Tartaglia et al, 2012]. Individuals with 47,XXY will need endocrinological evaluation at 8-10 years of age and possible treatment after counseling about the chance of sperm cryo-conservation [Foresta et al, 1999;Oates, 2012].…”

Children with sex chromosome trisomies: parental disclosure of genetic status

“…7,8 Unwarranted by the careful caveats posed by researchers who carried out those studies, their reporting in the press led to widespread misunderstandings about individuals with SCTs, particularly presenting males with XYY as aggressive criminals, 9 whereas current evidence suggests that outcomes for these individuals are much more positive. 10 Several newborn screening studies were carried out in the 1960s to investigate outcomes in children with SCTs in samples unbiased by concerns prior to referral. [11][12][13][14] These longitudinal studies followed children who were diagnosed perinatally with an SCT into adulthood.…”

Sex chromosome trisomies in Europe: prevalence, prenatal detection and outcome of pregnancy

“…The relatively small amount of information available from population-based studies indicate that individuals with SCT are at increased risk of educational failure and neurodevelopmental disorder, with mean IQ broadly within the normal limits but reduced 10-20 points when compared with siblings; the biggest reduction in IQ being associated with XXX females. 5,[7][8][9][10] Some SCT cases are identified by chance prenatally when karyotyping is performed for different reasons, 11 for example, after a higher risk Down's syndrome screening test. Parents are then faced with the knowledge that their baby has a condition about which there is a lack of information available from unbiased studies.…”

“…Some of the information given may be outdated, inaccurate and unduly negative because of the ascertainment bias inherent in small select populations in the studies of affected children. [7][8][9][11][12][13] Termination of pregnancy for fetal anomaly (TOPFA) is requested by some parents after prenatal diagnosis of a SCT. Rates of prenatal detection, information given to parents and differences in laws and practices regarding termination of pregnancy are some factors which may lead to differences in outcome.…”