The benefits and limitations of cell-free DNA screening for 47, XXY (Klinefelter syndrome)

Samango‐Sprouse, Carole; Keen, Colleen; Sadeghin, Teresa; Gropman, Andrea

doi:10.1002/pd.5044

Cited by 33 publications

(31 citation statements)

References 59 publications

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“…Current recommendations for the care of children with a prenatal diagnosis of 47,XXY are that they undergo comprehensive developmental assessments at 9–15 months, 18–24 months and 30–36 months . Therefore, prenatal screening for 47,XXY opens up new possibilities for early intervention and anticipatory care as well as challenges for individuals, families and health professionals that require careful consideration …”

Section: Discussionmentioning

confidence: 99%

Population‐based trends in the prenatal diagnosis of sex chromosome aneuploidy before and after non‐invasive prenatal testing

et al. 2018

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Objective To assess the impact of non‐invasive prenatal testing (NIPT) on trends in the prenatal diagnosis of sex chromosome aneuploidy (SCA) in a population with >73,000 annual births. Method Retrospective population‐based cohort study from 1986–2016 of all women undergoing prenatal diagnosis before 25 weeks gestation in the Australian state of Victoria. Statistical significance was tested using the chi‐square test for trend or proportions. Results There were 2,043,345 births and 842 SCA diagnoses from 1986–2016. The percentage of prenatal diagnostic tests leading to a SCA diagnosis increased significantly from 0.95% in 2010 to 2.93% in 2016 (p < 0.001) but due to a concurrent decline in testing, the annual prenatal diagnosis rate of SCA remained stable at 4.4/10,000 births. Among confirmed fetal SCAs the most common indication for testing in 1986 was advanced maternal age (63%); in 2016 it was high risk NIPT (49%). Conclusion SCAs now make up an increasing proportion of prenatal diagnostic results but due to the overall decline in diagnostic testing, the prenatal prevalence as a percentage of births remained steady. The ascertainment of fetal SCA has evolved from an incidental finding after testing for increased risk of trisomy 21, to a diagnosis obtained after suspected SCA on NIPT.

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Section: Discussionmentioning

confidence: 99%

Population‐based trends in the prenatal diagnosis of sex chromosome aneuploidy before and after non‐invasive prenatal testing

et al. 2018

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“…Over the last decade, the technology to detect genetic variations in unborn children has advanced significantly; one advantage being that they can be non‐invasive, for example by screening maternal blood. These advanced technological developments and the increased possibility to detect SCT during the pregnancy could lead to more individuals being diagnosed on the genetic, instead of the behavioral level . This calls for more knowledge about the development of (young) children with SCT, so children can get the appropriate support as early as possible when needed.…”

Section: Introductionmentioning

confidence: 99%

“…These advanced technological developments and the increased possibility to detect SCT during the pregnancy could lead to more individuals being diagnosed on the genetic, instead of the behavioral level. 13 This calls for more knowledge about the development of (young) children with SCT, so children can get the appropriate support as early as possible when needed. The identification of a profile of neurocognitive risks, and knowledge about the mechanisms underlying these risks, could help improve early screening for neurobehavioral problems in young children with SCT and help identify targets for early, tailored support and intervention programs, which in turn could hopefully optimize outcomes in later life.…”

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confidence: 99%

A review of neurocognitive functioning of children with sex chromosome trisomies: Identifying targets for early intervention

2019

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Sex chromosome trisomies (SCT) are among the most common chromosomal duplications in humans. Due to recent technological advances in non-invasive screening, SCT can already be detected during pregnancy. This calls for more knowledge about the development of (young) children with SCT. This review focused on neurocognitive functioning of children with SCT between 0 and 18 years, on domains of global intellectual functioning, language, executive functioning, and social cognition, in order to identify targets that could benefit from early treatment.Online databases were used to identify peer-reviewed scientific articles using specific search terms. In total 18 studies were included. When applicable, effect sizes were calculated to indicate clinical significance.Results of the reviewed studies show that although traditionally, the focus has been on language and intelligence (IQ) in this population, recent studies suggest that executive functioning and social cognition may also be significantly affected already in childhood.These findings suggest that neuropsychological screening of children diagnosed with SCT should be extended, to also include executive functioning and social cognition.Knowledge about these neurocognitive risks is important to improve clinical care and help identify targets for early support and intervention programs to accommodate for the needs of individuals with SCT.

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“…However, the application of noninvasive prenatal KS screening remains controversial because of the mild phenotypic presentation of KS, unsatisfactory sensitivity and specificity of testing, maternal anxiety, and the complications of genetic counseling. 22 23 Therefore, postnatal screening is preferred for comprehensive diagnosis of KS.…”

Section: Introductionmentioning

confidence: 99%

Rapid screening for Klinefelter syndrome with a simple high-resolution melting assay: a multicenter study

Zhou

Zhao³

et al. 2018

Asian J Androl

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Klinefelter syndrome (KS) is the set of symptoms that result from the presence of an extra X chromosome in males. Postnatal population-based KS screening will enable timely diagnosis of this common chromosomal disease, providing the opportunity for early intervention and therapy at the time point when they are most effective and may prevent later symptoms or complications. Therefore, through this study, we introduced a simple high-resolution melting (HRM) assay for KS screening and evaluated its clinical sensitivity and specificity in three medical centers using 1373 clinical blood samples. The HRM assay utilized a single primer pair to simultaneously amplify specific regions in zinc finger protein, X-linked (ZFX) and zinc finger protein, Y-linked (ZFY). In cases of KS, the ratios of ZFX/ZFY are altered compared to those in normal males. As a result, the specific melting profiles differ and can be differentiated during data analysis. This HRM assay displayed high analytical specificity over a wide range of template DNA amounts (5 ng–50 ng) and reproducibility, high resolution for detecting KS mosaicism, and high clinical sensitivity (100%) and specificity (98.1%). Moreover, the HRM assay was rapid (2 h per run), inexpensive (0.2 USD per sample), easy to perform and automatic, and compatible with both whole blood samples and dried blood spots. Therefore, this HRM assay is an ideal postnatal population-based KS screening tool that can be used for different age groups.

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The benefits and limitations of cell-free DNA screening for 47, XXY (Klinefelter syndrome)

Cited by 33 publications

References 59 publications

Population‐based trends in the prenatal diagnosis of sex chromosome aneuploidy before and after non‐invasive prenatal testing

Population‐based trends in the prenatal diagnosis of sex chromosome aneuploidy before and after non‐invasive prenatal testing

A review of neurocognitive functioning of children with sex chromosome trisomies: Identifying targets for early intervention

Rapid screening for Klinefelter syndrome with a simple high-resolution melting assay: a multicenter study

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