Prenatal Diagnosis Of Klinefelter Syndrome Research Articles

State-wide increase in prenatal diagnosis of klinefelter syndrome on amniocentesis and chorionic villus sampling: Impact of non-invasive prenatal testing for sex chromosome conditions.

To analyze population-based trends in the prenatal diagnosis of sex chromosome aneuploidy (SCA) since the availability of non-invasive prenatal testing (NIPT). Retrospective state-wide data for all prenatal diagnoses performed <25weeks gestation from 2005 to 2020 in Victoria, Australia. Non-invasive prenatal testing became locally available from 2012. The prenatal diagnosis rates of SCA as proportions of all prenatal diagnostic tests and all births were calculated. Statistical significance was assessed with the χ2 test for trend, with p<0.05 considered significant. 46,518 amniocentesis and chorionic villus sampling were performed during the study period, detecting 617 SCAs. There was a significant increase in the rate of prenatal SCAs from 5.8 per 10,000 births in 2005 to 8.7 per 10,000 births in 2020 (p<0.0001). This increase was predominantly due to 47,XXY cases, 91% of which were ascertained via positive NIPT for this condition in 2020. The prenatal diagnosis rate of 47,XXY significantly increased from 0.8 per 10,000 births in 2005 to 4.3 per 10,000 births in 2020 (p<0.0001). Screening for SCAs using NIPT has directly led to an increase in their prenatal diagnosis on a population-wide basis, especially 47,XXY. This has implications for clinician education, genetic counselling, and pediatric services.

952 Prenatal phenotype of 47,XXY (Klinefelter syndrome)

The phenotypic description of prenatal Klinefelter syndrome (KS), or 47,XXY, is currently limited to case reports. There is a gap in knowledge regarding prenatal presentation of KS. We hypothesize that a significant percentage of pregnancies complicated by fetal KS will have associated ultrasonographic findings. We retrospectively identified all fetuses with cytogenetically confirmed 47,XXY in the prenatal period or up to age 5 years, with prenatal records available for review from four prenatal diagnostic referral centers between 2006 and 2019. Ultrasound reports were reviewed to assess for the presence of increased nuchal translucency (NT) and abnormalities at the second trimester anatomy ultrasound. Additionally, we reviewed results of cell free DNA and serum analyte testing to inform our understanding of prenatal screening tests in the setting of fetal KS. A total of 42 subjects with confirmed cytogenetic diagnosis of 47,XXY and prenatal records available for review were identified: 38 had a prenatal diagnosis of KS and 4 had a postnatal diagnosis. One case was excluded as cytogenetic analysis demonstrated mosaic KS, leaving a cohort of 41 subjects. NT was increased ≥3.0mm in 6 of 26 (23.1%) of cases that had a documented measurement. A second trimester anatomical survey was available for review in 24/41 affected pregnancies. In 7 of 24 (29.2%) ultrasounds, a fetal abnormality was identified. These include 3 brain anomalies, 1 cardiac abnormality, 1 echogenic bowel, and 2 limb abnormalities (table). In subjects who had cell free DNA performed, 92.6% had a positive result for 47,XXY (25/27); in subjects who had serum analytes performed, 36.3% (4/11) had a positive result. This case series expands our knowledge of the prenatal presentation of KS by identifying 1st and 2nd trimester fetal sonographic abnormalities as well as serum analyte abnormalities.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Does the Fetus With Klinefelter Syndrome Have a Disproportionately Long Femur Length at the Anatomy Ultrasound? [9P

INTRODUCTION: To determine if children with a known diagnosis of Klinefelter Syndrome (KS) had a fetal anatomy ultrasound demonstrating long femur length (FL). METHODS: Case series of males with Klinefelter Syndrome (KS) receiving medical care in the pediatric endocrinology division at Thomas Jefferson University Hospital (TJUH) in 2014. We invited the mothers of these male children to participate in our study. Women who agreed to participate signed a medical records release form, which was sent to the delivering obstetrician requesting prenatal and delivery records. Records were reviewed for demographics, biometric measurements from the 18-22 week anatomy ultrasound, and delivery outcomes. Primary outcome was FL (calculated percentile based on Hadlock) from the anatomy ultrasound. RESULTS: In 2014, there were 100 males with KS being cared for at TJUH. 52 women agreed to participate in the study. We received medical records on 40 of these women (77%); of these, 30 records had the anatomy ultrasound report and delivery information. Mean gestational age at the time of the anatomy ultrasound 19.71 weeks (SD ± 1.29 weeks). 41% of women had an amniocentesis and a known prenatal diagnosis of KS. Femur length percentile was computed based on gestational age at the time of the ultrasound; mean FL percentile was 51.6% (SD ± 14.7%, range 8.7%-77.6%). CONCLUSION: The phenotype of males with Klinefelter Syndrome commonly results in tall stature, with a disproportionately long femur from early childhood. However, fetal femur length does not appear to predict an increased risk for Klinefelter Syndrome at the time of anatomy ultrasound.

Case Report of Prenatal Diagnosis of Klinefelter Syndrome Based on Ultrasound Screening

Case Report of Prenatal Diagnosis of Klinefelter Syndrome Based on Ultrasound Screening

The impact of prenatally diagnosed Klinefelter Syndrome on obstetric and neonatal outcomes

ObjectiveThe objective of this study was to examine the obstetric and neonatal outcomes as well as the as the associated hospital costs for pregnancies complicated by prenatally diagnosed Klinefelter Syndrome, 47,XXY. Study designWe conducted a retrospective cohort study of all of the singleton deliveries in California from 2005 to 2008 using vital statistics and ICD-9 data, specifically identifying cases of fetal Klinefelter Syndrome. Specifically, we were interested in the outcomes of preterm delivery, preeclampsia, intrauterine fetal demise, cesarean delivery, neonatal death, respiratory distress syndrome (RDS), small for gestational age, large for gestational age, neonatal death, and infant death. Bivariate and multivariate analyses were used to compare pregnancies and neonates affected by prenatally diagnosed Klinefelter Syndrome to those that were not affected with 47,XXY. ResultsThere were 2,029,000 deliveries in the cohort, including 52 women with prenatally diagnosed 47,XXY. Advanced maternal age, completion of 12th grade, and private insurance were all associated with a prenatal diagnosis of Klinefelter Syndrome. Compared to unaffected deliveries, pregnancies complicated by prenatally diagnosed Klinefelter Syndrome had higher rates of preterm delivery (23.1% vs 9.9%, p=0.0004), cesarean delivery (50.0% vs 30.2%, p=0.004), and RDS (9.6% vs 1.2%, p=<0.0001). Infants with 47,XXY were markedly more likely to be small for gestational age, including less than the 10th, 5th and 3rd percentile (aOR 5.86 (95% CI 2.99, 11.46), 6.03 (95% CI 2.52, 14.43), and 8.28 (95% CI 3.22, 21.25), p≤0.001). Rates of neonatal death were 9.5 times higher (1.9% vs 0.2% p<0.0001) in the 47,XXY cohort, and rates of infant death were more than 50 times higher (5.8% vs 0.1%, p<0.0001). In the adjusted analysis, prenatally diagnosed 47,XXY was associated with increased odds of preterm delivery <32 weeks (OR 6.81, 95% CI 2. .38, 19.52), IVH (OR 9.08, 95% CI 1.22, 67.7), RDS (OR 8.32, 95% CI 3.22, 21.49), neonatal death (OR 9.77, 1.33, 71.79), and infant death (OR 62.73, 95% CI 19.34, 203.4). ConclusionPregnancies affected by prenatally diagnosed Klinefelter Syndrome are at an increased risk of adverse fetal and neonatal outcomes. These findings may be helpful when counseling families with pregnancies affected by fetal 47,XXY.

Counselling of a couple faced with a prenatal diagnosis of Klinefelter syndrome

When a prenatal diagnosis of Klinefelter syndrome (KS) is made, a couple is faced with an unfamiliar and unexpected diagnosis. The aim of this article is to give clues to prenatal counselling in this situation. The information provided to couples facing a prenatal diagnosis of KS should ideally be based on longitudinal studies of unselected individuals, including those diagnosed prenatally. Indeed, there are several reasons to think that the phenotype of individuals diagnosed prenatally is globally less severe than in those diagnosed postnatally. Based on these studies, the evidence to be explained to couples to help them make an informed decision about the pregnancy is the following: except for rather tall height, generally normal appearance throughout life; increased risk of learning disabilities; spontaneous puberty, reduced testicular size, usual need for testosterone supplementation from adolescence onward; increased risk of gynecomastia; sexual orientation similar to the general male population; infertility, but with the possibility of having biological offspring with assisted reproductive techniques. In this article, we review the evidence about the phenotype of KS according to the circumstances of diagnosis and its use in counselling couples faced with a prenatal diagnosis of this common condition. Cohort studies including individuals with KS diagnosed prenatally are still lacking.

Proteomic analysis of amniotic fluid in pregnancies with Klinefelter syndrome foetuses

Klinefelter syndrome is a sex chromosomal abnormality (47, XXY karyotype), occurring approximately in 1 in 1000 male live births. In the present study proteomic analysis was performed in twelve 2nd trimester amniotic fluid samples, eight coming from pregnancies with normal males and four with Klinefelter syndrome foetuses, as shown by routine prenatal cytogenetic analysis. Samples were analysed by 2-DE, coupled with MALDI-TOF-MS analysis. Three proteins (Ceruloplasmin, Alpha-1-antitrypsin and Zinc-alpha-2-glycoprotein) were found to be up-regulated in samples obtained from pregnancies with Klinefelter syndrome foetuses, whereas four proteins (Apolipoprotein A-I, Plasma retinol-binding protein, Gelsolin, and Vitamin D-binding protein) were down regulated when compared to proteins detected in samples from normal foetuses. The differential expression of Ceruloplasmin, Apolipoprotein A-I and Plasma retinol-binding protein was further confirmed by immunoblotting. Since these proteins are likely to cross the placenta barrier and be detected in maternal plasma they could be used as biomarkers for the non-invasive prenatal diagnosis of Klinefelter syndrome.

Beckwith-Wiedemann Syndrome in a Patient with Klinefelter Syndrome

Beckwith-Widemann syndrome (BWS) is a well recognized clinical syndrome with a complex multi-genetic pathogenesis due to alterations in growth regulatory genes on chromosome 11p15. BWS has a frequency of 1 in 15000 live births. It is classically characterized by a triad of exomphalos, macroglossia and gigantism.Klinefelter syndrome is the most common cause of male hypogonadism with an estimated incidence of 1 in 500-1000 live born males. Chromosome studies most often show a 47 XXY karyotype.We report a newborn with a prenatal diagnosis of Klinefelter syndrome, and diagnosed to also have BWS after birth. This is a rare and interesting association with few previous reports in literature.

Providing information on Klinefelter syndrome

The aim of this study was to compare the information that midwives, obstetricians and geneticists report they would give parents following the prenatal diagnosis of Klinefelter syndrome. Fifty midwives, 135 obstetricians and 66 geneticists completed a brief questionnaire assessing the information they reported providing to parents following the prenatal diagnosis of Klinefelter syndrome. Geneticists reported providing more information about Klinefelter syndrome than midwives and obstetricians, particularly positive information about the condition. The information parents receive after the prenatal diagnosis of Klinefelter syndrome may vary according to the specialty of the health professionals consulted. This variation may reflect differences in the information these groups have about the condition. It remains to be determined whether such variation leads to different decisions about whether or not to continue with the pregnancy and subsequent parental adjustment.

Counselling following the Prenatal Diagnosis of Klinefelter Syndrome: Comparisons between Geneticists and Obstetricians in Five European Countries

Objective: To describe and compare the information obstetricians and geneticists in five European countries report they would give following the prenatal diagnosis of Klinefelter syndrome. Methods: 388 obstetricians and 269 geneticists from Germany, the Netherlands, Portugal, Spain and the UK completed a brief questionnaire assessing two variables: the information they reported providing to parents following the prenatal diagnosis of Klinefelter syndrome (categorized as positive or negative); and their perceptions of the quality of life with the condition. Results: Geneticists were more likely than obstetricians to report providing more positive than negative information about Klinefelter syndrome than equal amounts of positive and negative information or more negative than positive information about the condition (excess positive information). Regardless of specialty, the information that health professionals reported providing was predicted by their perceptions of the quality of life with the condition, and the country from which they came. Those perceiving quality of life as greater were more likely to provide an excess positive information, as were health professionals from Germany and the UK. Conclusions: These results suggest that the information parents across Europe receive after the prenatal diagnosis of Klinefelter syndrome varies according to the specialty and country of the health professionals consulted, and their perceptions of quality of life with the condition. This variation seems to reflect personal, cultural and professional differences between health professionals.