Excessive negative regulation of type I interferon disrupts viral control in individuals with Down syndrome.

Down syndrome (DS) is typically caused by triplication of chromosome 21. Phenotypically, DS presents with developmental, neurocognitive, and immune features. Epidemiologically, individuals with DS have less frequent viral infection, but when present, these infections lead to more severe disease. The potent antiviral cytokine type I Interferon (IFN-I) receptor subunits IFNAR1 and IFNAR2 are located on chromosome 21. While increased IFNAR1/2 expression initially caused hypersensitivity to IFN-I, it triggered excessive negative feedback. This led to a hypo-response to subsequent IFN-I stimuli and an ensuing viral susceptibility in DS compared to control cells. Upregulation of IFNAR2 expression phenocopied the DS IFN-I dynamics independent of trisomy 21. CD14+ monocytes from individuals with DS exhibited markers of prior IFN-I exposure and had muted responsiveness to ex vivo IFN-I stimulation. Our findings unveil oscillations of hyper- and hypo-response to IFN-I in DS, predisposing individuals to both lower incidence of viral disease and increased infection-related morbidity and mortality.

Aneuploidy effects on human gene expression across three cell types.

Aneuploidy syndromes impact multiple organ systems but understanding of tissue-specific aneuploidy effects remains limited-especially for the comparison between peripheral tissues and relatively inaccessible tissues like brain. Here, we address this gap in knowledge by studying the transcriptomic effects of chromosome X, Y, and 21 aneuploidies in lymphoblastoid cell lines, fibroblasts and iPSC-derived neuronal cells (LCLs, FCL, and iNs, respectively). We root our analyses in sex chromosome aneuploidies, which offer a uniquely wide karyotype range for dosage effect analysis. We first harness a large LCL RNA-seq dataset from 197 individuals with one of 6 sex chromosome dosages (SCDs: XX, XXX, XY, XXY, XYY, and XXYY) to i) validate theoretical models of SCD sensitivity and ii) define an expanded set of 41 genes that show obligate dosage sensitivity to SCD and are all in cis (i.e., reside on the X or Y chromosome). We then use multiple complementary analyses to show that cis effects of SCD in LCLs are preserved in both FCLs (n = 32) and iNs (n = 24), whereas trans effects (i.e., those on autosomal gene expression) are mostly not preserved. Analysis of additional datasets confirms that the greater cross-cell type reproducibility of cis vs. trans effects is also seen in trisomy 21 cell lines. These findings i) expand our understanding of X, Y, and 21 chromosome dosage effects on human gene expression and ii) suggest that LCLs may provide a good model system for understanding cis effects of aneuploidy in harder-to-access cell types.

Health care satisfaction and medical literacy habits among caregivers of individuals with Down syndrome.

Patients with Down syndrome have significant specialized health care needs. Our objective was to understand the needs, satisfaction, and online habits of caregivers as they care for persons with Down syndrome. A mixed-method survey was distributed through REDCap from April 2022 to June 2022 in the United States; a Spanish-translated version was distributed through SurveyMonkey from August 2022 to March 2023 in Mexico. We received 290 completed responses from the United States and 58 from caregivers in Mexico. We found that current health care options are not meeting the needs of many individuals with DS in both the United States (39.7%) and Mexico (46.6%). Caregivers expressed frustrations with the inaccessibility and inapplicability of health care information. In particular, they often found the volume of information overwhelming, given their limited medical background. Additionally, health care recommendations were not customized and lacked practical recommendations. Most caregivers in both the United States (72.1%) and Mexico (82.8%) believe it is not easy to find answers to medical questions about their loved ones with DS. Online platforms with customized, specific health information related to DS could offer innovative solutions to these unmet needs for families and primary care providers.

Practicalities (and real-life experiences) of dementia in adults with Down syndrome.

Adults with down syndrome (DS) have a lifetime dementia risk in excess of 95%, with a median age of onset of 55 years, due to trisomy 21. Co-occurring Alzheimer's disease (AD) has increased morbidity and mortality, and it is now recommended to screen for AD in all adults with DS beginning at 40 years of age. In this manuscript, we present two clinical cases of adults with DS who developed AD summarizing their medical histories, presenting symptoms, path to diagnosis and psychosocial aspects of care collected from retrospective chart review with caregiver consent. These two cases were chosen due to their complexity and interwoven nature of the medical and psychosocial aspects, and highlight the complexity and nuance of caring for patients with DS and AD.

Sustainability of personal social networks of people with Down syndrome.

Research continues to demonstrate that the characteristics of one's social network could have an impact on the development of Alzheimer's disease. Given the predisposition of people with Down syndrome to develop Alzheimer's disease, analysis of their social networks has become an emerging focus. Previous pilot research demonstrated that the personal networks of people with DS could be quantitatively analyzed, with no difference between self-report and parent-proxy report. This manuscript focuses on a 12-month follow-up period with the same original participants (24 adults with Down syndrome). Their social networks demonstrated sustainability, but not improvement, as reported by people with DS (mean network size: 8.88; mean density: 0.73; mean constraint: 0.44; mean effective size: 3.58; mean max degree: 6.04; mean degree: 4.78) and their proxies (mean network size: 7.90; mean density: 0.82; mean constraint: 53.13; mean effective size: 2.87; mean max degree: 5.19; mean degree: 4.30). Intentional and continued efforts are likely needed in order to improve the social network measures of people with Down syndrome.

Retrospective review of the code status of individuals with Down syndrome during the COVID-19 era.

Code status is a label in the medical record indicating a patient's wishes for end-of-life (EOL) care in the event of a cardiopulmonary arrest. People with intellectual disabilities had a higher risk of both diagnosis and mortality from coronavirus infections (COVID-19) than the general population. Clinicians and disability advocates raised concerns that bias, diagnostic overshadowing, and ableism could impact the allocation of code status and treatment options, for patients with intellectual disabilities, including Down syndrome (DS). To study this, retrospective claims data from the Vizient® Clinical Data Base (used with permission of Vizient, all rights reserved.) of inpatient encounters with pneumonia (PNA) and/or COVID-19 at 825 hospitals from January 2019 to June 2022 were included. Claims data was analyzed for risk of mortality and risk of "Do Not Resuscitate" (DNR) status upon admission, considering patient age, admission source, Elixhauser comorbidities (excluding behavioral health), and DS. Logistic regression models with backward selection were created. In total, 1,739,549 inpatient encounters with diagnoses of COVID-19, PNA, or both were included. After controlling for other risk factors, a person with a diagnosis of DS and a diagnosis of COVID-19 PNA had 6.321 odds ratio of having a DNR status ordered at admission to the hospital compared with those with COVID-19 PNA without DS. The diagnosis of DS had the strongest association with DNR status after controlling for other risk factors. Open and honest discussions among healthcare professionals to foster equitable approaches to EOL care and code status are needed.

All Creatures Great and Small: New Approaches for Understanding Down Syndrome Genetics.

Human chromosome 21 (Hsa21) contains more than 500 genes, making trisomy 21 one of the most complex genetic perturbations compatible with life. The ultimate goal of Down syndrome (DS) research is to design therapies that improve quality of life for individuals with DS by understanding which subsets of Hsa21 genes contribute to DS-associated phenotypes throughout the lifetime. However, the complexity of DS pathogenesis has made developing appropriate animal models an ongoing challenge. Here, we examine lessons learned from a variety of model systems, including yeast, nematode, fruit fly, and zebrafish, and discuss emerging methods for creating murine models that better reflect the genetic basis of trisomy 21.

Results of inaugural international Down Syndrome Societal Services and Supports survey.

PURPOSE: We previously designed the Down Syndrome Societal Services and Supports Survey (DS-4S) to measure country-specific supports for people with Down syndrome (DS) across multiple life domains (healthcare, education, policy, independence, and community inclusion). We now report and analyze the results. METHODS: We partnered with international DS consortia, who distributed the DS-4S to 154 cumulative members representing over 100 countries. Organizations were included if they had a holistic focus on the lives of people with DS and if at least 50% of their members either have DS or are family members of people with DS. Factor analysis was used to analyze the results. RESULTS: We received survey responses from 55 different organizations in 50 countries who met inclusion criteria. Each country had complete data for at least 4 of the 5 domains. The lowest 5 scores were from countries in Africa and Asia; the highest 5 scores were in Europe and North America. CONCLUSION: The responses to the DS-4S stratified countries within each surveyed domain. The DS-4S can now be used to track countries' progress over time and to determine which countries have best practices that might be replicated. We will publish the results and update them biennially at www.DownSyndromeQualityOfLife.com.

Senescent hearts from male Ts65Dn mice exhibit preserved function but altered size and nicotinamide adenine dinucleotide pathway signaling.

Down syndrome (DS) is associated with congenital heart defects at birth, but cardiac function has not been assessed at older ages. We used the Ts65Dn mouse, a model of DS, to quantify heart structure and function with echocardiography in 18-mo male Ts65Dn and wild-type (WT) mice. Heart weight, nicotinamide adenine dinucleotide (NAD) signaling, and mitochondrial (citrate synthase) activity were investigated, as these pathways may be implicated in the cardiac pathology of DS. The left ventricle was smaller in Ts65Dn versus WT, as well as the anterior wall thickness of the left ventricle during both diastole (LVAW_d; mm) and systole (LVAW_s; mm) as assessed by echocardiography. Other functional metrics were similar between groups including left ventricular area end systole (mm2), left ventricular area end diastole (mm2), left ventricular diameter end systole (mm), left ventricular diameter end diastole (mm), isovolumetric relaxation time (ms), mitral valve atrial peak velocity (mm/s), mitral valve early peak velocity (mm/s), ratio of atrial and early peak velocities (E/A), heart rate (beats/min), ejection fraction (%), and fractional shortening (%). Nicotinamide phosphoribosyltransferase (NAMPT) protein expression, NAD concentration, and tissue weight were lower in the left ventricle of Ts65Dn versus WT mice. Sirtuin 3 (SIRT3) protein expression and citrate synthase activity were not different between groups. Although cardiac function was generally preserved in male Ts65Dn, the altered heart size and bioenergetic disturbances may contribute to differences in aging for DS.

RUN(X) out of blood: emerging RUNX1 functions beyond hematopoiesis and links to Down syndrome.

BACKGROUND: RUNX1 is a transcription factor and a master regulator for the specification of the hematopoietic lineage during embryogenesis and postnatal megakaryopoiesis. Mutations and rearrangements on RUNX1 are key drivers of hematological malignancies. In humans, this gene is localized to the 'Down syndrome critical region' of chromosome 21, triplication of which is necessary and sufficient for most phenotypes that characterize Trisomy 21. MAIN BODY: Individuals with Down syndrome show a higher predisposition to leukemias. Hence, RUNX1 overexpression was initially proposed as a critical player on Down syndrome-associated leukemogenesis. Less is known about the functions of RUNX1 in other tissues and organs, although growing reports show important implications in development or homeostasis of neural tissues, muscle, heart, bone, ovary, or the endothelium, among others. Even less is understood about the consequences on these tissues of RUNX1 gene dosage alterations in the context of Down syndrome. In this review, we summarize the current knowledge on RUNX1 activities outside blood/leukemia, while suggesting for the first time their potential relation to specific Trisomy 21 co-occurring conditions. CONCLUSION: Our concise review on the emerging RUNX1 roles in different tissues outside the hematopoietic context provides a number of well-funded hypotheses that will open new research avenues toward a better understanding of RUNX1-mediated transcription in health and disease, contributing to novel potential diagnostic and therapeutic strategies for Down syndrome-associated conditions.

Parents of children with Down syndrome reflect on their postnatal diagnoses, 2003-2022.

A 2003 survey revealed the scope of mothers' dissatisfaction with their postnatal support following a diagnosis of Down syndrome (DS). Substantial proportions of mothers reported that providers conveyed diagnoses with pity, emphasized negative aspects of DS, and neglected to provide adequate materials explaining DS. This study follows up on the 2003 survey by assessing whether parents' experiences have improved. Four DS nonprofit organizations, which participated in the original study, distributed a mixed-methods survey to families who have had children with DS between 2003 and 2022. Quantitative analysis assessed correlations among responses and differences between the 2003 and 2022 survey groups. Open-ended responses were qualitatively analyzed. Compared to the 2003 findings, parents' perceptions of their postnatal care have not improved (N = 89). Parents are increasingly likely to report that their providers pitied them, omitted positive aspects of DS, and provided insufficient materials describing DS. Substantial proportions of parents reported fear (77%) and anxiety (79%), only 24% described receiving adequate explanatory materials, and parents were 45% likelier to report that physicians discussed negative aspects of DS than positive aspects. Qualitatively, substantial numbers of parents recounted insensitive conduct by providers. These results suggest that despite interventions, parents' experiences of postnatal diagnoses of DS have not improved over time. Certain provider behaviors-such as describing positive aspects of DS and providing comprehensive explanatory materials-can reduce fear and anxiety, pointing to directions for reform.

Clinical implications of crown-rump length discordance at 11 to 14 weeks in dichorionic twins.

BACKGROUND: Crown-rump length discordance, defined as ≥10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance. OBJECTIVE: This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance. STUDY DESIGN: This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders. RESULTS: Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance. CONCLUSION: Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers.

Efficacy and safety of adenotonsillectomy in the management of obstructive sleep apnea syndrome in children with Down syndrome: A systematic review and meta-analysis.

Obstructive sleep apnea (OSA) is commonly observed in children with Down syndrome (DS) and may affect their physical and psychological development. Currently, adenotonsillectomy is the first line treatment option for paediatric patients with OSA. However, surgical outcomes for such patients are not satisfactory. In this study, we analysed the efficacy and safety of adenotonsillectomy in the treatment of children with obstructive sleep apnea and Down syndrome. We systematically searched the PubMed, Web of Science, EMBASE, and the Cochrane databases and pooled data from nine relevant studies involving 384 participants. Subsequently, we analysed four outcomes in polysomnography, namely: net postoperative changes in the apnea-hypopnea index (AHI), the minimum oxygen saturation, sleep efficiency, and arousal index. Meta-analysis of the AHI showed a decrease of 7.18 events/h [95% CI (-9.69, -4.67) events/h; p < 0.00001] and an increase in the minimum oxygen saturation of 3.14% [95% CI (1.44, 4.84) %; p = 0.0003]. There was no significant increase in sleep efficiency [MD 1.69%, 95% CI (-0.59, 3.98) %; p = 0.15], but the arousal index significantly decreased by -3.21 events/hour [95% CI (-6.04, -0.38) events/h; p < 0.03]. In addition, the overall success rate was 16% (95% CI, 12%-21%) for postoperative AHI < 1 and 57% (95% CI, 51%-63%) for postoperative AHI <5. The postoperative complications recorded included airway obstruction and bleeding. This study demonstrated the efficacy of adenotonsillectomy as a treatment option for OSA. However, it is important to note that residual OSA and potential postoperative complications require further attention in future studies.

Follow-up of children with Down syndrome and sleep disordered breathing and the effects of treatment on actigraphically recorded sleep, quality of life, behaviour, and daytime functioning.

Children with Down syndrome are at increased risk of obstructive sleep disordered breathing, which has deleterious effects on daytime functioning. We aimed to examine the effects of treatment of sleep disordered breathing on sleep quality and daytime functioning in children with Down syndrome, and hypothesised that these would be improved. Thirty-four children completed a baseline study and a follow-up 2 years later. Measures at both time points included 7 days of actigraphy and parents completed a number of questionnaires assessing sleep, behaviour, daytime functioning, and quality of life. All children had overnight polysomnography at baseline; 15 children (44%) were treated. At baseline the treated group had more severe sleep disordered breathing compared with the untreated group: obstructive apneoa-hypopnoea index 29.3 ± 38.2 events/h versus 3.3 ± 5.2 events/h (p < 0.01). Actigraphy showed no significant differences in total sleep time, sleep efficiency, sleep schedules from baseline to follow up in either group. The sleep disturbance (p < 0.01) and total problems (p < 0.05) scales on the OSA-18 and the sleep disordered breathing subscale on the Paediatric Sleep Problem Survey Instrument (p < 0.01) improved in the treated children. There were no changes in any measure in the untreated children. Treatment of sleep disordered breathing improves symptoms, sleep disturbance and quality of life in children with Down syndrome, but has no demonstrable impact on actigraphic sleep measures or daytime behaviour or function. In contrast, children who were not treated, despite having less severe disease at baseline, had increased sleep disruption and no change in quality of life.

Comparison of power spectra from overnight electroencephalography between patients with Down syndrome and matched control subjects.

Electroencephalograms can capture brain oscillatory activities during sleep as a form of electrophysiological signals. We analysed electroencephalogram recordings from full-night in-laboratory polysomnography from 100 patients with Down syndrome, and 100 age- and sex-matched controls. The ages of patients with Down syndrome spanned 1 month to 31 years (median 4.4 years); 84 were younger than 12 years, and 54 were male. From each electroencephalogram, we extracted relative power in six frequency bands or rhythms (delta, theta, alpha, slow sigma, fast sigma, and beta) from six channels (frontal F3 and F4, central C3 and C4, and occipital O1 and O2) during five sleep stages (N3, N2, N1, R and W)-180 features in all. We examined differences in relative power between Down syndrome and control electroencephalograms for each feature separately. During wake and N1 sleep stages, alpha rhythms (8.0-10.5 Hz) had significantly lower power in patients with Down syndrome than controls. Moreover, the rate of increase in alpha power with age during rapid eye movement sleep was significantly slower in Down syndrome than control subjects. During wake and N1 sleep, delta rhythms (0.25-4.5 Hz) had higher power in patients with Down syndrome than controls. During N2 sleep, slow sigma rhythms (10.5-12.5 Hz) had lower power in patients with DS than controls. These findings extend previous research from routine electroencephalogram studies demonstrating that patients with Down syndrome had reduced circadian amplitude-the difference between wake alpha power and deep sleep delta power was smaller in Down syndrome than control subjects. We envision that these brain oscillatory activities may be used as surrogate markers for clinical trials for patients with Down syndrome.

Guideline for treating relapsed or refractory myeloid leukemia in children with Down syndrome.

Treatment of relapsed and refractory myeloid leukemia in Down syndrome (r/r ML-DS) poses significant challenges, as prognosis is dire and there is no established standard treatment. This guideline provides treatment recommendations based on a literature review and collection of expert opinions, aiming to improve overall and event-free survival of patients. Treatment options include fludarabine and cytarabine (FLA) ± gemtuzumab ozogamicin (GO), azacytidine (AZA) ± panobinostat, and hematopoietic stem cell transplantation (HSCT). Preferred approaches are AZA ± panobinostat for cases with low blast count or FLA ± GO for cases with high blast count, followed by HSCT after remission. Further research is crucial for the investigation of targeted therapies (e.g., BH3 mimetics, LSD1, JAK inhibitors).

Myeloid Proliferations Associated with Down Syndrome: Clinicopathologic Characteristics of Forty Cases from Five Large Academic Institutions.

INTRODUCTION: The incidence of myelodysplastic syndrome and acute myeloid leukemia is significantly increased in children with Down syndrome (DS). Within the revised 2016 WHO edition, these entities are jointly classified as myeloid leukemia associated with DS (ML-DS). Additionally, infants with DS may develop transient abnormal myelopoiesis (TAM) which is histomorphologically similar to ML-DS. While TAM is self-limiting, it is associated with an increased risk of subsequently developing ML-DS. Differentiating TAM and ML-DS is challenging but clinically critical. METHODS: We performed a retrospective review of ML-DS and TAM cases collected from five large academic institutions in the USA. We assessed clinical, pathological, immunophenotypical, and molecular features to identify differentiating criteria. RESULTS: Forty cases were identified: 28 ML-DS and 12 TAM. Several features were diagnostically distinct, including younger age in TAM (p < 0.05), as well as presentation with clinically significant anemia and thrombocytopenia in ML-DS (p < 0.001). Dyserythropoiesis was unique to ML-DS, as well as structural cytogenetic abnormalities aside from the constitutional trisomy 21. Immunophenotypic characteristics of TAM and ML-DS were indistinguishable, including the aberrant expression of CD7 and CD56 by the myeloid blasts. DISCUSSION: The findings of the study confirm marked biological similarities between TAM and ML-DS. At the same time, several significant clinical, morphological, and genetic differences were observed between TAM and ML-DS. The clinical approach and the differential diagnosis between these entities are discussed in detail.

Diagnostic accuracy of cell-free DNA in maternal blood in detecting chromosomal anomalies in twin pregnancies: systematic review and meta-analysis.

OBJECTIVES: To report the diagnostic accuracy of cell-free DNA (cfDNA) in maternal blood in detecting chromosomal anomalies in twin pregnancies. METHODS: Medline, Embase and Cochrane databases were searched. The inclusion criteria were twin pregnancies undergoing cfDNA screening for Trisomies 13, 18, 21, monosomy X0 and other sex chromosomal anomalies (SCA). The index test was represented by a positive results of cfDNA test. The reference standard was represented by the karyotype results (obtained either pre or postnatally) or, in case of negative cfDNA result, by a normal neonatal phenotype. The quality of the studies was assessed using the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR), with the corresponding 95% Confidence Intervals (95% CI), were computed using the bivariate random-effects model. RESULTS: Thirty-five studies were included. cfDNA had an overall high accuracy in detecting Trisomy 21 in twin pregnancies with a sensitivity of 98.8% (95% CI 96.5-100), a specificity of 100% (95% CI 99.9-100). Sensitivity and specificity were of 94.9% (95% CI 75.6-99.1) and 100 (95% CI 99.9-100) for Trisomy 18, and 84.6% (95% C% 54.6-98.1) and 100% (95% CI 99.9-100) for Trisomy 13 . We could not compute the diagnostic accuracy of cfDNA in detecting monosomy X0 in twins, while cfDNA had a sensitivity of 100% (95% CI 71.5-100) and a specificity of 99.8% (95% CI 99.7-99.9) in detecting other SCA (11 cases). The accuracy of cfDNA in detecting Trisomy 21, 18 and 13 was similar in dichorionic and monochorionic twin pregnancies. CONCLUSION: cfDNA has a high diagnostic accuracy in detecting Trisomy 18 and 21 in twin pregnancies, irrespective of chorionicity. Accuracy in the detection of Trisomy 13 and SCA was limited by the small number of affected cases and the difficulties in the confirmation of false negative cases in case of SCA and requires confirmation in larger studies. This article is protected by copyright. All rights reserved.

The mismatch negativity as an index of cognitive abilities in adults with Down syndrome.

Down syndrome (DS) is associated with an ultra-high risk of developing Alzheimer's disease (AD). Understanding variability in pre-AD cognitive abilities may help understand cognitive decline in this population. The mismatch negativity (MMN) is an event-related potential component reflecting the detection of deviant stimuli that is thought to represent underlying memory processes, with reduced MMN amplitudes being associated with cognitive decline. To further understand the MMN in adults with DS without AD, we explored the relationships between MMN, age, and cognitive abilities (memory, language, and attention) in 27 individuals (aged 17-51) using a passive auditory oddball task. Statistically significant MMN was present only in 18 individuals up to 41 years of age and the latency were longer than canonical parameters reported in the literature. Reduced MMN amplitude was associated with lower memory scores, while longer MMN latencies were associated with poorer memory, verbal abilities, and attention. Therefore, the MMN may represent a valuable index of cognitive abilities in DS. In combination with previous findings, we hypothesize that while MMN response and amplitude may be associated with AD-related memory loss, MMN latency may be associated with speech signal processing. Future studies may explore the potential impact of AD on MMN in people with DS.

Correlation between telomere shortening in maternal peripheral blood and fetal aneuploidy.

BACKGROUND: This study aimed to assess whether maternal telomere length is a more accurate predictor of trisomy 21 than maternal age while also exploring the factors influencing maternal and fetal telomere length. METHODS: Forty mothers with fetuses carrying extra maternal copies of chromosome 21 were defined as trisomy 21 cases, and 18 mothers with normal karyotype fetuses were defined as controls. Telomere lengths of maternal blood lymphocytes and amniotic fluid cells were determined using real-time polymerase chain reaction. Fetal and maternal telomere lengths were compared between the two groups. Moreover, we analyzed the factors influencing maternal and fetal telomere length in the trisomy 21 pedigree. A logistic regression model was used to analyze the correlation between maternal telomere length and trisomy 21 risk. In addition, receiver operating characteristic (ROC) curve analysis was used to determine the accuracy of using maternal telomere length as an indicator of trisomy 21 risk. RESULTS: The study revealed that both maternal and fetal telomere lengths were significantly shorter in trisomy 21 cases than in the controls. In the trisomy 21 group, the maternal age, occupation, and nationality showed no significant correlation with their telomere length; fetal telomere length exhibited a positive correlation with maternal telomere length. Furthermore, maternal telomere length shortening is associated with trisomy 21 (OR = 0.311; 95% CI, 0.109-0.885, P < 0.05). The results of ROC curve analysis indicated that a combined assessment of maternal age and maternal telomere length predicted fetal chromosome trisomy more effectively than a single assessment (area under the curve 0.808, 95% CI, 0.674-0.941, P < 0.001). CONCLUSION: Maternal age combined with maternal telomere length proved to be a superior predictor of trisomy risk. Additionally, maternal telomere length was found to influence fetal telomere length.