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Background: We developed a decision aid (DA) to help pregnant women and their partners make informed decisions about prenatal screening for trisomy. We aimed to determine its usefulness for preparing for decision-making and its acceptability among end-users.Methods: In this mixed-methods pilot study, we recruited participants in three prenatal care settings in Quebec City. Eligible women were over 18 and more than 16 weeks pregnant or had given birth recently. We asked them about the usefulness of the DA using an interview grid based on the Technology Acceptance Model. We performed descriptive statistics and deductive analysis.Results: Thirty-nine dyads or individuals participated in the study. Mean usefulness score was 86.2 ± 13. Most participants found the amount of information in the DA just right (79.5%), balanced (89.7%), and very useful (61.5%). They were less satisfied with the presentation and the values worksheet and suggested different values clarification methods.Conclusion: Rigorous pilot tests of DAs with patients are an important stage in their development before the more formal assessments that precede scaling up the DA in clinical practice.Practice Implications: The next version of the DA will integrate the suggestions of end-users for better decision-making processes about prenatal screening for trisomy. [ABSTRACT FROM AUTHOR]

Soft markers were originally introduced to prenatal ultrasonography to improve the detection of trisomy 21 over that achievable with age-based and serum screening strategies. As prenatal genetic screening strategies have greatly evolved in the last 2 decades, the relative importance of soft markers has shifted. The purpose of this document is to discuss the recommended evaluation and management of isolated soft markers in the context of current maternal serum screening and cell-free DNA screening options. In this document, "isolated" is used to describe a soft marker that has been identified in the absence of any fetal structural anomaly, growth restriction, or additional soft marker following a detailed obstetrical ultrasound examination. In this document, "serum screening methods" refers to all maternal screening strategies, including first-trimester screen, integrated screen, sequential screen, contingent screen, or quad screen. The Society for Maternal-Fetal Medicine recommends the following approach to the evaluation and management of isolated soft markers: (1) we do not recommend diagnostic testing for aneuploidy solely for the evaluation of an isolated soft marker following a negative serum or cell-free DNA screening result (GRADE 1B); (2) for pregnant people with no previous aneuploidy screening and isolated echogenic intracardiac focus, echogenic bowel, urinary tract dilation, or shortened humerus, femur, or both, we recommend counseling to estimate the probability of trisomy 21 and a discussion of options for noninvasive aneuploidy screening with cell-free DNA or quad screen if cell-free DNA is unavailable or cost-prohibitive (GRADE 1B); (3) for pregnant people with no previous aneuploidy screening and isolated thickened nuchal fold or isolated absent or hypoplastic nasal bone, we recommend counseling to estimate the probability of trisomy 21 and a discussion of options for noninvasive aneuploidy screening through cell-free DNA or quad screen if cell-free DNA is unavailable or cost-prohibitive or diagnostic testing via amniocentesis, depending on clinical circumstances and patient preference (GRADE 1B); (4) for pregnant people with no previous aneuploidy screening and isolated choroid plexus cysts, we recommend counseling to estimate the probability of trisomy 18 and a discussion of options for noninvasive aneuploidy screening with cell-free DNA or quad screen if cell-free DNA is unavailable or cost-prohibitive (GRADE 1C); (5) for pregnant people with negative serum or cell-free DNA screening results and an isolated echogenic intracardiac focus, we recommend no further evaluation as this finding is a normal variant of no clinical importance with no indication for fetal echocardiography, follow-up ultrasound imaging, or postnatal evaluation (GRADE 1B); (6) for pregnant people with negative serum or cell-free DNA screening results and isolated fetal echogenic bowel, urinary tract dilation, or shortened humerus, femur, or both, we recommend no further aneuploidy evaluation (GRADE 1B); (7) for pregnant people with negative serum screening results and isolated thickened nuchal fold or absent or hypoplastic nasal bone, we recommend counseling to estimate the probability of trisomy 21 and discussion of options for no further aneuploidy evaluation, noninvasive aneuploidy screening through cell-free DNA, or diagnostic testing via amniocentesis, depending on clinical circumstances and patient preference (GRADE 1B); (8) for pregnant people with negative cell-free DNA screening results and isolated thickened nuchal fold or absent or hypoplastic nasal bone, we recommend no further aneuploidy evaluation (GRADE 1B); (9) for pregnant people with negative serum or cell-free DNA screening results and isolated choroid plexus cysts, we recommend no further aneuploidy evaluation, as this finding is a normal variant of no clinical importance with no indication for follow-up ultrasound imaging or postnatal evaluation (GRADE 1C); (10) for fetuses with isolated echogenic bowel, we recommend an evaluation for cystic fibrosis and fetal cytomegalovirus infection and a third-trimester ultrasound examination for reassessment and evaluation of growth (GRADE 1C); (11) for fetuses with an isolated single umbilical artery, we recommend no additional evaluation for aneuploidy, regardless of whether results of previous aneuploidy screening were low risk or testing was declined. We recommend a third-trimester ultrasound examination to evaluate growth and consideration of weekly antenatal fetal surveillance beginning at 36 0/7 weeks of gestation (GRADE 1C); (12) for fetuses with isolated urinary tract dilation A1, we recommend an ultrasound examination at ≥32 weeks of gestation to determine if postnatal pediatric urology or nephrology follow-up is needed. For fetuses with urinary tract dilation A2-3, we recommend an individualized follow-up ultrasound assessment with planned postnatal follow-up (GRADE 1C); (13) for fetuses with isolated shortened humerus, femur, or both, we recommend a third-trimester ultrasound examination for reassessment and evaluation of growth (GRADE 1C). [ABSTRACT FROM AUTHOR]

Down syndrome (trisomy 21) is a common identifiable cause of intellectual disability. People with Down syndrome are individuals, and while there are many shared characteristics, there is considerable variability in how the syndrome manifests. Understanding the condition and its impact on individual lives can help maintain and promote health, and enable individuals to achieve their potential. There are some conditions that are more frequently seen in individuals with Down syndrome, and as such it is important not to fall into the trap of labelling all symptoms as 'part of Down syndrome'. Awareness of some of the more frequently seen conditions will help in understanding and aid timely investigation and management - enabling individuals to access the support and care they need. In this article, we focus on our role as health professionals in supporting families, children and young people with Down syndrome. We describe some of the conditions seen more commonly in individuals with Down syndrome and our role in screening, identification and management of these. [ABSTRACT FROM AUTHOR]

Background: Due to trisomy of chromosome 21 and the resultant extra copy of the amyloid precursor protein gene, nearly all adults with Down syndrome develop Alzheimer's disease pathology by the age of 40 years and are at high risk for dementia given their increased life expectancy compared with adults with Down syndrome in the past. We aimed to compare CSF biomarker patterns in Down syndrome with those of carriers of autosomal dominant Alzheimer's disease mutations to enhance our understanding of disease mechanisms in these two genetic groups at high risk for Alzheimer's disease.Methods: We did a cross-sectional study using data from adults enrolled in the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study, a multisite longitudinal study of Alzheimer's disease in Down syndrome, as well as a cohort of carriers of autosomal dominant Alzheimer's disease mutations and non-carrier sibling controls enrolled in the Dominantly Inherited Alzheimer Network (DIAN) study. For ABC-DS, participants with baseline CSF, available clinical diagnosis, and apolipoprotein E genotype as of Jan 31, 2019, were included in the analysis. DIAN participants with baseline CSF, available clinical diagnosis, and apolipoprotein E genotype as of June 30, 2018, were evaluated as comparator groups. CSF samples obtained from adults with Down syndrome, similarly aged carriers of autosomal dominant Alzheimer's disease mutations, and non-carrier siblings (aged 30-61 years) were analysed for markers of amyloid β (Aβ1-40, Aβ1-42); tau phosphorylated at threonine 181-related processes; neuronal, axonal, or synaptic injury (total tau, visinin-like protein 1, neurofilament light chain [NfL], synaptosomal-associated protein 25); and astrogliosis and neuroinflammation (chitinase-3-like protein 1 [YKL-40]) via immunoassay. Biomarker concentrations were compared as a function of dementia status (asymptomatic or symptomatic), and linear regression was used to evaluate and compare the relationship between biomarker concentrations and age among groups.Findings: We assessed CSF samples from 341 individuals (178 [52%] women, 163 [48%] men, aged 30-61 years). Participants were adults with Down syndrome (n=41), similarly aged carriers of autosomal dominant Alzheimer's disease mutations (n=192), and non-carrier siblings (n=108). Individuals with Down syndrome had patterns of Alzheimer's disease-related CSF biomarkers remarkably similar to carriers of autosomal dominant Alzheimer's disease mutations, including reductions (all p<0·0080) in Aβ1-42 to Aβ1-40 ratio and increases in markers of phosphorylated tau-related processes; neuronal, axonal, and synaptic injury (p<0·080); and astrogliosis and neuroinflammation, with greater degrees of abnormality in individuals with dementia. Differences included overall higher concentrations of Aβ and YKL-40 (both p<0·0008) in Down syndrome and potential elevations in CSF tau (p<0·010) and NfL (p<0·0001) in the asymptomatic stage (ie, no dementia symptoms).Funding: National Institute on Aging, Eunice Kennedy Shriver National Institute of Child Health and Human Development, German Center for Neurodegenerative Diseases, and Japan Agency for Medical Research and Development. [ABSTRACT FROM AUTHOR]

Objective: Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT).Study Design: A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth.Results: Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21.Conclusion: These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT. [ABSTRACT FROM AUTHOR]

Down syndrome screening has been available within clinical practice for over 50 years within which time significant innovation and exciting new advances have improved the accuracy, safety, and choice for women who are considering antenatal screening for Down syndrome. The UK National Screening Committee is responsible for setting the national standards regarding screening and it has steadily and consistently directed and facilitated an increase in the detection rate whilst minimising the screen positive rate. This has reduced the number of false positive results and consequently the number of invasive diagnostic procedures and their related miscarriages. Non-invasive pre-natal testing (NIPT) using cell free DNA is a rapidly evolving field and it will soon be incorporated into the existing NHS antenatal screening programme for aneuploidy. It will be offered to women who receive a 'high risk' result following current screening methods (combined test or quadruple test), and will further reduce the number of invasive tests performed, whilst maintaining current detection rates. [ABSTRACT FROM AUTHOR]

Objective: Noninvasive prenatal diagnosing for fetal trisomy 21 could help to avoid unnecessary amniocentesis. It is feasible to target the cell-free placental-specific mRNA in maternal plasma, thus eliminating the interference from the maternal genetic background.Study Design: In this study, placental-specific genes on chromosome 21 were identified by searching the TiGER database and reviewing the published literature. These cell-free placental-specific mRNA fragments in maternal plasma were amplified and sequenced. Then, the allelic ratio of heterozygous single-nucleotide polymorphisms(SNPs) was analyzed.Results: Four placental-specific genes (DNMT3L, KRTAP26-1, PLAC4, DSCR4) were identified. This study included 42 cases of normal pregnancies and 19 cases of trisomy 21 pregnancies. The probability density function showed that the allelic ratio of heterozygous SNPs in normal pregnancy reached a peak at 1.0, and that in the trisomy 21 pregnancy was a double-peaked curve in both 0.5 and 2.0. However, the allelic ratio of heterozygous SNPs demonstrated no statistical difference between the normal and trisomy 21 pregnancies.Conclusion: Fetal trisomy 21 could not be diagnosed by examining the heterozygous SNPs of cell-free placental-specific mRNA on chromosome 21. This might be because the low quantity and quality of cell-free placental-specific mRNA fragments in maternal plasma, and the limited available heterozygous SNPs on the placental-specific genes. [ABSTRACT FROM AUTHOR]

Down syndrome (DS) is more detrimental to language acquisition compared to other forms of learning disability. It has been shown that early social communication skills are important for language acquisition in the typical population; however few studies have examined the relationship between early social communication and language in DS. The aim of the current study is to compare the relationship between joint attention and concurrent language skills, and maternal interactive style and concurrent language skills in infants with DS and in typically developing (TD) infants matched for mental age. We also investigated if these relationships differ between children with DS and TD children. Twenty-five infants with DS (17-23 months) and 30 TD infants (9-11 months) were assessed on measures of joint attention, maternal interactive style and language. The results indicated a significant positive relationship between responding to joint attention (RJA) and concurrent language for the DS group, and a significant positive relationship between maternal positive expressed emotion (PEEM) and concurrent language for the TD group. We hypothesise that different social-communication factors are associated with language skills in DS, at least between 17 and 23 months of age compared to TD infants of similar non-verbal and general language abilities. [ABSTRACT FROM AUTHOR]

Background: Fragile X Syndrome (FXS) and Down Syndrome (DS) are common causes of Intellectual Disability (ID). Mothers of individuals with FXS sometimes have the premutation condition which makes them display neurocognitive signs, such as impulsiveness impairments, while mothers of DS individuals, as a group, do not have impairments. Although behavior problems in individuals with ID may be related to high Expressed Emotion (EE) in parents, parenting in families with ID members has been little explored.Aim: To explore the relationship between a mother's EE and impulsiveness, in mothers of individuals with FXS and DS, with behavior problems in their offspring.Method: A questionnaire was developed to collect data about impulsiveness and EE in mothers, along with information about behavior problems in ID individuals.Results: EE scores were associated with behavior problems in their offspring for both samples. Mothers with the premutation showed higher scores in EE than mothers of DS individuals. However, impulsiveness scores were not different between both parental groups, and were related to EE scores.Conclusions: EE is a parental feature that is possible to modulate and seems to be related to behavior problems in ID individuals. More research should be carried on to create interventions to reduce this attitude in parents of ID individuals. [ABSTRACT FROM AUTHOR]

Background: Children with Down syndrome (DS) are known for their reduced balance control, and typically take longer to develop motor skills and display less coordinated movement patterns. Hopping in-place is a gross motor skill requiring whole-body vertical stiffness and horizontal movement control, particularly when attempting to modify hopping frequency. However, there is a lack of knowledge of the hopping capacity of children with DS.Research Question: The purpose of this study was to assess the ability of children with DS aged 5-11 years old to continuously hop in-place on two legs and compare their biomechanical patterns to those of typically developing (TD) children.Methods: This observational study included 14 children with DS and 16 TD children. Subjects were asked to complete 20 s trials of two-legged hopping in-place at a self-selected frequency, and four metronome guided conditions: preferred (self-selected frequency), moderate (20% increase), fast (40% increase) and slow (20% decrease). Two sample independent t-tests were conducted on whole-body vertical stiffness, horizontal center-of-mass movement, and toe displacement between hops for the self-selected hopping condition and two-way ANOVAs were used for the metronome conditions.Results and Significance: Our findings suggest that children with DS might not be able to continuously hop in-place until the age of 7 years old, and were unable to hop for as long in duration as their TD peers. Children with DS self-selected a faster hopping frequency, and demonstrated an increased medial-lateral center-of-mass movement during the stance phase of hopping, suggesting reduced balance control. Moreover, children with DS were unable to correctly modify their hopping frequency when cued by a metronome and exhibited an inability to modulate whole-body vertical stiffness and constrain horizontal or vertical movement. These results demonstrate the utility of a future hopping intervention to improve whole-body vertical stiffness and balance control in children with DS. [ABSTRACT FROM AUTHOR]

Background Non-invasive prenatal screening (NIPS) of trisomy 21 (T21) using digital PCR (dPCR) with several advantages will be very effective. Here, we developed a dPCR system for T21 screening which allows high sensitivity and real-time diagnosis and thus overcome sequence based analysis. Methods Cut-off value was established using DNA extracted from all 157 T21 negative samples including 47 pregnant woman samples and 3 T21 positive pregnant woman samples extracted from 4 different sample types. To increase the portion of the cell-free fetal DNA (cffDNA) in maternal cell-free DNA (cfDNA), a size selection method was devised. We evaluated the clinical reliability of NIPS using dPCR through analysis of 877 pregnant woman samples. Results We could demonstrate the possibility of NIPS using dPCR performed by applying cut-off value and size selection method. The overall accuracy was derived at 99.66% using 877 pregnant woman plasma samples. Conclusion Our results showed that dPCR can meet the requirements for NIPS for T21. It is relatively inexpensive, easy to use in a screening method and compatible with ethical concerns regarding access to nucleotide sequence information. This study may be a basic data for the development of population-wide screening for T21 in pregnant women. [ABSTRACT FROM AUTHOR]

Objectives: To examine the costs and outcomes of different screening strategies for Down Syndrome (DS) in singleton pregnancies.Study Design: A decision-analytic model was developed to compare the costs and the outcomes of different prenatal screening strategies. Five strategies were compared for women under 35-year of age: 1A) triple test (TT), 2A); combined test (CT), 3A) Non-invasive Prenatal Screening Test by using cell free fetal DNA (NIPT), 4A) and 5A) NIPT as a second-step screening for high-risk patients detected by either TT, or CT respectively. For women ≥35-year of age, 1B) implementing invasive test (amniocentesis -AC) and 2B) NIPT for all women were compared. Data was analyzed to obtain the outcomes, total costs, the cost per women and the incremental cost-effectiveness ratios (ICERs) for screening strategies.Results: Among the current strategies for women under 35 years old, CT is clearly dominated to TT, as it is more effective and less costly. Although, the current routine practice (2A) is the least-costly strategy, implementing NIPT as a second step screening to high-risk women identified by CT (5A) would be more effective than 2A; leading to a 10.2% increase in the number of detected DS cases and a 96.3% reduction in procedural related losses (PRL). However, its cost to the Social Security Institution that is a public entity would be 17 times higher and increase screening costs by 1.5 times. Strategy 5A would result in an incremental cost effectiveness of 6,873,082 (PPP) US$ when compared to the current one (2A). Strategy 1B-for offering AC to all women ≥35-year of age is dominated over NIPT (2B), as it would detect more DS cases and would be less costly. On the other hand, there would be 206 PRL associated with AC, but NIPT provides clear clinical benefits as there would be no PRL with NIPT.Conclusions: NIPT leads to very high costs despite its high effectiveness in terms of detecting DS cases and avoiding PRL. The cost of NIPT should be decreased, otherwise, only individuals who can afford to pay from out-of-pocket could benefit. We believe that reliable cost-effective prenatal screening policies are essential in countries with low and smiddle income and high birth rates as well. [ABSTRACT FROM AUTHOR]

Down screening has been available within clinical practice for over 50 years during which time significant innovation and exciting new advances have improved the accuracy and safety of screening, and improved choice for women who are considering antenatal screening for Down syndrome. The UK National Screening Committee is responsible for setting the national standards regarding screening and it has steadily and consistently directed and facilitated an increase in the detection rate whilst minimising the screen positive rate of Down syndrome screening. This has reduced the number of false positive results and consequently the number of invasive diagnostic procedures and their related miscarriages. Non-invasive pre-natal testing (NIPT) using cell free DNA is a rapidly evolving field and it will soon be incorporated into the existing NHS antenatal screening programme for aneuploidy. It will be offered to women who receive a ‘high risk’ result following current screening methods (combined test or quadruple test), and will further reduce the number of invasive tests performed, whilst maintaining current detection rates. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the use of simulated experiences to communicate statistical information can improve an individual's understanding of conditional probabilities-specifically the positive predictive value (PPV) of prenatal screening tests for Down syndrome.Methods: In Experiment 1 (N=64) and Experiment 2 (N=180) participants were asked to estimate the PPV of a prenatal screening test for Down syndrome based on either (1) explicit statistics regarding the prevalence of Down syndrome and the sensitivity and specificity of a prenatal screening test for Down syndrome, or (2) experiencing up to 5000 simulated test results over a short time.Results: Participants' estimates of the PPV were more accurate when they had learned via simulated experiences (79% accuracy) compared with estimates based on explicitly described statistics (14%). Participants in the simulated experience condition also reported decreased interest in screening and decreased concern with a positive test result.Conclusion: Simulated experiences improve PPV estimates, compared to estimates derived from explicitly provided statistics, while also shifting attitudes away from screening.Practice Implications: The use of simulated experiences may prove to be simple but powerful tool to communicate complex statistical information to patients in medical decision making situations. [ABSTRACT FROM AUTHOR]

Objective: Sleep-disordered breathing (SDB) is highly prevalent in children with Down syndrome. Given the scarcity of resources and the presence of risk factors for SDB in this population, the objective of this study is to identify the clinical predictors of SDB, which would assist prioritization of children with Down syndrome for SDB evaluation.Methods: A retrospective cohort study was conducted on children enrolled in the Down syndrome clinic at CHEO who underwent polysomnography in 2004-2014. Total apnea-hypopnea index (AHI) or obstructive AHI (OAHI) > 5 events/hour was considered clinically significant. Associations between SDB and concurrent diagnoses, referral reasons, and sleep symptoms assessed by questionnaire were examined using Pearson's chi-square test or Fisher's exact test as appropriate. Univariate and multivariate logistic regression analyses were used to examine the predictors of SDB.Results: SDB was present in 42.9% of 119 children, with its highest prevalence at age 8 years. Symptoms were not significantly associated with AHI > 5 events/hour or OAHI > 5 events/hour. Gastroesophageal reflux was associated with lower odds of OAHI > 5 events/hour on univariate testing (odds ratio 0.16, 95% CI 0.04-0.72; p = 0.02) and multivariate analysis (odds ratio 0.05, 95% CI 0.0006-0.50; p = 0.002).Conclusions: SDB is highly prevalent at all ages in children with Down syndrome. Symptoms did not predict SDB in this population, although gastroesophageal reflux may mimic SDB, which indicates that clinicians should continue to perform ongoing surveillance for SDB throughout the lifespan of children with Down syndrome. [ABSTRACT FROM AUTHOR]

Individuals with Down syndrome (DS) are more likely to experience earlier onset of multiple facets of physiological aging. This includes brain atrophy, beta amyloid deposition, cognitive decline, and Alzheimer's disease—factors indicative of brain aging. Here, we employed a machine learning approach, using structural neuroimaging data to predict age (i.e., brain-predicted age) in people with DS (N = 46) and typically developing controls (N = 30). Chronological age was then subtracted from brain-predicted age to generate a brain-predicted age difference (brain-PAD) score. DS participants also underwent [ 11 C]-PiB positron emission tomography (PET) scans to index the levels of cerebral beta amyloid deposition, and cognitive assessment. Mean brain-PAD in DS participants' was +2.49 years, significantly greater than controls ( p < 0.001). The variability in brain-PAD was associated with the presence and the magnitude of PiB-binding and levels of cognitive performance. Our study indicates that DS is associated with premature structural brain aging, and that age-related alterations in brain structure are associated with individual differences in the rate of beta amyloid deposition and cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Even though Down syndrome is the most common chromosomal cause of intellectual disability, studies on early development are scarce.Aim: To describe movements and postures in 3- to 5-month-old infants with Down syndrome and assess the relation between pre- and perinatal risk factors and the eventual motor performance.Methods and Procedures: Exploratory study; 47 infants with Down syndrome (26 males, 27 infants born preterm, 22 infants with congenital heart disease) were videoed at 10-19 weeks post-term (median=14 weeks). We assessed their Motor Optimality Score (MOS) based on postures and movements (including fidgety movements) and compared it to that of 47 infants later diagnosed with cerebral palsy and 47 infants with a normal neurological outcome, matched for gestational and recording ages.Outcomes and Results: The MOS (median=13, range 10-28) was significantly lower than in infants with a normal neurological outcome (median=26), but higher than in infants later diagnosed with cerebral palsy (median=6). Fourteen infants with Down syndrome showed normal fidgety movements, 13 no fidgety movements, and 20 exaggerated, too fast or too slow fidgety movements. A lack of movements to the midline and several atypical postures were observed. Neither preterm birth nor congenital heart disease was related to aberrant fidgety movements or reduced MOS.Conclusions and Implications: The heterogeneity in fidgety movements and MOS add to an understanding of the large variability of the early phenotype of Down syndrome. Studies on the predictive values of the early spontaneous motor repertoire, especially for the cognitive outcome, are warranted.What This Paper Adds: The significance of this exploratory study lies in its minute description of the motor repertoire of infants with Down syndrome aged 3-5 months. Thirty percent of infants with Down syndrome showed age-specific normal fidgety movements. The rate of abnormal fidgety movements (large amplitude, high/slow speed) or a lack of fidgety movements was exceedingly high. The motor optimality score of infants with Down syndrome was lower than in infants with normal neurological outcome but higher than in infants who were later diagnosed with cerebral palsy. Neither preterm birth nor congenital heart disease were related to the motor performance at 3-5 months. [ABSTRACT FROM AUTHOR]

This study investigated the effectiveness of the Computerized Visual Perception Training (CVPT) program on individuals with Down syndrome (DS, mean age=13.17±4.35years, age range: 6.54-20.75 years). All participants have mild intellectual disability classified by the standard IQ measures (mean=61.2, ranges from 55 to 68). Both the Test of Visual Perceptual Skill- Third Edition (TVPS-3) and functional magnetic resonance imaging (fMRI) were used to evaluate the training outcomes. Results of TVPS-3 and fMRI showed that DS group had visual perceptual deficits and abnormal neural networks related to visual organization. The results showed that DS intervention group had significant improvements on TVPS-3 after intervention. The fMRI results indicated more activation in superior and inferior parietal lobes (spatial manipulation), as well as precentral gyrus and dorsal premotor cortex (motor imagery) in DS intervention group. The CVPT program was effective in improving visual perceptual functions and enhancing associated cortical activations in DS. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate sleep consolidation and circadian activity rhythms in infants and toddlers with Down syndrome (DS) under light and socially entrained conditions within a familiar setting. Given previous human and animal data suggesting intact circadian regulation of melatonin across the day and night, it was hypothesized that behavioral indices of circadian rhythmicity would likewise be intact in the sample with DS.Methods: A cross-sectional study of 66 infants and young children with DS, aged 5-67 months, and 43 typically developing age-matched controls. Sleep and measures of circadian robustness or timing were quantified using continuous in-home actigraphy recordings performed over seven days. Circadian robustness was quantified via time series analysis of rest-activity patterns. Phase markers of circadian timing were calculated alongside these values. Sleep efficiency was also estimated based on the actigraphy recordings.Results: This study provided further evidence that general sleep quality is poor in infants and toddlers with DS, a population that has sleep apnea prevalence as high as 50% during the preschool years. Despite poor sleep quality, circadian rhythm and phase were preserved in children with DS and displayed similar developmental trajectories in cross-sectional comparisons with a typically developing (TD) cohort. In line with past work, lower sleep efficiency scores were quantified in the group with DS relative to TD children. Infants born with DS exhibited the worst sleep fragmentation; however, in both groups, sleep efficiency and consolidation increased across age. Three circadian phase markers showed that 35% of the recruitment sample with DS was phase-advanced to an earlier morning schedule, suggesting significant within-group variability in the timing of their daily activity rhythms.Conclusions: Circadian rhythms of wake and sleep are robust in children born with DS. The present results suggest that sleep fragmentation and any resultant cognitive deficits are likely not confounded by corresponding deficits in circadian rhythms. [ABSTRACT FROM AUTHOR]

Background Down syndrome (DS) is the most common chromosomal aberration, but the characteristics of the brainstem component in this condition during childhood (from newborn to preteen stages) have not been clarified. Objective To evaluate the morphological features of the brainstem in DS on magnetic resonance imaging (MRI). Materials and methods MRIs for 32 children with DS (16 boys and girls each; age range, 0–11 years) without major brain insults, and 32 age-matched controls (16 boys and girls each) were retrospectively analyzed. Height, width, and area of the midbrain, pons, and medulla oblongata were measured on sagittal T1-weighted images; these were compared in children with DS and age-matched controls. The ratios of the brainstem to the size of the posterior fossa (BS/PF index) were calculated; these were also compared in the children with DS and the control group. Results The width and area of the midbrain; height, width, area of the pons; and area of the medulla oblongata were significantly smaller in children with DS than in control children ( P < 0.05); the area of the pons, particularly for the ventral part, showed the largest differences in the mean relative differences. The BS/PF indices of the height, width, and area of the pons were significantly smaller in children with DS than in the control group ( P < 0.01). However, the BS/PF indices for the midbrain and the medulla oblongata did not differ between these two groups. Conclusions Children with DS may have small brainstems, particularly in the pons; this may be a characteristic morphological feature of the brainstem on MRI in childhood including neonates. [ABSTRACT FROM AUTHOR]

Background Neopterin is an unconjugated pteridine that is secreted in large quantities by activated macrophages and can be used as a clinical marker of activated cellular immunity and oxidative stress. We aimed to investigate whether urinary neopterin levels are associated with cognitive function in people with Down syndrome (DS). Methods Out of 32 adults with DS who originally participated in a longitudinal study, 25 were followed up at 4 years. Informants rated their adaptive behavior (ABAS) and the adults with DS attempted assessments of language skills and memory at both baseline and follow-up time points (Modified Memory Object Task, MOMT), and receptive vocabulary (British Picture Vocabulary Scale, BPVS). Results Neopterin/creatinine levels were negatively correlated with change in the MOMT total score (Spearman’s Rho = −0.517, p = 0.020) and change in the MOMT delayed recall score (Spearman’s Rho = −0.577, p = 0.008) over time, i.e. higher neopterin/creatinine level was associated with worse performance on a test of cognitive ability over time. Conclusion Urine neopterin may have potential as a biomarker for memory decline in Down syndrome, and could potentially also help to track progression of mild cognitive impairment (MCI) to Alzheimer’s disease in other high risk populations. [ABSTRACT FROM AUTHOR]

Objective: Atrioventricular septal defect is associated with a high risk of a chromosomal abnormality, particularly trisomy 21. The aim of this study is to assess the rate of trisomy 21 in fetuses diagnosed with an atrioventricular septal defect and to examine the influence of prior screening on the rate of trisomy 21.Methods: Electronic ultrasound database was searched to identify fetuses diagnoses with an atrioventricular septal defect from 2002 to 2014. Rate of trisomy 21 and other aneuploidies was calculated among fetuses with normal situs. The prevalence of trisomy 21 and other aneuploidies was assessed in women with low and high first trimester risk for trisomy 21, using a cut-off value of 1:150 and 1:250.Results: A total 110 fetuses with a diagnosis of atrioventricular septal defect were identified. Among the 98 fetuses with normal situs, the prevalence of trisomy 21 was 46% (95% CI: 36-56%). Using a 1:150 threshold, the rate of trisomy 21 within the low-risk group was 41% (95% CI: 27-57%) while in the high-risk group it was 70% (95% CI: 52-83%), significantly higher than in the low risk group (p=0.028). Similar results were obtained when the 1:250 threshold was applied (66% versus 41%, p=0.055).Conclusions: The rate of trisomy 21 among fetuses identified with an atrioventricular septal defect in the second trimester is high even in those that undergo first trimester combined screening. Some fetuses with a high-risk screening result show a normal karyotype. Therefore, an offer of an invasive procedure to check fetal karyotyping is indicated. Knowledge of these rates may be helpful for parents in the decision making process. [ABSTRACT FROM AUTHOR]

The experimental research presented in this paper reports on findings from the study of case (syntactic and morphological) in 16 Cypriot Greek adults diagnosed with Down syndrome (DS) and 17 typically developing children. We perform phonetic and phonological analyses alongside morphosyntactic and syntactic analyses on data collected from eight experimental tasks. Results reveal near-ceiling performance for both groups. Syntactically conditioned differences related to structural complexity, problematic use of tense and subject-verb agreement or bundling/DP effects, are not recorded. We establish that the greater majority of differences observed between the two groups are mainly conditioned by articulatory limitations related to the distinct physiology associated with DS, as well as minor differences in their phonological systems. A small residue of differences that are determined to be morphosyntactic in nature is also recorded; these exhibit a clear systematicity in choosing the default case value (nominative), instead of the targeted one. Given the close to ceiling performance with case, morphosyntactic inaccuracies are determined to be neither due to lack of knowledge of the case assignment mechanisms, nor lack of knowledge of inflectional paradigms, but rather a morphological discrepancy, during the Vocabulary Insertion stage. [ABSTRACT FROM AUTHOR]

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Background: Children with Down syndrome (DS) are vulnerable to obstructive sleep apnoea (OSA) because of their unique craniofacial anatomy and hypotonia. Understanding the predictors of OSA in DS may enable targeted screening.Methods: Children with DS (n = 202) aged from six months to below six years (110 boys) were recruited from three UK children's hospitals. The clinical assessment included height, weight and tonsillar size. The parents either set up cardiorespiratory polygraphy at home or chose laboratory studies. Studies with less than four hours of interpretable data were repeated where possible. American Academy of Sleep Medicine (AASM) 2012 scoring criteria were used to derive an obstructive apnoea/hypopnoea index (OAHI). Predictors of moderate to severe OSA were examined.Results: In total, 188/202 (93%) participants were successfully studied. Of these, 169 studies were completed at home and 19 in a sleep laboratory. Moderate to severe OSA, defined by an OAHI of >5/h, was found in 14% and mild to moderate OSA (1/h≥OAHI <5/h) was found in 59% of the children. Male gender and habitual snoring predicted OSA but did not have independent predictive power in the presence of the other factors. Age in months, body mass index (BMI) centile and tonsillar size did not predict OSA.Conclusions: Moderate to severe OSA is common in very young children with DS. Examination of tonsillar size did not predict OSA severity. Population-based screening for OSA is recommended in these children, and domiciliary cardiorespiratory polygraphy is an acceptable screening approach. Further research is required to understand the natural history, associated morbidity, optimal screening methodology and treatment modality for OSA in these children. [ABSTRACT FROM AUTHOR]

Objective: To determine if human immunodeficiency virus (HIV) infection or antiretroviral therapy interferes with maternal levels of free human β-chorionic gonadotrophin (hCGβ) and pregnancy-associated plasma protein-A (PAPP-A) and whether any such influence alters first-trimester Down syndrome (DS) screening in HIV-infected women.Study Design: We performed a multicenter 1:2 matched case-control study comparing 84 HIV-infected women with singleton pregnancies with controls randomly selected among uninfected women, delivered and screened in the same center and matched for maternal age, geographical origin and fetal sex.Results: Groups did not differ significantly in screening results, although case women showed a slightly lower median free hCGβ multiple of the median (MoM) (1.11 versus 1.24 MoM, p=0.32) and higher median PAPP-A MoM (1.45 versus 1.32 MoM, p=0.23) than control women. The false-positive rate was similar in the case and control groups (5% versus 6.5%, p=0.5). Biomarker levels did not differ when comparing treated and untreated patients with their respective controls, and with one another.Conclusion: First-trimester DS combined screening biomarker levels and calculated risk do not seem to be significantly altered by HIV infection or antiretroviral treatment. This screening strategy appears to be suitable for HIV-infected women. [ABSTRACT FROM AUTHOR]

Objectives Results of epidemiological studies of lipid profiles in individuals with Down Syndrome (DS) in different settings showed discordant results but laboratory norms for this population has been lacking. The aim of our study is to evaluate lipid profiles in a large population of Italian children with DS. Methods Lipid profiles of 357 patients with diagnosis of DS were recorded. RESULTS: Multiple linear regression was employed to estimate models for each lipid fraction as a function of sex and age in patients with DS. Conclusions The main contribution of this paper is to provide data about lipid profile on a large cohort of people with Down syndrome. Long-term surveillance will be crucial to establish if this specific lipid profile may translate into increased morbidity and mortality from cardiovascular diseases (CVD) [ABSTRACT FROM AUTHOR]

We use a 1993 policy change in Israel's public healthcare system that lowered the eligibility age for amniocentesis to 35 to study the effects of financing of screening tests. Financing is found to have increased amniocentesis testing by about 35%. At ages above the eligibility threshold, utilization rates rose to roughly 33%, reflection nearly full takeup among prospective users of amniocentesis. Additionally, whereas below the age-35 threshold amniocentesis utilization rates increase with maternal age, this relation is muted above this age. Finally, no evidence is found that financing affects outcomes such as pregnancy terminations and births of children with Down syndrome. These results support the view that women above the eligibility threshold tend to refrain from acquiring inexpensive information about their degree of risk that absent the financing they would acquire, and instead, undergo the accurate and costly test regardless of additional information that noninvasive screening would provide. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the potential of maternal serum placental growth factor (PlGF) as a marker for Trisomy 21 in Chinese pregnant women.Study Design: Serum samples were collected and stored from 600 women who have a viable singleton pregnancy and underwent first trimester screening for Trisomy 21 between 2011 and 2014. Serum concentration of PlGF was measured using the automated time-solved immunofluorometric assay and expressed as Multiples of the expected median (MoM) from the 600 women available stored serum samples (558 Euploidy and 42 Trisomy 21). The levels of PlGF MoM were compared between Trisomy 21 cases and Euploid pregnancies. Expected median PlGF levels in Chinese were also compared to that published for Caucasians. Multivariate Gaussian modeling was performed to predict detection and false-positive rates.Results: In euploid pregnancies the concentrations of PlGF increased with Crown Rump Length(CRL) and decreased with maternal weight. The overall median MoM of PlGF in Chinese was higher than that of Caucasian. The median PlGF level was 0.63 MoM in the cases and 1.00 MoM in the controls (p<0.0001). The prediction of Trisomy 21 has been slightly improved by the addition of PlGF to the standard screening test in China. The detection rate of screening after adding PlGF data was increased from 93.4% to 94.6% at a false-positive rate of 3% and the false positive rate decreased from 0.23% to 0.17% for a detection rate of 80%.Conclusion: The median PlGF concentrations in Chinese is higher than those of Caucasians. Results suggest adding PlGF may substantially improve the performance of current first trimester screening strategy for Trisomy 21 in Chinese pregnant women. [ABSTRACT FROM AUTHOR]

Objective: Non-invasive prenatal testing (NIPT) is increasingly being used in prenatal aneuploidy screening. The objective of this study was to assess the positive predictive value in our cohort of 68 cases with positive NIPT result. In addition, we wondered if the use of NIPT in cases with ultrasound abnormalities is appropriate, given the limited number of chromosomes investigated.Design: We performed confirmative invasive testing using karyotyping, fluorescence in situ hybridization (FISH) and/or high-resolution chromosomal microarray analysis.Results: In line with the published data, the positive NIPT result was confirmed in 64.7% of cases. Inconclusive and negative NIPT results followed by cytogenetically pathologic findings were encountered in three and in five cases, respectively. Four of the five fetuses with negative NIPT but pathologic cytogenetic findings were born with several malformations and diagnosed right after birth with severe genetic conditions. Of note, in all of those four cases, NIPT was offered despite the finding of major fetal ultrasound abnormalities and despite the fact that the family would not have opposed invasive testing or pregnancy termination.Conclusion: More education of health care providers and caution in counseling and interpretation of test results are needed in order to meet the challenges that this new test, which enriches our diagnostic options in prenatal testing, poses. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical value of prenatal diagnosis of fetuses with increased nuchal translucency (NT) using an approach based on quantitative fluorescent polymerase chain reaction (QF-PCR) and chromosomal microarray (CMA).Study Design: From January 2013 to October 2014, we included 175 pregnancies with fetal NT ≥ 3.5mm at 11-13 weeks' gestation who received chorionic villus sampling. QF-PCR was first used to rapidly detect common aneuploidies. The cases with a normal QF-PCR result were analyzed by CMA.Results: Of the 175 cases, common aneuploidies were detected by QF-PCR in 53 (30.2%) cases (30 cases of trisomy 21, 12 cases of monosomy X, 7 cases of trisomy 18, 3 cases of trisomy 13 and 1 case of 47, XXY). Among the 122 cases with a normal QF-PCR result, microarray detected additional pathogenic copy number variants (CNVs) in 5.7% (7/122) of cases. Four cases would have expected to be detectable by conventional karyotyping because of large deletions/duplications (>10 Mb), leaving three cases (2.5%; 3/118) with pathogenic CNVs only detectable by CMA.Conclusion: It is rational to use a diagnostic strategy in which CMA is preceded by the less expensive, rapid, QF-PCR to detect common aneuploidies. CMA allows detection of a number of pathogenic chromosomal aberrations in fetuses with a high NT. [ABSTRACT FROM AUTHOR]

Background/aim: To determine whether there are specific characteristic intrapartum heart rate patterns for fetuses with trisomy 21(T21).Background Study Design/patients: Intrapartum fetal heart rate (FHR) tracings of T21 fetuses were compared to those of euploid fetuses in a retrospective, observational, matched, case-control study. The study group consisted of 42 fetuses with T21 and 42 matched euploid controls. Matching was designed to accommodate possible confounders. The sign test and McNemar's test were used for categorical variables. The paired t test was used for comparison between quantitative variables.Results: Intrapartum baseline FHR of fetuses with T21 was found to be slightly decreased compared to controls (122.5 vs 129.05 beats per minute, p=0.028). No differences were detected in the presence of periodic changes, or FHR variability between the groups.Conclusion: When evaluating intrapartum FHR of fetuses with T21, decreased baseline FHR can be expected. [ABSTRACT FROM AUTHOR]

This study aimed to investigate obstacle crossing in 7-9-year-old children with Down syndrome (DS). Fifteen children with DS, age- and gender-matched with 15 typically developing (TD) children, were recruited to walk and cross obstacles with heights of 10%, 20% and 30% of their leg lengths. End-point and kinematic variables of obstacle crossing were obtained using a three-dimensional motion analysis system. The results showed that children with DS tend to adopt a lower speed and larger step width when they perceive instability. Moreover, unlike TD children, children with DS adopt a pelvic strategy (i.e., greater pelvic leading-side listing and forward rotation) to achieve a higher leading toe clearance with a longer step length, presumably for safety reasons. This pelvic strategy increased the frontal plane motion of the whole leg and trunk, and thus possibly stability, during obstacle crossing. However, this strategy may be inefficient. Trailing toe clearance did not differ significantly between two groups. The results of this study suggest that children with DS tend to use inefficient and conservative strategies for obstacle crossing. Knowledge of both end-point and kinematic control of obstacle crossing in children with DS is useful for understanding the mechanisms of obstacle-related falls. Moreover, obstacle crossing can be used as a task-oriented rehabilitation program for children with DS. [ABSTRACT FROM AUTHOR]

Aim: The purpose of the study was to explore the test-retest reliability and minimal detectable change of selected functional fitness test items in adults with Down syndrome.Methods: Forty-three adults with Down syndrome (24 men and 19 women) aged 18-50 years completed a battery of tests twice in a two-week period. The battery of tests consisted of two balance items, two flexibility items, five muscular strength and endurance items, two aerobic items, and one functional task. All items were considered valid and reliable tests in a general elderly or intellectually disabled population. The test-retest relative reliability for all repeated tests was assessed with intraclass correlation coefficient performing one-way analysis of variance. The test-retest absolute variability was measured by using the standard error of measurement (SEM) to calculate the minimal detectable change at the 90% confidence interval (MDC90). Reliability data was visualised with a Bland-Altman plot.Results: All tests showed excellent intraclass correlation coefficients (ICC's>0.9). All SEM values demonstrated acceptable measurement precision (SEMConclusion: All twelve functional fitness tests demonstrated adequate feasibility and relative and absolute test-retest reliability in adults with Down syndrome in South Africa. Information of this nature will help to monitor performance alterations over time and success of training interventions. [ABSTRACT FROM AUTHOR]

Background: Cell-free DNA noninvasive prenatal screening for trisomies 21, 18, and 13 has been rapidly adopted into clinical practice. However, previous studies are limited by a lack of follow-up genetic testing to confirm the outcomes and accurately assess test performance, particularly in women at a low risk for aneuploidy.Objective: To measure and compare the performance of cell-free DNA screening for trisomies 21, 18, and 13 between women at a low and high risk for aneuploidy in a large, prospective cohort with genetic confirmation of results STUDY DESIGN: This was a multicenter prospective observational study at 21 centers in 6 countries. Women who had single-nucleotide-polymorphism-based cell-free DNA screening for trisomies 21, 18, and 13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. The test performance and test failure (no-call) rates were assessed for the cohort, and women with low and high previous risks for aneuploidy were compared. An updated cell-free DNA algorithm blinded to the pregnancy outcome was also assessed.Results: A total of 20,194 women were enrolled at a median gestational age of 12.6 weeks (interquartile range, 11.6-13.9). The genetic outcomes were confirmed in 17,851 cases (88.4%): 13,043 (73.1%) low-risk and 4808 (26.9%) high-risk cases for aneuploidy. Overall, 133 trisomies were diagnosed (100 trisomy 21; 18 trisomy 18; 15 trisomy 13). The cell-free DNA screen positive rate was lower in the low-risk vs the high-risk group (0.27% vs 2.2%; P<.0001). The sensitivity and specificity were similar between the groups. The positive predictive value for the low- and high-risk groups was 85.7% vs 97.5%; P=.058 for trisomy 21; 50.0% vs 81.3%; P=.283 for trisomy 18; and 62.5% vs 83.3; P=.58 for trisomy 13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. The trisomy rate was higher in the 287 cases with no-call results than patients with a result on a first draw (2.8% vs 0.7%; P=.001). The updated algorithm showed similar sensitivity and specificity to the study algorithm with a lower no-call rate.Conclusion: In women at a low risk for aneuploidy, single-nucleotide-polymorphism-based cell-free DNA has high sensitivity and specificity, positive predictive value of 85.7% for trisomy 21 and 74.3% for the 3 common trisomies. Patients who receive a no-call result are at an increased risk of aneuploidy and require additional investigation. [ABSTRACT FROM AUTHOR]

Objectives To quantify palatal bone thickness (PBT) in Down's syndrome (DS) patients in order to identify the best areas for miniscrew placement. Design The study group was formed of 40 DS patients (25 male and 15 female) with a mean age of 18.4 ± 6.3 years (range, 9–40 years). A control group of 40 non-syndromic age- and sex-matched individuals was selected. Maxillary CBCT images were available for all participants. Coronal sections of the hard palate were selected at 4, 8, 16 and 24 mm posterior to the distal wall of the incisive foramen. PBT measurements were performed at 20 selected points on these coronal sections at the midline and at 3 and 6 mm to right and left of the suture. Results Overall, PBT was similar in DS and controls and it was not affected by age or sex. In both groups PBT decreased progressively with increasing distance from the posterior wall of the nasopalatine foramen in an anteroposterior direction, except along the median palatal suture. PBT along the suture was lower in DS than in controls in all the paracoronal image planes ( P = 0.02, 0.007, 0.01 and 0.02 at 4 mm, 8 mm, 16 mm and 24 mm, respectively, from the incisive foramen). PBT at the most anterior paramedian locations was also lower in DS than in controls ( P = 0.02 and 0.03, respectively, 3 mm to the right and left of midline). Conclusions In DS individuals, the most suitable area for miniscrew placement in terms of bone volume is the median palatal suture, irrespective of age or sex, as occurs in the general population, followed by the paramedian sites closest to the incisive foramen. [ABSTRACT FROM AUTHOR]

Writing is a complex task that requires the integration of multiple cognitive, linguistic, and motor abilities. Until now, only a few studies investigated writing abilities in individuals with Intellectual Disability (ID). The aim of the present exploratory study was to provide knowledge on the organization of writing in two populations with ID, Down syndrome (DS) and Williams syndrome (WS), trying to disentangle different components of the process. A battery tapping diverse writing demands as low-level transcription skills as well as high-level writing skills was proposed to 13 individuals with WS, 12 individuals with DS and 11 mental-age-matched typically developing (TD) children. Results showed that the two groups with genetic syndromes did not differ from TD in writing a list of objects placed in bedroom, in the number of errors in the text composition, in a text copying task and in kind of errors made. However, in a word dictation task, individuals with DS made more errors than individuals with WS and TD children. In a pseudoword dictation task, both individuals with DS and WS showed more errors than TD children. Our results showed good abilities in individuals with ID in different aspects of writing, involving not only low-level transcription skills but also high-level composition skills. Contrary to the pessimistic view, considering individuals with ID vulnerable for failure, our results indicate that the presence of ID does not prevent the achievement of writing skills. [ABSTRACT FROM AUTHOR]

This study aims to answer the research question of "Are early onset aging conditions correlated to daily activity functions in youth and adults with Down syndrome (DS)?" A cross-sectional survey was employed to recruit 216 individuals with DS over 15 years of age in the analyses. A structured questionnaire included demographic data, brief self-reported aging conditions, Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) and activity of daily living (ADL) scales were completed by the primary caregivers who were well-suited for providing information on the functioning conditions of the DS individuals. Results showed that the most five frequent aging conditions (sometimes, usually and always) included frailty (20.2%), vision problem (15.8%), loss of language ability (15.3%), sleep problem (14.9%) and memory impairment (14.5%). Other onset aging conditions included more chronic diseases (13.9%), hearing loss (13%), chewing ability and tooth loss (12.5%), incontinence (11.1%), depressive syndrome (7.7%), falls and gait disorder (7.2%), loss of taste and smell (7.2%). The data also showed scores of DSQIID, onset aging conditions and ADL has significant relationships each other in Pearson's correlation tests. Finally, multiple linear regression analyses indicated onset aging conditions (β=-0.735, p<0.001) can significantly predicted the variation in ADL scores after adjusting other factors (R2=0.381). This study suggests that the authority should initiate early intervention programs aim to improve healthy aging and ADL functions for people with DS. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The prevalence of epilepsy in patients with Down syndrome (DS) is 5–13%, which is higher than the prevalence in the general population. Transient hyperammonemia is often observed following seizure, but it typically resolves within a day. Here, we describe the case a 37-year-old woman who had DS and a history of adult-onset epilepsy and was admitted to our hospital with recurrent seizures. After admission, her ammonia levels fluctuated without any apparent cause, and dynamic computed tomography revealed a portosystemic shunt. The findings suggest that her seizures possibly precipitated from hyperammonemia secondary to a portosystemic shunt, and we reviewed the relevant literature. Methods: We conducted PubMed, Web of Science, and EMBASE searches without language restrictions for articles published between 1970 and February 2013. Results: In addition to the present case, 7 cases were ultimately included in this review. Four patients were newborns, 2 patients were 1month old, and 1 patient was 3years old. No adult cases were described until now. Conclusion: Adult patients with DS diagnosed with epilepsy are not routinely assessed for portosystemic venous shunts. Measuring ammonia levels in patients with DS the day after admission would help detect portosystemic shunts, even if the patients have been previously diagnosed with epilepsy. Practice Implications: If ammonia levels fluctuate without any apparent cause after seizure, dynamic computed tomography should be performed, especially for patients with DS, whether or not they have been previously diagnosed with epilepsy. [Copyright &y& Elsevier]

Down syndrome, trisomy 21, is the most common autosomal trisomy, and commonest identifiable cause of learning disability. Despite current prenatal screening practice birth prevalence continues to be around 1/1000 live births. Children with Down syndrome have an increased risk of congenital abnormalities and a wide range of treatable medical problems. Paediatricians have a key role in ensuring that these are recognized and treated so that the children's progress is not hampered by additional secondary but preventable disability, and health problems do not prevent them reaching their potential. In this article we consider the Paediatrician's role with a suggested approach to medical management throughout childhood, and a review of the most frequently occurring health issues. These include cardiac, respiratory, gastrointestinal and haematological disorders, thyroid dysfunction, hearing and vision problems, cervical spine and other orthopaedic problems, immune and autistic spectrum disorders, growth and sexual development. [ABSTRACT FROM AUTHOR]

Abstract: Down syndrome (DS) is the most frequent genetic cause of intellectual disability characterized by the presence of three copies of chromosome 21 (Chr21). Individuals with DS have sufficient neuropathology for a diagnosis of Alzheimer's disease (AD) after the age of 40years. The aim of our study is to gain new insights in the molecular mechanisms impaired in DS subjects that eventually lead to the development of dementia. We evaluate the PI3K/Akt/mTOR axis in the frontal cortex from DS cases (under the age of 40years) and DS with AD neuropathology compared with age-matched controls (Young and Old). The PI3K/Akt/mTOR axis may control several key pathways involved in AD that, if aberrantly regulated, affect amyloid beta (Aβ) deposition and tau phosphorylation. Our results show a hyperactivation of PI3K/Akt/mTOR axis in individuals with DS, with and without AD pathology, in comparison with respective controls. The PI3K/Akt/mTOR deregulation results in decreased autophagy, inhibition of IRS1 and GSK3β activity. Moreover, our data suggest that aberrant activation of the PI3K/Akt/mTOR axis acts in parallel to RCAN1 in phosphorylating tau, in DS and DS/AD. In conclusion, this study provides insights into the neuropathological mechanisms that may be engaged during the development of AD in DS. We suggest that deregulation of this signaling cascade is already evident in young DS cases and persist in the presence of AD pathology. The impairment of the PI3K/Akt/mTOR axis in DS population might represent a key-contributing factor to the neurodegenerative process that culminates in Alzheimer-like dementia. [Copyright &y& Elsevier]

Abstract: Objective: Down Syndrome (DS) is the most common chromosome abnormality in liveborn children. Otolaryngologists frequently encounter these patients in their practice; in one survey, 50% of DS patients had been seen by Otolaryngology at least once. As such, it is essential that the practicing Otolaryngologist is aware of the otologic, rhinologic, and laryngologic manifestations of this complex disease and comfortable in the management and treatment of these unique patients. Our goal was to provide this information in a concise and definitive document. Methods: A comprehensive literature review using PubMed was completed. The terms “Otolaryngology”, “Head and neck”, “Ear, nose, throat”, “Down Syndrome”, and “Trisomy 21” were searched in various combinations. Applicable articles that discussed the Otolaryngologic manifestations of Down Syndrome were included. Results: In total, fifty articles were included for review. The Down Syndrome child tends to have smaller external ear canals, have higher rates of chronic ear disease, and may present with conductive, sensorineural, or mixed hearing loss. As such, DS patients should receive behaviouralaudiological testing every 6 monthsand annually after the age of three in addition to closer follow-up by an Otolaryngologist if tympanic membranes cannot be visualized or if the external auditory canals are significantly stenosed. Management should involve close follow-up and a low threshold for PE tube placement to reduce the risks for speech and language delay. Chronic rhinitis in the Down Syndrome patient is common. Retrognathia, hypotonia, and macroglossia can all cause obstructive sleep apnea (OSA) in this population and therefore each DS patient should get an overnight polysomnograph. Subglottic stenosis, vocal cord paralysis and laryngomalacia are not infrequently seen in the Down Syndrome patient. To reduce acquired subglottic stenosis, endotracheal tubes that are at least two sizes smaller than what is appropriate for the patient's age should be used. Conclusion: Down Syndrome is common and there are many Otolaryngologic manifestations. We recommend that this patient population visit an Otolaryngologist on a regular basis and that the practicing Otolaryngologist is comfortable with the management and treatment of the unique challenges faced with these children. [Copyright &y& Elsevier]

Highlights: [•] Down syndrome is associated with systemic oxidative stress. [•] Antioxidant intervention attenuates oxidative stress in children with Down syndrome. [•] Antioxidant supplementation attenuates the oxidative damage in Down syndrome patients. [•] Vitamins E and C therapy improves antioxidant status in Down syndrome children's blood. [•] Vitamin supplementation restored glutathione depletion in Down syndrome children. [Copyright &y& Elsevier]

Highlights: [•] Individuals with DS learn to read new words at a level equal to their decoding skill. [•] This is below the level of their existing word reading skill. [•] They can apply phonological knowledge when reading novel words. [•] This is to the same extent as in typical development when matched on baseline decoding. [•] Hearing new words first may help children to read them. [ABSTRACT FROM AUTHOR]

Abstract: In industrialised countries, certain biomedical innovations have come into general use, but the ways they are used vary considerably. Prenatal screening techniques for Down's syndrome are a perfect example of this. In 2010, screening rates stood at 61% in England and 84% in France; the previous year the rate was 26% in the Netherlands. The objective of our research, which took place in these three countries between 2008 and 2011, was to explain these differences. In these countries, public authorities focus on women's free access to innovations and on receiving their informed consent. But other aspects of screening policy vary, as do the health systems in which they are implemented. Our study shows that the sociotechnical settings which vary from country to country affected the interactions during the consultations we observed and thus impacted the decision of whether or not to screen. [Copyright &y& Elsevier]

Abstract: Although there is a long list of syndromes with phocomelia, there are only two syndromes in which there is concurrent pelvic dysplasia and phocomelia: Al-Awadi–Raas-Rothschild syndrome (AARRS) and Schinzel phocomelia syndrome (SPS). Currently, there is a diagnostic confusion between the two syndromes and both have the same MIM entry (MIM 276820). We believe that the two syndromes are different entities and we also believe that the limb defect in SPS is a “true” phocomelia while the limb defect in AARRS is an “apparent” phocomelia. “Apparent” phocomelia describes the most severe form of ulnar ray deficiency in which there is absent ulna with radio-humeral synostosis. “Apparent” phocomelia is diagnosed radiologically by three radiological features: the apparently single bone occupying the arm/forearm appears relatively long, the area of radio-humeral synostosis will have thicker cortex with or without slight angulation, and the lower end of the bone resembles the lower end of a radius and not a humerus. In this paper, we present two new cases of AARRS from two different Saudi Arabian tribes: one case with R292C mutation of WNT7A with bilateral “apparent” phocomelia and a second case with a novel c.814G>T mutation of the WNT7A gene (resulting in wnt7a protein truncation at position 272) with unilateral “apparent” phocomelia. We reviewed previously reported cases of AARRS and SPS to further delineate the differences between these two syndromes. We make the argument that these two syndromes are two different entities and hence require two different MIM entries. [Copyright &y& Elsevier]

Abstract: DS is the most frequent genetic cause of intellectual disability characterized by the anomalous presence of three copies of chromosome 21. One of the peculiar features of DS is the onset of Alzheimer's disease neuropathology after the age of 40years characterized by deposition of senile plaques and neurofibrillary tangles. Growing studies demonstrated that increased oxidative damage, accumulation of unfolded/damaged protein aggregates and dysfunction of intracellular degradative system are key players in neurodegenerative processes. In this study, redox proteomics approach was used to analyze the frontal cortex from DS subjects under the age of 40 compared with age-matched controls, and proteins found to be increasingly carbonylated were identified. Interestingly, our results showed that oxidative damage targets specifically different components of the intracellular quality control system such as GRP78, UCH-L1, V0-ATPase, cathepsin D and GFAP that couples with decreased activity of the proteasome and autophagosome formation observed. We also reported a slight but consistent increase of Aβ 1–42 SDS- and PBS-soluble form and tau phosphorylation in DS versus CTR. We suggest that disturbance in the proteostasis network could contribute to the accumulation of protein aggregates, such as amyloid deposits and NFTs, which occur very early in DS. It is likely that a sub-optimal functioning of degradative systems occur in DS neurons, which in turn provide the basis for further accumulation of toxic protein aggregates. The results of this study suggest that oxidation of protein members of the proteostatis network is an early event in DS and might contribute to neurodegenerative phenomena. [Copyright &y& Elsevier]

Purpose: To measure corneal thickness via the use of a Scheimpflug imaging system (OCULUS Optikgeräte GmbH, Wetzlar, Germany) in children with Down syndrome. Methods: This prospective, nonrandomized, clinical trial included children with Down syndrome and age- and sex-matched healthy controls. All subjects received a complete ophthalmologic examination. Corneal topography measurements were acquired by means of Scheimpflug imaging. Central corneal thickness (CCT), thinnest point of cornea (TP), and corneal volume (CV) were analyzed. Results: A total of 27 children with Down syndrome and 37 control subjects were included in the study. In children with Down syndrome, the mean CCT was 494.27 ± 47 μm, the mean TP was 487 ± 49 μm, and the mean CV was 56.2 ± 6. In the controls, the mean CCT was 539.3 ± 40 μm, the mean TP was 538.0 ± 40.8 μm, and the mean CV was 61.3 ± 4. For all 3 parameters, the difference was statistically significant (P < 0.001). In the Down syndrome group, the CCT was <500 μm in 16 subjects (59.2%) and <450 μm in 5 (18.5%). In the control group, the CCT was <500 μm in 14 subjects (37.8%) and <450 μm in 2 (5.4%). Conclusions: In this study, corneal thickness was less in children with Down syndrome than in healthy control subjects. Decreased corneal thickness may be an early sign of a degenerative corneal disease such as keratoconus in children with Down syndrome. [ABSTRACT FROM AUTHOR]

Gingival bleeding is a relatively uncommon chief complaint in the pediatric population. The differential diagnosis is broad, and both the patient's clinical presentation and medical history must be taken into account when formulating a differential diagnosis. The following is a case of a child with trisomy 21 who presented to the emergency department with oral bleeding in the setting of a normal complete blood count and coagulation studies. The patient underwent a workup for coagulopathies, malignancy, and nutritional deficiencies and was found to have vitamin C deficiency, also known as scurvy. This case illustrates a rare cause of gingival bleeding that occurs primarily in developing countries but may also occur in developed countries in children with underlying medical conditions such trisomy 21 or developmental delay. [ABSTRACT FROM AUTHOR]

Abstract: During the last decade, the area of non-invasive prenatal diagnosis (NIPD) has rapidly evolved. Several methodological approaches have been presented and demonstrated a proof of concept for the NIPD of chromosomal aneuploidies. The two most promising methods are NIPD using next generation sequencing technologies and NIPD using Methylation DNA Immunoprecipitation (MeDIP) with real time qPCR. Both approaches have been validated with blind studies and have >99% accuracy. NIPD using next generation sequencing is achieved by high throughput shotgun sequencing of DNA from plasma of maternal women followed by ratio comparisons of each chromosome sequence tag density over the median tag density of all autosomes (z-score analysis). The MeDIP real time qPCR method, which is described in this review in more detail, is based on the identification of differentially methylated regions (DMRs) and their use in discriminating normal from abnormal cases. More than 10,000 DMRs were identified for chromosomes 13, 18, 21, X and Y using high resolution oligo-arrays that can be potentially used for the NIPD of aneuploidies for chromosomes 13, 18, 21, X and Y. Both NIPD methods have several advantages and limitations and it is believed that they will soon be implemented in clinical practice. With the continuous advancements of genetic methodologies and technologies, we predict that within the next 10years we will be able to provide NIPD for all common and rare genetic disorders where the molecular basis is known. [Copyright &y& Elsevier]