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IntroductionPeople with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials.MethodsThis large cross-sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (Aβ)42/40, total tau, and neurofilament light chain (NfL) and cognitive (episodic memory, visual-motor integration, and visuospatial abilities) and functional (adaptive behavior) impairments in 260 adults with DS without dementia (aged 25-81 years).ResultsIn general linear models lower plasma Aβ42/40 was related to lower visuospatial ability, higher total tau was related to lower episodic memory, and higher NfL was related to lower visuospatial ability and lower episodic memory.DiscussionPlasma biomarkers may have utility in tracking AD pathology associated with early stages of cognitive decline in adults with DS, although associations were modest.HighlightsPlasma Alzheimer's disease (AD) biomarkers correlate with cognition prior to dementia in Down syndrome.Lower plasma amyloid beta 42/40 was related to lower visuospatial abilities.Higher plasma total tau and neurofilament light chain were associated with lower cognitive performance.Plasma biomarkers show potential for tracking early stages of AD symptomology.

Objectives Our objective was to investigate the prevalence of small intestinal atresia and Hirschsprung's disease (HD) in infants with Down syndrome (DS) and its impact on outcomes. Study Design We analyzed the National Inpatient Sample dataset. We included infants with DS, small intestinal atresia, HD, and the concomitant occurrence of both conditions. Regression analysis was used to control clinical and demographic variables. Results A total of 66,213,034 infants were included, of whom, 99,861 (0.15%) had DS. The concomitant occurrence of small intestinal atresia and HD was more frequent in infants with DS compared with the general population, adjusted odds ratio (aOR): 122, 95% confidence interval (CI): 96–154, (p < 0.001). Infants with DS and concomitant small intestinal atresia and HD had higher mortality compared with those without these conditions, aOR: 8.59, 95% CI: 1.95–37.8. Conclusion Infants with DS are at increased risk of concomitant small intestinal atresia and HD, and this condition is associated with increased mortality. Key Points Infants with Down syndrome are at increased risk of congenital GI anomalies. Infants with Down syndrome are at increased risk of necrotizing enterocolitis. Increased mortality in Down syndrome infants with concomitant small intestinal atresia and Hirschsprung's disease. [ABSTRACT FROM AUTHOR]

• VGB effectiveness for IESS was evaluated based on etiology excluding TSC. • Overall effectiveness of VGB for IESS with variable etiologies was 39.0 % (16/41 cases). • VGB effectiveness for congenital structural diseases was 9.1 % (1/11 cases). • Alternative treatments should be considered for congenital structural diseases. We aimed to assess the effectiveness of vigabatrin (VGB) in patients diagnosed with infantile epileptic spasm syndrome (IESS) and categorize these patients based on their etiologies. This retrospective study included patients diagnosed with IESS who exhibited epileptic spasms before the age of 2 years between January 1, 2015, and October 31, 2023 at Saitama Children's Medical Center. Patients with tuberous sclerosis as the identified etiology were excluded. The effectiveness of VGB was assessed based on the resolution of ES for three months with the absence of hypsarrhythmia on interictal electroencephalogram. This study analyzed 41 patients (26 boys). The etiologies included genetic, congenital structural, acquired structural, and unknown in 12, 11, 10, and 8 patients, respectively. Patient characteristics did not significantly differ among the four groups. The overall effectiveness of VGB for IESS was 39.0 % (16/41). Categorized based on etiology, VGB was effective in 41.7 % (5/12), 9.1 % (1/11), 50 % (5/10), and 75 % (6/8) in the genetic, congenital structural, acquired structural, and unknown groups, respectively. Statistical analysis revealed a significant difference in effectiveness among the four groups (p = 0.03). Categorized based on diseases, VGB was effective in 28.6 % (2/7) and 50 % (4/8) in trisomy 21 and perinatal brain injury, respectively. The effectiveness of VGB in patients with IESS varied with etiology. Further investigations into the effectiveness of VGB in etiological subtypes of IESS could facilitate the development of tailored treatment algorithms for each etiology, representing valuable guidelines for future medical practice. [ABSTRACT FROM AUTHOR]

Both arteriovenous malformation (AVM) and trisomy 21 are rare diseases. Studies have shown that individuals with trisomy 21 may have potential vascular malformations, with the main site of onset being the portal system. This case involved an adult patient with trisomy 21 who presented with pelvic iliac arteriovenous malformations. The patient underwent interventional treatment, and the prognosis was favorable. It is important to enhance the screening for vascular malformations in patients with trisomy 21 syndrome. At the same time, interventional treatment for AVMs is effective and increasingly important for managing AVMs. [ABSTRACT FROM AUTHOR]

Background: Down syndrome (DS), a common chromosomal anomaly caused by trisomy of chromosome 21, is characterized by a broad spectrum of phenotypic characteristics across multiple organ systems, including cardiac defects and leukemia. Dermatological findings are prevalent among individuals with DS; however, these issues are frequently underrecognized and inadequately researched, resulting in a significant gap in the provision of comprehensive healthcare strategies. Given the increased life expectancy of patients with DS and delayed manifestation of many dermatoses, physicians are increasingly encountering dermatological findings in this population. Objective: This study aimed to assess the prevalence and types of dermatological findings in individuals with DS, compare them with those in a control group, and emphasize the necessity of incorporating dermatological evaluations into routine health monitoring. Methods: This prospective cross‐sectional study was conducted from June 2023 to June 2024 and involved 100 genetically confirmed individuals with DS and 100 age‐ and sex‐matched controls. Comprehensive demographic, clinical, and karyotype data were collected for the DS group, and all the participants underwent detailed morphological evaluations. Results: The DS group had a mean age of approximately 6.37 years, whereas the controls were around 7 years old, with no significant differences in age or sex distribution between the groups. Karyotype analysis showed that trisomy 21 was present in 92% of the cases, mosaicism in 6%, and translocation in 2%. Common dermatological findings in the DS group included xerosis cutis (49%), thin and sparse hair (48%), dental caries (34%), delayed tooth eruption (28%), nail dystrophy (25%), fissured tongue (23%), and cheilitis (18%). Significant differences were noted in the prevalence of scabies, bacterial infections, and café au lait macules between the DS and control groups (p < 0.01). Dysmorphic findings in the DS group included epicanthal folds (97%), upslanted palpebral fissures (97%), brachycephaly (91%), and single transverse palmar crease (89%). Significant gender differences were noted in the prevalence of brachycephaly and the sandal gap (p < 0.01). Conclusions: This study highlights the importance of regular dermatological care in enhancing the health management and quality of life of individuals with DS due to the prevalence and variability of dermatological conditions. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Introduction: Down syndrome, or trisomy 21, is the most diagnosed chromosomal abnormality and is associated with multiple orthopedic concerns, including scoliosis. We sought to examine the surgical treatment of scoliosis associated with Down syndrome with an emphasis on specific complications in this population. Methods: A retrospective review of 13 patients with Down syndrome who underwent surgical intervention for spinal deformity between 2000 and 2018 were identified. Postoperative complications were classified using the modified Clavien-Dindo-Sink system. Perioperative and final follow-up radiographic data were analyzed. Results: The mean age at surgery was 14.2 years (11–19) with a mean follow-up of 3.6 years (0.4–6.2) at the time of data collection. Seven (54%) patients had postoperative complications, all related to wound healing. Three patients (23%) had major complications (Clavien-Dindo-Sink grade ≥3). These included one deep surgical site infection, one hematoma, and one seroma, all requiring surgical drainage. Four additional patients (31%) had minor complications (Clavien-Dindo-Sink grade ≤2). Discussion: Surgical intervention for scoliosis in patients with Down syndrome is associated with high complication rates despite the use of more modern surgical techniques and implant types. Complications in this cohort primarily involved wound healing, whereas previous studies described high rates of postoperative implant failure, pseudoarthrosis, and significant curve progression, which were not experienced by the patients in this study. Although the etiology of wound-related complications is unknown, awareness of this risk may help surgeons optimize surgical technique, postoperative monitoring, and preoperative counseling of families. Level of Evidence: IV—single-institution retrospective case series. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of Down syndrome (DS) is approximately 1 per 1000 births and is influenced by increasing maternal age over the last few decades. DS is strongly associated with congenital heart defects (CHDs), especially atrioventricular septal defect (AVSD). Our objectives were to investigate the prevalence of live‐born infants with DS having a severe CHD in the Norwegian population over the last 20 years and compare outcomes in infants with AVSD with and without DS. Material and Methods: Information on all births from January 1, 2000 to December 31, 2019 was obtained from the Medical Birth Registry of Norway. We also obtained data on all infants with severe CHDs in Norway registered in Oslo University Hospital's Clinical Registry for Congenital Heart Defects during 2000–2019 and accessed individual‐level patient data from the electronic hospital records of selected cases. Infants with AVSD and DS were compared to infants with AVSD without chromosomal defects. Crude and adjusted odds ratios (ORs) of infant mortality and need for surgery during the first year of life, with associated 95% confidence intervals (CIs), were estimated by logistic regression. Results: A total of 1 177 926 infants were live‐born in Norway during the study period. Among these, 1456 (0.1%) had DS. The prevalence of infants with DS having a severe CHDs was relatively stable, with a mean of 17 cases per year. The most common CHD associated with DS was AVSD (44.4%). Infants with AVSD and DS were more likely to have cardiac intervention during their first year of life compared to infants with AVSD without chromosomal defects (adjusted OR [aOR]: 2.52; 95% CI 1.27, 4.98). However, we observed no difference in infant mortality during first year of life between the two groups (aOR: 1.08; 95% CI 0.43, 2.70). Conclusions: The prevalence of live‐born infants with severe CHDs and DS has been stable in Norway across 20 years. Infants with AVSD and DS did not have higher risk of mortality during their first year of life compared to infants with AVSD without chromosomal defects, despite a higher risk of operative intervention. [ABSTRACT FROM AUTHOR]

Background: Infants with Trisomy 21 are known to have increased incidence congenital anomalies including congenital heart diseases (CHD) and congenital gastrointestinal anomalies. It is not known if there are patterns of coexistence. Objectives: To examine the coexistence of CHD with various gastrointestinal anomalies in infants with Trisomy 21. Methods: We assessed a sample of infants with Trisomy 21 from the National Inpatient Sample (NIS), and its KID subversion, produced by the Healthcare Cost and Utilization Project for 2003–2015. We identified CHD using international classification of diseases version 9 (ICD9) and categorized them into four groups: left sided lesions, right sided lesions, conotruncal lesions, and shunt lesions. We identified small intestinal atresia and Hirschsprung disease with ICD9 codes. Results: The sample included 81,561 newborn infants diagnosed with Trisomy 21; 45% of them had CHD; 4.7% had small intestinal atresia, and 1.6% had Hirschsprung disease. All subcategories of CHD were associated with increased incidence of both small intestinal atresia and Hirschsprung disease, p value < 0.05 compared to infants with Trisomy 21 who did not have CHD. Conclusions: Among infants with Trisomy 21, the presence of CHD increased the odds of a concomitant congenital GI anomaly. [ABSTRACT FROM AUTHOR]

Background: Multiple marker screening is offered to pregnant individuals in many jurisdictions to screen for trisomies 21 and 18. On occasion, the result is 'double-positive'—a screening result that is unexpectedly positive for both aneuploidies. Although this occurs rarely, the paucity of available evidence about the outcomes of these pregnancies hinders patient counselling. This study aimed to investigate the association of double-positive results with preterm birth and other adverse perinatal outcomes. Methods: We conducted a population-based retrospective cohort study of pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, using province-wide perinatal registry data in Ontario, Canada. Pregnancies with double-positive screening results where trisomies 21 and 18 were ruled-out were compared to pregnancies with screen negative results for both aneuploidies. We used modified Poisson regression models with robust variance estimation to examine the association of double positive results with preterm birth and secondary outcomes. Results: From 429 540 pregnancies with multiple marker screening, 863 (0.2%) had a double-positive result; trisomies 21 and 18 were ruled out in 374 pregnancies, 203 of which resulted in a live birth. Among the pregnancies in the double-positive group resulting in a live birth, the risk of preterm birth was increased compared to pregnancies with a screen negative result: adjusted risk ratio (aRR) 2.6 (95%CI 2.0-3.6), adjusted risk difference (aRD) 10.5% (95%CI 5.4–15.7). In a sensitivity analysis excluding all diagnosed chromosomal abnormalities, the risk of preterm birth remained elevated to a similar degree: aRR 2.6 (95%CI 1.9–3.7), aRD 10.0% (95%CI 4.8–15.3). The risk of other adverse perinatal outcomes was also higher, including the risk of chromosomal abnormalities other than trisomies 21 and 18: aRR 81.1 (95%CI 69.4–94.8), aRD 34.0% (95%CI 29.2–38.8). Pregnancies with double-positive results were also less likely to result in a live birth, even when excluding all diagnosed chromosomal abnormalities; and at increased risk of adverse perinatal outcomes for those resulting in a live birth. Conclusion: Although rare, double-positive multiple marker screening results are associated with an increased risk of preterm birth and other adverse perinatal outcomes, even when excluding all identified chromosomal abnormalities. [ABSTRACT FROM AUTHOR]

Abstract Both arteriovenous malformation (AVM) and trisomy 21 are rare diseases. Studies have shown that individuals with trisomy 21 may have potential vascular malformations, with the main site of onset being the portal system. This case involved an adult patient with trisomy 21 who presented with pelvic iliac arteriovenous malformations. The patient underwent interventional treatment, and the prognosis was favorable. It is important to enhance the screening for vascular malformations in patients with trisomy 21 syndrome. At the same time, interventional treatment for AVMs is effective and increasingly important for managing AVMs.

This systematic review examined whether physical activity interventions improve health outcomes in adults with Down syndrome (DS). We searched PubMed, APA PsycInfo, SPORTDiscus, APA PsycARTICLES, and Psychology and Behavioral Sciences Collection using keywords related to DS and physical activity. We included 35 studies published in English since January 1, 1990. Modes of exercise training programs included aerobic exercise, strength training, combined aerobic and strength training, aquatic, sport and gaming, and aerobic and strength exercise interventions combined with health education. The evidence base indicates that aerobic and strength exercise training improve physical fitness variables including maximal oxygen uptake, maximal heart rate, upper and lower body strength, body weight, and body fat percentage. Sport and gaming interventions improve functional mobility, work task performance, and sport skill performance. We concluded that adults with DS can accrue health benefits from properly designed physical activity and exercise interventions. [ABSTRACT FROM AUTHOR]

Abstract Background Down syndrome (DS), or Trisomy 21, is defined by the existence of an additional chromosome 21. Various physiological considerations in DS patients might lead to challenges in adequate pain management and sedation after surgery. The aim of this systematic review and meta-analysis is to evaluate the variations of the requirement needed for pain management and sedation in patients with DS who have undergone surgery compared to patients without DS. Methods A systematic review and meta-analysis of studies were conducted, focusing on critically ill patients with DS who were admitted to Intensive care units (ICUs) post-surgery and received opioids and/or benzodiazepines. Searches were conducted in four databases from their inception to November 18, 2023 (Pubmed, Scopus, Cochrane Library, and Web of Science). The primary outcome measured was the dosage of Oral Morphine Equivalent (OME) administered in the days following surgery. Fixed-effect models were used, an approach advisable when only a limited number of studies are available. Results Out of the 992 studies initially screened, the systematic review included ten studies, encompassing 730 patients, while the meta-analysis consisted of seven studies, encompassing 533 patients. Of the seven studies included in the analysis, 298 patients were identified to have DS, and 235 patients served as controls. Patients with DS showed a slight increase in OME needs on the first day, but this increase was not statistically significant (mean difference [MD] = 0.09; 95% Confidence Interval [CI]: [-0.02, 0.20]; P = 0.11). There was also no significant difference in the requirement for Midazolam on the first day among DS patients (MD = 0.01; CI [-0.16, 0.19]; P = 0.88). In addition, the duration of mechanical ventilation was not statistically significant in patients with DS compared with the control group (MD = -1.46 hours; 95% CI [-9.74, 6.82]; P = 0.73). Conclusion Patients with Down syndrome did not require more sedation or analgesia in the first three days after surgery than patients without Down syndrome. Additionally, the two groups showed no significant difference in the duration of mechanical ventilation.

Background: Down syndrome (DS), or Trisomy 21, is defined by the existence of an additional chromosome 21. Various physiological considerations in DS patients might lead to challenges in adequate pain management and sedation after surgery. The aim of this systematic review and meta-analysis is to evaluate the variations of the requirement needed for pain management and sedation in patients with DS who have undergone surgery compared to patients without DS. Methods: A systematic review and meta-analysis of studies were conducted, focusing on critically ill patients with DS who were admitted to Intensive care units (ICUs) post-surgery and received opioids and/or benzodiazepines. Searches were conducted in four databases from their inception to November 18, 2023 (Pubmed, Scopus, Cochrane Library, and Web of Science). The primary outcome measured was the dosage of Oral Morphine Equivalent (OME) administered in the days following surgery. Fixed-effect models were used, an approach advisable when only a limited number of studies are available. Results: Out of the 992 studies initially screened, the systematic review included ten studies, encompassing 730 patients, while the meta-analysis consisted of seven studies, encompassing 533 patients. Of the seven studies included in the analysis, 298 patients were identified to have DS, and 235 patients served as controls. Patients with DS showed a slight increase in OME needs on the first day, but this increase was not statistically significant (mean difference [MD] = 0.09; 95% Confidence Interval [CI]: [-0.02, 0.20]; P = 0.11). There was also no significant difference in the requirement for Midazolam on the first day among DS patients (MD = 0.01; CI [-0.16, 0.19]; P = 0.88). In addition, the duration of mechanical ventilation was not statistically significant in patients with DS compared with the control group (MD = -1.46 hours; 95% CI [-9.74, 6.82]; P = 0.73). Conclusion: Patients with Down syndrome did not require more sedation or analgesia in the first three days after surgery than patients without Down syndrome. Additionally, the two groups showed no significant difference in the duration of mechanical ventilation. [ABSTRACT FROM AUTHOR]

Introduction: Down syndrome (DS) negatively impacts the well-being of affected individuals. This study aimed to summarise the evidence on quality of life (QOL) of children and young adults with DS using quantitative measures from caregivers’ perspective and identify factors that affected their QOL. Method: Database search was conducted on PubMed, Embase, Web of Science and CINAHL on 24 April 2024. Meta-analysis using random effects model was conducted where feasible. All studies underwent qualitative synthesis. The study protocol was registered with PROSPERO (CRD42023413532). Results: Seventeen studies involving 3038 children with DS using various QOL measures were included: Pediatric Quality of Life Inventory (PedsQL) (8 studies), KIDSCREEN (4 studies), KidsLife (2 studies), The Netherlands Organization for Applied Scientific Research Academic Medical Center Children’s QOL (2 studies) and Personal Outcome Scale (1 study). Meta-analysis on PedsQL studies compared scores between children with DS and typically developing (TD) children. Total scale score was lower in children with DS (mean 70.28, 95% confidence interval [CI] 64.31–76.24) compared to TD children (mean 88.17, 95% CI 80.50–95.83). All subdomains of PedsQL were also lower in children with DS. Within the domain of psychosocial health, children with DS had statistically significant lower social functioning (standardised mean difference -1.40, 95% CI -2.27 to -0.53) and school functioning (standardised mean difference -1.09, 95% CI -1.55 to -0.62) scores, but similar emotional functioning scores. Qualitative synthesis revealed poorer subdomain QOL compared to TD children, especially in social functioning and cognitive functioning. QOL worsened during adolescent years. Family variables (parental education and occupation) did not affect parental perception of children’s QOL. Children with DS who had higher intelligent quotient had better QOL. Conclusion: Children with DS have lower caregiver-reported QOL than TD children, especially in social functioning and school functioning subdomains. [ABSTRACT FROM AUTHOR]

Introduction: The aims of this systematic review and meta-analysis are to synthesise quality of life (QOL) of family caregivers of children and young adults with Down syndrome (DS) and determine factors affecting their QOL. Method: This review was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Key search terms were “quality of life”, “down syndrome” and “trisomy 21”. Meta-analysis using random effect model was conducted where feasible. All studies underwent qualitative synthesis. The study protocol was registered with PROSPERO (CRD42023413532). Results: Eighteen studies with 1956 caregivers were included. Of the 10 studies utilising the World Health Organization Quality of Life Instrument-Brief Version, 5 were included in the meta-analysis. Psychosocial domain had the highest score with mean (95% confidence interval [CI]) of 63.18 (39.10–87.25). Scores were poorer in physical, environmental and social domains: 59.36 (28.24–90.48), 59.82 (19.57–100.07) and 59.83 (44.24–75.41), respectively. Studies were heterogenous with I² values ranging from 99–100% (P<0.01). The remaining 8 studies used 6 other instruments. Qualitative synthesis revealed that caregivers’ QOL was adversely affected by child-related factors, such as level of functional independence, developmental delay, presence of multiple comorbidities, impaired activities of daily living and poor sleep quality. Environmental factors that adversely affected caregivers’ QOL included number of children, housing and support from the family. Personal factors that affected caregivers’ QOL included age, being a single mother, low education and low income. Conclusions: QOL of caregivers of children with DS was lower than population reference data. Understanding the factors that influence family caregivers’ QOL is an essential step towards improving the QOL of caregivers and their children with DS. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusion\nLAY SUMMARYPotential clinical interventions to mitigate or eliminate symptoms of Down syndrome (DS) continue to be an active area of pre-clinical and clinical research. However, views of members of the DS community have yet to be fully explored.We conducted a survey with parents/caregivers of people with DS (n = 532) to explore interest in potential therapeutic approaches during fetal development or childhood that may improve neurocognition and modulate the DS phenotype. We qualitatively analyzed open-ended responses.Some respondents rejected the development of therapies for DS categorically as being fundamentally ableist and promoting the erasure of diverse individuals. Many reflected tensions between the desire to improve quality of life and an aversion to erasure of a child’s personality.Findings suggest that views on identity, personality, and disability may influence the acceptance of new interventions, especially if they are thought to mitigate positive attributes of the phenotype or negatively influence social acceptance of people with DS.Prenatal and pediatric approaches to reduce the signs of Down syndrome are being investigated.Parents of children with Down syndrome expressed conflicted feelings about the idea of removing signs of Down syndrome from their child.Many parents expressed that Down syndrome was a valued part of their child and should not be taken away.Findings suggest that greater communication between the Down syndrome community and the research community is necessary to ensure that research aligns with their values and priorities of the patient community.Prenatal and pediatric approaches to reduce the signs of Down syndrome are being investigated.Parents of children with Down syndrome expressed conflicted feelings about the idea of removing signs of Down syndrome from their child.Many parents expressed that Down syndrome was a valued part of their child and should not be taken away.Findings suggest that greater communication between the Down syndrome community and the research community is necessary to ensure that research aligns with their values and priorities of the patient community. [ABSTRACT FROM AUTHOR]

Objectives: Objective of this study was to describe orthodontic findings in adults with Down’s syndrome, a matter insufficiently regarded in literature. Materials and methods: A group of 104 adults (33.8 ± 15 years) with trisomy 21 had an orthodontic check-up in their accustomed environment. Anamnestic and dental findings completed the examination and descriptive analysis was performed using SPSS23. Relative frequencies with 95% confidence intervals were compared to the average population (SHIP-study, 2003; DMS IV, 2006). Results: Among the participants 46.2% (36.3–56.2%) (SHIP 36.7%) had already undergone orthodontic treatment. In 87.5% (79.6–93%) of the patients, less than 25.6 properly functioning permanent teeth (DMS IV’s mean) were found. Gingival bleeding and recessions, as well as periodontal disease, were increasingly found in older affected persons. Patients with Down’s syndrome showed less crowding, e.g., maxillary incisors 28% (19.3–39%) versus 41.9% (SHIP). Frontal open bite (35.2% (25.3–46.1%) versus 3.6% (SHIP)) and frontal crossbite (40.9% (30.5–51.9%) versus 4.2% (SHIP)) were more often observed. No considerable differences in frequencies of orthodontic findings were detected in the comparison of the subgroups “18–28 years” versus “>28 years”, “with” versus “without orthodontic treatment”, “male” versus “female”, “with” versus “without periodontal problems”, or “with” versus “without orofacial disturbances”. Conclusions: Within the bounds of this study, we gathered orthodontic findings in adults with trisomy 21 for the first time. In comparison to the average population, the subject group showed a greater number of complex orthodontic findings. Clinical relevance: These persisting dental and orofacial problems must be considered when treating patients with Down’s syndrome. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Infantile epileptic spasms syndrome (IESS) with Down syndrome has good treatment response and good seizure outcomes with high-dose adrenocorticotrophic hormone (ACTH) therapy. We investigated the early treatment response of epileptic spasms (ES), long-term seizure outcome, and efficacy of very-low-dose ACTH therapy for IESS with Down syndrome. We retrospectively investigated patients with Down syndrome and IESS between April 1983 and January 2023. We defined response to treatment as clinical remission and electrographic resolution of hypsarrhythmia after treatment for more than one month and early treatment as any treatment for ES within three months of initiation of treatment. Long-term seizure outcomes were determined by the presence of any type of seizure within one year of the last visit. We investigated the dosage and efficacy of very-low-dose ACTH therapy. Thirty patients were enrolled with a median follow-up period of 7.7 years (range: 1.3 to 19.1). The response and relapse rates in the early treatment were 83.3% and 16.0%, respectively. The seizure-free rate of long-term seizure outcomes was 80.0%. Long-term seizure outcomes correlated with early treatment response to ES. The response rate of very-low-dose ACTH therapy was 59.3%. The efficacy of ACTH therapy tended to be dose-dependent (P = 0.055). Early treatment response to ES may be useful in predicting long-term seizure outcomes of IESS with Down syndrome. Very-low-dose ACTH therapy was the most effective treatment for ES and could exhibit dose-dependent efficacy. Depending on the IESS etiology, the ACTH dose could be reduced to minimize its side effects. [ABSTRACT FROM AUTHOR]

The one‐carbon metabolism pathway is involved in critical human cellular functions such as cell proliferation, mitochondrial respiration, and epigenetic regulation. In the homocysteine‐methionine cycle S‐adenosyl‐methionine (SAM) and S‐adenosyl‐homocysteine (SAH) are synthetized, and their levels are finely regulated to ensure proper functioning of key enzymes which control cellular growth and differentiation. Here we review the main biological mechanisms involving SAM and SAH and the known related human diseases. It was recently demonstrated that SAM and SAH levels are altered in plasma of subjects with trisomy 21 (T21) but how this metabolic dysregulation influences the clinical manifestation of T21 phenotype has not been previously described. This review aims at providing an overview of the biological mechanisms which are altered in response to changes in the levels of SAM and SAH observed in DS. [ABSTRACT FROM AUTHOR]

Williams syndrome (WS) and Down syndrome (DS) are two neurodevelopmental disorders with distinct genetic origins characterized by mild to moderate intellectual disability. Individuals with WS or DS exhibit impaired hippocampus‐dependent place learning and enhanced striatum‐dependent spatial response learning. Here, we used the Weather Prediction Task (WPT), which can be solved using hippocampus‐ or striatum‐dependent learning strategies, to determine whether individuals with WS or DS exhibit similar profiles outside the spatial domain. Only 10% of individuals with WS or DS solved the WPT. We further assessed whether a concurrent memory task could promote reliance on procedural learning to solve the WPT in individuals with WS but found that the concurrent task did not improve performance. To understand how the probabilistic cue–outcome associations influences WPT performance, and whether individuals with WS or DS can ignore distractors, we assessed performance using a visual learning task with differing reward contingencies, and a modified WPT with unpredictive cues. Both probabilistic feedback and distractors negatively impacted the performance of individuals with WS or DS. These findings are consistent with deficits in hippocampus‐dependent learning and executive functions, and reveal the importance of congruent feedback and the minimization of distractors to optimize learning in these two populations. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsTo assess the management of patients with congenital nasolacrimal duct obstruction (CNLDO) in a paediatric population and review the long-term outcomes over a 5-year interval, with particular emphasis on the difference between patients with trisomy 21 and those without trisomy 21.This single-centre, retrospective, cross-sectional, case review study included patients suffering from CNLDO at Alder Hey Children’s Hospital NHS foundation Trust. Patients were divided into two groups: Non-trisomy 21 and trisomy 21. Patients were followed-up for a 60-month interval. Patients aged <12 months at the time of surgery, patients with <60 months of follow-up data and patients with acquired nasolacrimal duct obstruction were excluded. The main outcome measures were discharge rates in patients undertaking primary intervention with syringe and probe (S&P), number of patients requiring further treatment with lacrimal intubation or dacryocystorhinostomy (DCR) and overall symptom-free periods post-treatment.Ninety-three patients (142 eyes) were included. The mean number of surgical interventions was 1.53 ± 0.65. The mean interval between the 1st and 2nd intervention was 15.54 ± 16.33 months. There was a trend towards greater success rates non-trisomy 21 patients versus patients with trisomy 21 (p = 0.1352). The average symptom-free period after the final intervention was 44.31 ± 20.68 months, significantly longer in the non-trisomy 21 group compared to the trisomy 21 group (p = 0.0074).The overall success rate after primary S&P was 55.9%. Our results suggest that in trisomy 21 patients suffering from CNLDO, a one-stage intervention with primary monocanalicular intubation should be considered instead of sequential approach. [ABSTRACT FROM AUTHOR]

Trisomy 21 (T21) is a genetically determined human condition that occurs in one in every 800 births worldwide. Improvements in lifelong care have generated discussion about the mental health of people with T21. However, suicidal behavior in this population has still received little attention. This integrative review aimed to understand and synthesize scientific production on the topic of 'suicide in people with T21'. We conducted the review in the Virtual Health Library, PubMed, and PsycInfo databases using the descriptors 'Down syndrome', 'Down's syndrome', and 'trisomy 21' in combination with 'suicide', 'suicide attempted', and 'suicidal ideation'. We analyzed articles published until 10th October 2023. The selected articles were evaluated for their level of evidence and categorized thematically. Eight articles from three countries met the eligibility criteria: three case reports, three narrative literature reviews, one observational cross-sectional study, and one cohort study. The articles were organized and discussed in four categories: (1) scientific literature impressions about suicide in individuals with T21; (2) T21 life course issues and forms of expression of suicidal behavior; (3) suicide frequency in individuals with T21; and (4) possible implications for caring for individuals with T21 who exhibit suicidal behavior. The results revealed a lack of literature on the subject, which indicates the need for additional research. Based on the evidence available, suicidal behavior among people with T21, while a possible phenomenon, seems uncommon. Health professionals should investigate T21 individuals' mental health, searching for depression and self-injury symptoms. [ABSTRACT FROM AUTHOR]

Objectives: The performance of non‐invasive prenatal screening using cell‐free DNA testing of maternal blood in twin pregnancy is underevaluated, while serum marker‐based strategies yield poor results. This study aimed to assess the performance of non‐invasive prenatal screening for trisomy 21 in twin pregnancy as a first‐tier test. Secondary objectives were to assess its failure rate and factors associated with failure. Methods: This retrospective cohort study included twin pregnancies in which non‐invasive prenatal screening using cell‐free DNA was performed as the primary screening strategy between May 2017 and October 2019. We used the NIPT VeriSeq® test for in‐vitro diagnosis and set a fetal fraction cut‐off of 4% for monochorionic pregnancies and 8% for dichorionic ones. Clinical data and pregnancy outcome were collected from physicians or midwives via a questionnaire or were retrieved directly on‐site. We calculated the performance of non‐invasive cell‐free DNA screening for trisomy 21, analyzed its failure rate and assessed potentially associated factors. Results: Among 1885 twin pregnancies with follow‐up, there were six (0.32%) confirmed cases of trisomy 21. The sensitivity of non‐invasive prenatal screening for trisomy 21 was 100% (95% CI, 54.1–100%) and the false‐positive rate was 0.23% (95% CI, 0.06–0.59%). The primary failure rate was 4.6%, with 4.0% being due to insufficient fetal fraction. A successful result was obtained for 65.4% of women who underwent a new blood draw, reducing the overall failure rate to 2.8%. Maternal body mass index, gestational age at screening as well as chorionicity were significantly associated with the risk of failure. Conclusion: This study provides further evidence of the high performance, at an extremely low false‐positive rate, of non‐invasive prenatal screening in twins as part of a primary screening strategy for trisomy 21. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Newborn screening (NBS) for severe combined immunodeficiency (SCID) has been widely implemented to enable early detection and intervention. Trisomy 21, commonly known as Down syndrome (DS), poses unique challenges in NBS due to its frequent association with T and/or B cell lymphopenia. The pilot NBS screening program recently conducted in Russia was aimed to identify both severe T and B cell deficiencies by measuring TREC and KREC. This study aims to evaluate the incidence of DS in newborns who participated in the pilot program, assess their TREC and KREC values, and determine the proportion of DS newborns potentially identifiable through T/B lymphopenia NBS. We conducted a retrospective analysis of the data obtained during the pilot NBS program, involving 202,908 newborns from eight regions of Russia. The study identified 157 patients with trisomy 21 among the screened cohort, resulting in a DS birth prevalence of 1:1,284. Median TREC and KREC values did not significantly differ between full-term and pre-term subgroups of DS patients. TREC values in DS newborns were decreased and comparable to those of the extremely preterm newborns. DS newborns also demonstrated significant differences in KREC values as compared to the general cohort regardless of gestational age. Our data suggests abnormalities of T- and B-cell lineages development and requires further investigation. This article highlights the need for increased awareness of the intrinsic immunological defects associated with DS. The findings underscore the importance of continued follow-up and comprehensive support by healthcare teams for individuals with DS.

Transient Abnormal Myelopoiesis (TAM) is a transient haematological condition observed in children with Down syndrome during their neonatal period. Spontaneous resolution without any specific treatment is the rule, and the condition is known to occur exclusively in association with trisomy 21. Around 10% of Down syndrome babies are known to be affected by TAM, and 20-30% of these babies are known to develop acute myeloid leukaemia, of the megakaryoblastic type, in their later lives. Multisystem involvement is known in this condition. The present case of TAM is a two-day-old newborn female baby, born out of full-term gestation, presented with respiratory distress along with congenital pneumonia, hepatosplenomegaly, and mild ascites. The baby also had significant pulmonary hypertension, an Atrial Septal Defect (ASD), and non restrictive Patent Ductus Arteriosus (PDA). A significant increase in the total leukocyte count was seen, accompanied by thrombocytosis and 72% blastoid cells. Then, using karyotyping, Trisomy 21 was verified. 35% of the blasts had megakaryoblastic differentiation, according to flow cytometry. Hence, before diagnosing congenital leukaemia based on finding excess blasts in the peripheral smear of a newborn, karyotyping has to be done to look for possible trisomy 21. It can be an incidental finding, as in the present case, without prior clinical suspicion of Down syndrome.

Scant research has explored the healthcare experiences of people with Down syndrome (DS) in the United States who are Black, African American, of African descent, or of mixed race. The purpose of this study was to identify and describe the barriers and facilitators that such patients and their caregivers face when accessing healthcare. We gathered data in three ways: focus groups with caregivers, a national survey completed by caregivers, and in-depth interviews with primary care providers. Many caregivers and primary care physicians felt that patients with DS who are Black, African American, of African descent, or of mixed race receive a lower quality of medical care than their white counterparts with DS. Caregivers mentioned feeling tired of being reminded by the medical community about their race and wanting acknowledgment that raising a child with DS can be hard at times. Many felt that the medical communitys conscious and unconscious racial biases do negatively impact the care of their loved ones with DS. Caregivers desired more race concordant medical providers or, when not possible, medical providers who are willing to learn more about DS and build trusted, longitudinal relationships. Primary care providers discussed the need for funded resources and support services to effectively care for their patients with DS.

Pulmonary disease, lower respiratory tract infection, and pneumonia are the largest causes of morbidity and mortality in individuals with Down syndrome (DS), but whether pulmonary diagnoses in children with DS are common and occur independently of cardiac disease and pulmonary hypertension (PH) is unknown. Cardiopulmonary phenotypes were examined in a cohort of 1248 children with DS. Aptamer-based proteomic analysis of blood was performed in a subset (n = 120) of these children. By the age of 10 years, half of the patients in this cohort (n = 634, 50.8%) had co-occurring pulmonary diagnoses. That proteins and related pathways were distinct between children with pulmonary diagnoses and those with cardiac disease and/or PH may indicate that pulmonary diagnoses appear to occur independently of cardiac disease and PH. Heparin sulfate-glycosaminoglycandegradation, nicotinate metabolism, and elastic fiber formation were ranked highest in the group with pulmonary diagnoses. [ABSTRACT FROM AUTHOR]

Aim: Five to thirty percent of neonates with trisomy 21 develop transient abnormal myelopoiesis (TAM) with a high mortality rate. The aim of the study was to identify contributing factors that determine mortality and need for chemotherapy in this patient group. Methods: Six‐year, single‐centre, retrospective study of neonatal TAM cases requiring admission to intensive care. Data were collected from electronic patient records, laboratory and genetic results. The odds ratio was calculated to assess the likelihood of neonates with certain clinical characteristics having short‐term mortality and needing chemotherapy. Results: Twenty‐one neonates were studied with a mortality rate of 28%. Neonates requiring inotropic support (OR 19, 95% CI: 0.9–399, p = 0.05) and inhaled nitric oxide (iNO) (OR 13, 95% CI: 1.4–124.3, p = 0.03) were less likely to survive to discharge. Neonates needing mechanical ventilation (OR 14, 95% CI: 1.1–185.5, p = 0.04), or a white cell count >50 × 109/L (OR 27, 95% CI: 1.2–605.7, p = 0.04) were more likely to receive chemotherapy. Conclusion: A high mortality rate was identified in TAM neonates with symptomatic pulmonary hypertension (PH) needing active treatment strategies, such as inotropes and iNO. The presence of PH should be considered in the clinical management, prognosis and parental counselling. [ABSTRACT FROM AUTHOR]

Aim: In this study, we compared the ratio of second trimester fetal biometric measurements to nasal bone length (NBL) in fetuses with normal karyotype and trisomy 21 to determine their diagnostic prognostic value. Materials and Methods: The study included 148 pregnant women who obtained second‐trimester ultrasonographic fetal anatomy and had amniocentesis (AS) for fetal karyotyping. The fetal karyotype results divided the groups into normal and trisomy 21 fetuses. Age, obstetric history, first and/or second trimester screening test risk ratios, fetal biometric measurements, and NBL mm, median (MoM) multiples, and percentile values were recorded and compared between groups. Results: BPD/NBL ratios above 9.26 predict trisomy 21 in fetuses with 77.6% sensitivity and 86.1% specificity (p = 0.001). HC/NBL ratios above 34.50 predict trisomy 21 in fetuses with 77.8% sensitivity and 88.8% specificity (p = 0.001). FL/NBL ratios above 6.02 predict trisomy 21 in fetuses with 69.6% sensitivity and 72.2% specificity (p = 0.001). HL/NB ratios above 6.56 predict trisomy 21 in fetuses with 95.5% sensitivity and 47.2% specificity (p = 0.001). The NBL MoM value demonstrated a high diagnostic accuracy for normal‐karyotype fetuses (p = 0.021). Conclusion: We found that BPD/NBL, HC/NBL, FL/NBL, and HL/NBL ratios differed between fetuses with a normal karyotype and those with trisomy 21, specifically the HC/NBL ratio, which predicted trisomy 21 with good diagnostic accuracy. In identifying normal‐karyotype fetuses, the NBL MoM was highly accurate. [ABSTRACT FROM AUTHOR]

Objectives: Intracapsular tonsillectomy and adenoidectomy (iTA) has become a popular alternative to extracapsular tonsillectomy and adenoidectomy (TT) for the treatment of pediatric obstructive sleep apnea (OSA) due to improved recovery and fewer complications. The objective of this study was to compare surgical recovery and impact on OSA of iTA versus TT in patients with Trisomy 21 (T21). Methods: This is a case series with chart review of all T21 patients who underwent iTA or TT at our institution between July 1, 2015 and August 15, 2022. Data collected included demographics, comorbidities, preoperative sleep studies, intraoperative data, complications and recovery, postoperative sleep studies, and follow‐up data. Results: There were 62 (21.7%) patients who underwent iTA and 224 (78.3%) patients who underwent TT. The iTA group had significantly lower pain scores (p < 0.001), decreased use of narcotics (p < 0.001), shorter length of stay (p = 0.003), and faster return to oral intake (p = 0.01) during their postoperative hospital admission, and fewer 30‐day complications (p = 0.009) compared to the TA group. Both groups showed significant improvements in their sleep studies. For 41 (66.1%) of iTA patients who had follow‐up, median follow‐up was 1.8 years and for 169 (75.4%) TT patients, median follow‐up was 2.6 years. At follow‐up, 21 of 41 (51.2%) iTA patients and 83 of 169 (49.1%) TT patients exhibited OSA symptoms (p = 0.084) and tonsillar regrowth was not significantly different between the two groups (p = 0.12). Conclusion: Patients with T21 experience less pain and fewer postoperative respiratory complications from iTA than from TT. The short‐term impact of iTA versus TT on OSA, as measured by poysomnography, does not differ between the two techniques. Level of Evidence: 3 Laryngoscope, 134:2430–2437, 2024 [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

This perspective review aims to explore the potential neurobiological mechanisms involved in the application of transcranial Direct Current Stimulation (tDCS) for Down syndrome (DS), the leading cause of genetically-based intellectual disability. The neural mechanisms underlying tDCS interventions in genetic disorders, typically characterized by cognitive deficits, are grounded in the concept of brain plasticity. We initially present the neurobiological and functional effects elicited by tDCS applications in enhancing neuroplasticity and in regulating the excitatory/inhibitory balance, both associated with cognitive improvement in the general population. The review begins with evidence on tDCS applications in five neurogenetic disorders, including Rett, Prader-Willi, Phelan-McDermid, and Neurofibromatosis 1 syndromes, as well as DS. Available evidence supports tDCS as a potential intervention tool and underscores the importance of advancing neurobiological research into the mechanisms of tDCS action in these conditions. We then discuss the potential of tDCS as a promising non-invasive strategy to mitigate deficits in plasticity and promote fine-tuning of the excitatory/inhibitory balance in DS, exploring implications for cognitive treatment perspectives in this population. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the health literacy level of the parents of children diagnosed with Down syndrome (DS) within one institution in Turkey. Design/methodology/approach: A cross-sectional survey measuring demographics, information of the child and the parent and health literacy was administered to participants. The health literacy levels in the study were measured with the European Health Literacy Scale (EHLS), which consists of 47 questions. Findings: Of the 65 participants who completed the questionnaire, 56.9% were mothers, 68.1% were diagnosed in the neonatal outpatient clinic examination after birth, and 58.5% stayed in the neonatal intensive care unit after birth. The mean score of the IHLS scale was 25.06 ± 6.59. Of the parents, 63.1% were found to be inadequate, 18.5% problematic-limited, and 18.5% adequate health literate. Any parent with excellent health literacy level was identified. High education level (p < 0.001), high income level (p < 0.001), living in the city center (p < 0.05), planned pregnancy (p < 0.05) and being a health worker (p < 0.001) were found to be statistically significant with a high EHSL score. Research limitations/implications: The presence of Down syndrome (DS) in a child also necessitates ongoing monitoring for a range of conditions, including eye diseases and heart disease. Some surgical procedures, such as heart or gastrointestinal surgeries, may also be required. Additionally, the child may require the administration of various medications. Finally, due to the potential lifelong need for assistance, the child may require the support of an adult throughout their lifetime. This is because of the child's inability to live independently due to their mental state. Therefore, parent education is the most important issue in the follow-up of the disease. Practical implications: To the best of the authors' knowledge, this is the first study to determine that parents of children diagnosed with DS have very limited knowledge of the disease and health literacy. Explanation of current diseases, treatments and training of parents should also be included in genetic counseling. Social implications: DS is a chromosomal disease that requires multidisciplinary care. Parents have to know the course of the disease and its complications. Originality/value: The findings of this study indicate that parents of children with Down syndrome exhibit a profound lack of knowledge regarding the nature of their child's condition and the available healthcare options. It is therefore imperative that genetic counseling incorporates an explanation of the diagnosed diseases, treatments, and educational resources for parents. [ABSTRACT FROM AUTHOR]

Background: Down syndrome (DS) is distinguished by cognitive disability, a concave profile, and systemic complications. Oral diseases have been reported to be common in DS patients. Objective: To investigate the association between DS and periodontal diseases. Methods: Two independent reviewers searched six bibliographic databases up to January 2023 and used additional search methods to identify published studies on gingivitis or periodontitis in people with and without DS. Meta‐analysis, risk of bias, sensibility analysis, publication bias, and evidence grading were all carried out. Results: Twenty‐six studies were included for analysis. There was a tendency for increased plaque accumulation, periodontal probing, periodontal attachment level, bleeding on probing and indices in DS individuals. Meta‐analysis of 11 studies showed a significant association between DS and periodontitis (OR 3.93; 95% CI 1.81–8.53). Probing depth was significantly high in individuals with DS as compared to controls (mean difference 0.40 mm; 95% CI 0.09–0.70). Gingivitis was significantly associated (OR 1.93; 95% CI 1.09–3.41) with DS in four studies. The evidence was classified as 'moderate certainty'. Conclusion: Medium/low‐quality studies demonstrate that Down syndrome is strongly associated with periodontitis and moderately associated with gingivitis. [ABSTRACT FROM AUTHOR]

Backgroundobjectives: To compare the structural anatomy of the anterior segment in pediatric Trisomy 21 (T21) subjects with and without cataracts to age-matched controls. Design: Prospective case-control study. Participants: 40 subjects (57 eyes) age 0–25 years old (9.1 ± 10.6 years). Methods: This prospective case-control study evaluated anterior segment measurements from ultrasound biomicroscopy (UBM) imaging on 342 images. Results: Among persons with T21 cataract, the iris was significantly thinner than T21 individuals without cataract (0.28 vs 0.32 mm, p = 0.0181). T21/cataract subjects also had significantly thinner lenses than subjects without cataract, regardless of whether they have T21 or are controls (3.1 mm vs 3.5 mm, p = 0.0074).Thinner lens (

Background: Non-invasive prenatal tests (NIPT) are used to screen for trisomy 21, 18, and 13. This study investigated NIPT performance and the clinical significance of its results. Methods: Pregnant women (n = 282,911) participating in a free NIPT (April 2018–December 2021) were screened for common trisomies, and the results were retrospectively analyzed. NIPT performance was evaluated by its positive predictive value (PPV), sensitivity, and specificity. Results were analyzed using number, percentage, and chi-squared/t-test analyses. Results: After NIPT screening, patients with common trisomies (n = 746) included 457 with T21, 160 with T18, and 129 with T13. Seven false negative cases were identified. High PPV (86.81 %, 56.81 %, 18.18 %), sensitivity (99.25 %, 98.33 %, 100.00 %), and specificity (99.98 %, 99.98 %, 99.97 %) values were detected for trisomy 21, 18, and 13, respectively. The PPVs of common trisomies were significantly different between pregnant women older than 35 (85.53 %, 136/159) and those aged 35 or younger (58.90 %, 311/528) (χ2 = 125.02, P = 2.20e-16). As the NIPT uptake increased from 2018 to 2021, live-born birth defect incidence decreased. Conclusion: NIPT performed well in screening for T21, T18, and T13. Our discoveries offer an important and useful guideline in laboratory and clinical genetic counseling.

Abstract 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

Transient Abnormal Myelopoiesis (TAM) is a transient haematological condition observed in children with Down syndrome during their neonatal period. Spontaneous resolution without any specific treatment is the rule, and the condition is known to occur exclusively in association with trisomy 21. Around 10% of Down syndrome babies are known to be affected by TAM, and 20-30% of these babies are known to develop acute myeloid leukaemia, of the megakaryoblastic type, in their later lives. Multisystem involvement is known in this condition. The present case of TAM is a two-day-old newborn female baby, born out of full-term gestation, presented with respiratory distress along with congenital pneumonia, hepatosplenomegaly, and mild ascites. The baby also had significant pulmonary hypertension, an Atrial Septal Defect (ASD), and non restrictive Patent Ductus Arteriosus (PDA). A significant increase in the total leukocyte count was seen, accompanied by thrombocytosis and 72% blastoid cells. Then, using karyotyping, Trisomy 21 was verified. 35% of the blasts had megakaryoblastic differentiation, according to flow cytometry. Hence, before diagnosing congenital leukaemia based on finding excess blasts in the peripheral smear of a newborn, karyotyping has to be done to look for possible trisomy 21. It can be an incidental finding, as in the present case, without prior clinical suspicion of Down syndrome. [ABSTRACT FROM AUTHOR]

Background: To enhance the efficacy of maternal serum screening (MSS), we conducted an analysis to examine the correlation between certain factors identified during second-trimester screening (STS) and fetal chromosomal abnormalities, excluding the common trisomies (trisomies 13, 18, and 21). Additionally, specific risk factor ranges were established for each category. Methods: A retrospective 1:3 matched case-control study was conducted. Case data were obtained from 311 STS samples of fetal chromosomal abnormalities other than common trisomies, with testing performed in the Prenatal Diagnosis Center of the Maternal and Child Health Care Hospital of Sichuan Province in China between 6 January 2013 and 12 April 2023. A total of 933 controls were matched accordingly. Univariate and multivariable conditional logistic regression analyses were implemented and sensitivity analysis was performed. Results: Multivariable logistic analyses revealed that the independent risk factors for fetal chromosomal abnormalities other than common trisomies were ultrasonographic structural abnormalities (odds ratio (OR) = 3.038; 95% confidence interval (CI), 1.774–5.202; p < 0.001); free β-human chorionic gonadotropin (free β-hCG) as multiples of the median (MoMs) of ≤0.34 (OR = 3.006; 95% CI, 1.803–5.013; p < 0.001), 2.82–3.53 (OR = 1.884; 95% CI, 1.321–2.688; p < 0.001), 3.54–4.67 (OR = 1.949; 95% CI, 1.300–2.923, p = 0.001), and ≥4.68 (OR = 1.730; 95% CI, 1.045–2.866; p = 0.033); and a trisomy 21 (T21) risk of 1/271–1/1000 (OR = 2.434; 95% CI, 1.706–3.472; p < 0.001), 1/101–1/270 (OR = 3.330; 95% CI, 2.300–4.821; p < 0.001), and ≥1/100 (OR = 3.441; 95% CI, 2.178–5.438; p < 0.001). Conclusions: Ultrasonographic structural abnormalities, free β-hCG MoMs, and T21 risk were identified as independent risk factors for fetal chromosomal abnormalities (with the exception of common trisomies) in STS. Our findings thus provide data to support clinical decision-making.

IntroductionPeople with Down syndrome (DS) are predisposed to Alzheimer's disease (AD). The amyloid hypothesis informs studies of AD. In AD-DS, but not sporadic AD, increased APP copy number is necessary, defining the APP gene dose hypothesis. Which amyloid precursor protein (APP) products contribute needs to be determined.MethodsBrain levels of full-length protein (fl-hAPP), C-terminal fragments (hCTFs), and amyloid beta (Aβ) peptides were measured in DS, AD-DS, non-demented controls (ND), and sporadic AD cases. The APP gene-dose hypothesis was evaluated in the Dp16 model.ResultsDS and AD-DS differed from ND and AD for all APP products. In AD-DS, Aβ42 and Aβ40 levels exceeded AD. APP products were increased in the Dp16 model; increased APP gene dose was necessary for loss of vulnerable neurons, tau pathology, and activation of astrocytes and microglia.DiscussionIncreases in APP products other than Aβ distinguished AD-DS from AD. Deciphering AD-DS pathogenesis necessitates deciphering which APP products contribute and how.