Down Syndrome Research Articles

Genome-wide association studies of Down syndrome associated congenital heart defects.

Congenital heart defects (CHDs) are the most common structural birth defect and are present in 40-50% of children born with Down syndrome (DS). To characterize the genetic architecture of DS-associated CHD, we sequenced genomes of a multiethnic group of children with DS and a CHD (n=886: atrioventricular septal defects (AVSD), n=438; atrial septal defects (ASD), n=122; ventricular septal defects (VSD), n=170; other types of CHD, n=156) and DS with a structurally normal heart (DS+NH, n=572). We performed four GWAS for common variants (MAF>0.05) comparing DS with CHD, stratified by CHD-subtype, to DS+NH controls. Although no SNP achieved genome-wide significance, multiple loci in each analysis achieved suggestive significance (p<2×10-6). Of these, the 1p35.1 locus (near RBBP4) was specifically associated with ASD risk and the 5q35.2 locus (near MSX2) was associated with any type of CHD. Each of the suggestive loci contained one or more plausible candidate genes expressed in the developing heart. While no SNP replicated (p<2×10-6) in an independent cohort of DS+CHD (DS+CHD: n=229; DS+NH: n=197), most SNPs that were suggestive in our GWASs remained suggestive when meta-analyzed with the GWASs from the replication cohort. These results build on previous work to identify genetic modifiers of DS-associated CHD.

Frailty in Persons with Down Syndrome: Results from the REVIVIS Study

ObjectivesTo determine frailty prevalence and identify possible nonclinical factors associated with this condition in community-dwelling individuals with Down syndrome (DS). DesignCross-sectional analysis of the registry study REVIVIS, a single-center, prospective study on the geriatric management of persons with DS. Setting and ParticipantsIndividuals with DS (n = 139) referred to a geriatric clinic. MethodsFrailty was assessed through a 38-item Frailty Index (FI). A multivariable linear regression model was performed to assess the relationship between frailty and different variables of interest: age, number of prescribed drugs, and employment status (unemployed vs employed). ResultsAmong 139 subjects (54.5% male), mean (SD) aged 42.9 (6.9) years, the median (interquartile range) FI was 0.24 (0.16-0.30) with 60 participants (43.2%) classified as frail. The number of prescribed medications was associated with higher FI levels (P < .001), whereas being employed was associated with lower FI levels (P < .001) compared with being unemployed. No association was found between chronological age and FI. Conclusions and ImplicationsOur findings suggest that chronological age is insufficient to encompass the complexity of a subject with DS, underscoring the importance of a standardized evaluation of the FI among this population. Access to geriatric care might become an important opportunity for people with DS, a population characterized by high vulnerability (or frailty).

Three-dimensional assessment of the nasopharyngeal airway in Down syndrome during the mixed dentition period: a case-control study.

In this retrospective case-control study, we aimed to evaluate the nasopharyngeal airway volume of children with Down syndrome (DS) and compare the results with those of control participants well matched for sex and age. Fifteen children with DS (mean age = 9.43 ± 0.38 years; 8 boys, 7 girls) and 15 control participants (mean age = 9.51 ± 0.40 years; 8 boys, 7 girls) were enrolled. The nasopharyngeal airway volume and the cross-sectional morphology were measured with cone-beam computed tomography taken for orthodontic treatment. All measurements were assessed by analysis of covariance (ANCOVA) using Bonferroni post hoc pairwise comparison tests. Covariates were body height and body weight, and the ANB angle and the mandibular plane angle. Significance was set at P < .0019. Nasal airway, superior airway, and total airway volumes of DS participants were significantly smaller than those of the control participants in ANCOVA results adjusted for ANB angle and mandibular plane angle (P = .000). In ANCOVA results adjusted for body height and body weight, no statistically significant differences in the volume measurements were found. The results indicate that the nasopharyngeal airway volume differs between children with and without DS and that the airway volume tends to be smaller in DS children than in children without DS.

Can we talk? A correspondence study to examine responsiveness of physical educators to requests for a phone call from parents of children with disabilities

ABSTRACT The Individuals with Disabilities Education Improvement Act (2004) mandates that parental input be considered when making educational decisions for children with disabilities, including in physical education. However, parents of children with disabilities often report suboptimal communication experiences with physical educators. The purpose of the current study was to examine if the initiation of a parent–physical educator relationship is influenced by whether students have a disability or not. An online message correspondence study methodology was used to detect potential disparities in the responsiveness of a sample of 320 physical educators to electronic message requests for a phone call to discuss physical education service from hypothetical parents of a child with a visual impairment (VI), autism spectrum disorder (ASD), Down syndrome (DS), or no disability. Parents of children with ASD had reduced odds of receiving a positive response as compared to parents of children without disabilities (15.8% vs 26.9% RR = .57). Similarly, parents of children with DS had reduced odds of receiving a positive response as compared to parents of children without disabilities (15.2% vs 26.9%, RR = .59). Strategies to promote parent–physical educator relationships are urgently needed, especially for parents of children with ASD and DS.

Scheimpflug Tomographic Indices for Classifying Normal, Down Syndrome and Clinical Keratoconus in Pediatric Patients.

The study aimed to evaluate the precision of different Pentacam indices in diagnosing keratoconus (KC) in pediatric patients with and without Down Syndrome (DS) and determine suitable cutoff values. This prospective multicenter cross-sectional study evaluated 216 eyes of 131 patients aged 6-18 years (mean age 12.5 ± 3.2 years) using Pentacam. Patients were categorized into four groups: KC, forme fruste keratoconus (FK), DS, and control, excluding DS patients with topographic KC. Receiver operating characteristic curves were generated to determine the optimal cutoff points and compare the accuracy in identifying KC and FK in patients with and without DS. In DS patients, corneal morphology resembled KC features. The most effective indices for distinguishing KC in DS patients were the average pachymetric progression index (AUC = 0.961), higher-order aberration of the anterior cornea (AUC = 0.953), anterior elevation (AUC = 0.946), posterior elevation (AUC = 0.947), index of vertical asymmetry (AUC = 0.943), and Belin/Ambrosio enhanced ectasia total derivation value (AUC = 0.941). None of the indices showed good accuracy for distinguishing FK in DS patients. The thresholds of these indices differed significantly from non-DS patients. The results highlighted the need for DS-specific cutoff values to avoid false-positive or false-negative diagnoses in this population.

Exploring the Impact of Swimming on Body Mass Index and Body Fat in Individuals with Down Syndrome: A Meta-Analysis

The aim of this study is to assess the effectiveness of swimming training in reducing body mass index (BMI) and body fat percentage among individuals with Down syndrome (DS), utilizing a meta-analysis approach. We conducted a systematic search for studies examining the clinical impact of swimming training on individuals with DS. Inclusion criteria encompassed studies involving DS patients who underwent swimming training for a minimum duration of 4 weeks. The primary focus was to compare changes in BMI and body fat percentage from baseline to post-training. Our analysis incorporated four studies comprising a total of 48 participants. The results demonstrated that swimming training lasting from 8 to 36 weeks did not significantly decrease BMI among DS patients, with a weighted mean difference (WMD) post-training of −0.428 (95% confidence interval (CI): −1.721–0.865) and an I2 of 0%. Subgroup analysis based on age or duration (≥33 weeks or 8 weeks) also showed no notable decrease in BMI. Conversely, the analysis of body fat percentage demonstrated a significant decrease, with a WMD of −2.946 (95% CI: −5.056–−0.837). Subgroup analysis indicated a consistent reduction in body fat percentage across all duration groups. Swimming training does not lead to a significant reduction in BMI among individuals with DS. This outcome may be attributed to concurrent muscle gain alongside decreased body fat, resulting in a notable decrease in body fat percentage.

The effect of age on congenital nasolacrimal duct obstruction probing and stent intubation outcomes in pediatric Down syndrome patients

PurposeTo examine the effect of age at time of congenital nasolacrimal duct obstruction (CNLDO) intervention on symptom resolution and reoperation rates in patients with Down syndrome (DS). MethodsThe medical records of patients with DS and CNLDO between 2012 and 2021 were reviewed retrospectively. Age at the time of first stent placement was utilized to categorize patients into age groups <3 and >3 years of age. Epiphora resolution at last office visit and restenting rate were used as outcome measures. ResultsA total of 49 patients with DS and CLNDO were identified between 2012 and 2021; of these, 17 had received surgical stent placement with appropriate follow-up. Epiphora resolution (X21= 0.78, P = 0.33), restenting rate (X21 = 2.84, P = 0.09), cumulative stent duration (P = 0.33) and number of stent placement operations (P = 0.98) were not significantly different between the age groups. There was no significant difference between stent duration <1 year or >1 year with regard to epiphora resolution (X21 = 0.91, P = 0.34). ConclusionsSuccess of stent placement and reoperation rates among patients with DS and CNLDO were not associated with age and duration of stent intubation. Intervention at later ages may still be beneficial for symptom resolution in patients with DS.

Sex-specific trisomic Dyrk1a-related skeletal phenotypes during development in a Down syndrome model.

Skeletal insufficiency affects all individuals with Down syndrome (DS) or trisomy 21 and may alter bone strength throughout development due to a reduced period of bone formation and early attainment of peak bone mass compared to those in typically developing individuals. Appendicular skeletal deficits also appear in males before females with DS. In femurs of male Ts65Dn DS model mice, cortical deficits were pronounced throughout development, but trabecular deficits and Dyrk1a overexpression were transitory until postnatal day (P) 30, when there were persistent trabecular and cortical deficits and Dyrk1a was trending toward overexpression. Correction of DS-related skeletal deficits by a purported DYRK1A inhibitor or through genetic means beginning at P21 was not effective at P30, but germline normalization of Dyrk1a improved male bone structure by P36. Trabecular and cortical deficits in female Ts65Dn mice were evident at P30 but subsided by P36, typifying periodic developmental skeletal normalizations that progressed to more prominent bone deficiencies. Sex-dependent differences in skeletal deficits with a delayed impact of trisomic Dyrk1a are important to find temporally specific treatment periods for bone and other phenotypes associated with trisomy 21.

The effect of dual-task training on postural and cognitive performances in adolescents with down syndrome

BackgroundThe dual task training (DTT) has been shown to improve postural and cognitive performances in many populations. Therefore, it seems of interest to explore the effect of such training modality in individuals with Down syndrome (DS) presenting both cognitive and postural deficits. AimsThis study explored the effect of a DTT compared to a single task training (STT) on postural and cognitive performances in adolescents with DS. Methods and proceduresThe center of pressure velocity (CoPVm) and the cognitive performance in the selective word recall test were recorded under single task (ST) and DT conditions before and after 8 weeks in the STT group (STTG), the DTTG and the control group (CG). Outcomes and resultsBefore training, CoPVm values increased and cognitive performances decreased (p < 0.001) during the DT compared to ST conditions in all groups. After training, CoPVm decreased (p < 0.001) in the DTTG and the STTG under the ST conditions. However, under DT conditions, these values decreased (p < 0.001) only in the DTTG. The cognitive performance increased (p < 0.001) only in the DTTG in both ST and DT conditions. ConclusionThe DTT is strongly recommended to improve both postural and cognitive performances in individuals with DS notably in DT conditions.

Adherence to adult clinical practice guidelines for Down syndrome.

Adults with Down syndrome (DS) have unique health care needs with evidence-based care guidelines to address these. Yet, the 2020 adult guidelines were unstudied; we aimed to assess adherence to these guidelines. We reviewed clinical and demographic data from medical charts of 327 adults with DS who were seen in the MGH DSP. We calculated adherence to care guidelines and analyzed correlations between both demographic traits and clinical results. Mean adherence rate to each of the nine adult guidelines was 67.3%. Adherence rates that were below our mean adherence rate included colonoscopy (42.9%), iron (41.9%), audiology specialist (35.8%), and audiogram (35.2%). We found four significant correlations: assigned females at birth had a significantly higher body mass index (BMI) than assigned males at birth (p < 0.001), Hispanic patients had a significantly higher BMI than other patients (p = 0.015), Hispanic patients had a significantly higher rate of diabetes than other patients (p = 0.036), and Black patients had a significantly lower rate of hypothyroidism than other patients (p = 0.004). We assessed the adherence rates to adult DS guidelines and highlighted disparities in healthcare for patients with DS to inform clinicians on how to improve care for patients with DS.

The Role of Diet and Physical Activity in Obesity and Overweight in Children with Down Syndrome in Developed Countries.

Down's syndrome (DS), or Trisomy 21, represents the most common chromosomal abnormality in live births, characterized by an extra chromosome 21. Children affected by Down's syndrome are more susceptible to the development of obesity and of becoming overweight compared with other children. Furthermore, they seem to present a more unfavorable lipid profile than the non-DS obese pediatric population. Diet and physical activity are closely related to the development of overweight and obesity, and they can be assessed using questionnaires such as the Mediterranean Diet Quality Index in children and adolescents (KIDMED) and the Godin-Shephard Leisure-Time Physical Activity Questionnaire. This review aims to undertake a comprehensive analysis of the intricate interplay between diet and physical activity in children affected by Down's syndrome. Specifically, it seeks to deepen understanding regarding the question of how diet and exercise can influence and prevent the development of overweight and obesity in that special pediatric population.

The Prevalence of Cancer Predisposition Syndromes (CPSs) in Children with a Neoplasm: A Cohort Study in a Central and Eastern European Population.

The etiology of pediatric cancers is often unclear; however, advancements in genetics have identified significant roles for genetic disorders in their development. Over time, the number of cancer predisposition syndromes (CPSs) and awareness of them have increased, providing the possibility of cancer prevention and early detection. In this study, we present data concerning the number and type of oncological cases and their correlation with CPS occurrence in a cohort of Central and Eastern European pediatric patients. The data were collected between 2000 and 2019 at the Karol Jonscher Clinical Hospital of Poznan University of Medical Sciences, resulting in a cohort of 2190 cases in total, of which 193 children (8.81%) were confirmed to have a CPS. CPSs occurred most frequently in infancy (22.90% of all children suffering from any diagnosed cancer during the first year of life; p < 0.0001), accounting for more than one-quarter of all CPS cases in our cohort. CPSs were least likely to be observed in patients aged 14 and 15 years (2.17% and 2.44% of children diagnosed with any of the listed cancers at the exact age, respectively; p < 0.05). Among CPSs, the most common were neurofibromatosis type I (NF1), Li-Fraumeni syndrome (LFS), and Down syndrome (DS). To conclude, it is important to emphasize the need for personalized treatment for each patient affected by both CPSs and subsequent cancer in order to reduce the toxicity of therapy and improve quality of life by reducing the risk of side effects.

Health comorbidities in children with down syndrome (DS) at Dr. Sardjito General Hospital, Yogyakarta

Down syndrome (DS) is a disease caused by trisomy of chromosome 21. The phenotype in DS leads to manifestations in several organ systems. This study aimed to identify the pattern of comorbidities in DS patients. It was a single-center, cross-sectional study at Dr. Sardjito General Hospital, Yogyakarta. Medical records of pediatric patients with DS from a period of January 2022 to May 2023 were included. Descriptive analysis was performed to demonstrate demographic and clinical characteristics. A total of 355 pediatric patients with DS were found at Dr. Sardjito General Hospital and the majority were male (196 children or 55.2%). As much as 339 children (95.49%) had comorbidities. The highest comorbidity was congenital heart disease (230 patients or 67.84%) in specifics were atrial septal defect (41 patients or 12.39%), atrioventricular septal defect (29 patients or 8.17%), and patent ductus arteriosus (28 patients or 7.88%). The second highest comorbidity was endocrine system disorders (102 patients or 30.09%), with 100 patients (28.16%) children suffering hypothyroidism. The number of children who had one comorbidity was 248 patients (69.86%), 74 patients (20.48%) had two comorbidities, and 17 patients (4.79%) had three or more comorbidities. The highest co-prevalence of the two comorbidities was congenital heart disease and endocrine system disorders (36 patients or 10.14%). The highest co-prevalence of 3 or more comorbidities was a combination of congenital heart disease, visual impairment, and hearing impairment (6 patients or 1.69%). In conclusion, 95.49% of children with DS have comorbidities. The most common comorbidity was heart defects. About 25.63% of patients had more than one comorbidity. Children with DS who have comorbidities require more attention to prevent complications and to reduce morbidity.

Associations of Microbleeds and Their Topography With Imaging and CSF Biomarkers of Alzheimer Pathology in Individuals With Down Syndrome.

Cerebral hemorrhages are an exclusion criterion and potential adverse effect of antiamyloid agents. It is, therefore, critical to characterize the natural history of cerebral microbleeds in populations genetically predisposed to Alzheimer disease (AD), such as Down syndrome (DS). We aimed to assess microbleed emergence in adults with DS across the AD spectrum, defining their topography and associations with clinical variables, cognitive outcomes, and fluid and neuroimaging biomarkers. This cross-sectional study included participants aged 18 years or older from the Down-Alzheimer Barcelona Neuroimaging Initiative and Sant Pau Initiative on Neurodegeneration with T1-weighted and susceptibility-weighted images. Participants underwent comprehensive assessments, including apolipoprotein E (APOE) genotyping; fluid and plasma determinations of beta-amyloid, tau, and neurofilament light; cognitive outcomes (Cambridge Cognitive Examination and modified Cued Recall Test); and vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia). We manually segmented microbleeds and characterized their topography. Associations between microbleed severity and AD biomarkers were explored using between-group comparisons (none vs 1 vs 2+) and multivariate linear models. We included 276 individuals with DS and 158 healthy euploid controls (mean age = 47.8 years, 50.92% female). Individuals with DS were more likely to have microbleeds than controls (20% vs 8.9%, p < 0.001), with more severe presentation (12% with 2+ vs 1.9%). Microbleeds increased with age (12% 20-30 years vs 60% > 60 years) and AD clinical stage (12.42% asymptomatic, 27.9% prodromal, 35.09% dementia) were more common in APOEε4 carriers (26% vs 18.3% noncarriers, p = 0.008), but not associated with vascular risk factors (p > 0.05). Microbleeds were predominantly posterior (cerebellum 33.66%; occipital 14.85%; temporal 21.29%) in participants with DS. Associations with microbleed severity were found for neuroimaging and fluid AD biomarkers, but only hippocampal volumes (standardized β = -0.18 [-0.31, -0.06], p < 0.005) and CSF p-tau-181 concentrations (β = 0.26 [0.12, 0.41], p < 0.005) survived regression controlling for age and disease stage, respectively. Microbleeds had limited effect on cognitive outcomes. In participants with DS, microbleeds present with a posterior, lobar predominance, are associated with disease severity, but do not affect cognitive performance. These results suggest an interplay between AD pathology and vascular lesions, implicating microbleeds as a risk factor limiting the use of antiamyloid agents in this population.

Drug burden index of people ageing with intellectual disability and cognitive complaints attending a specialist memory service.

Medications with sedative or anticholinergic properties should be prescribed with caution in those with cognitive complaints. This is particularly relevant in people ageing with an intellectual disability (ID). Higher drug burden index (DBI) scores are associated with increased frailty and falls and reduced quality of life in older people and increased risk of adverse effects (daytime somnolence, constipation) in those with ID. While previous studies have shown that the ID population has higher rates of drug burden and a higher propensity to be prescribed an antipsychotic than the general population, the degree of burden has not been assessed specifically in those with ID and cognitive complaints. We assessed drug burden in a cohort of sequential referrals to a national memory service for people with ID. All patients were referred for assessment of cognitive complaints (self-reported or caregiver-reported problems with memory or cognition). DBI was calculated individually for each participant, and the impact of aetiology of ID, level of ID, age, psychiatric/neurological comorbidities and diagnostic outcome on DBI scores was assessed. The study population was 58.6% female with a median age of 55years and aetiology of ID was Down syndrome (DS) in 71.3%. Consensus diagnosis was Alzheimer's dementia in 40.2%, mild cognitive impairment in 29.9% and cognitively unimpaired from baseline in 25.3%. Medication use was high with 95.4% taking medications, with a median number of medications of 4 (interquartile range 4) and a rate of polypharmacy (≥5 medications) of 51.7%. Overall, 65.5% were exposed to sedative or anticholinergic medications with 39.1% exposed to a clinically significant DBI score >1. Those with psychiatric comorbidities, non-DS aetiology or epilepsy were significantly more likely to have a DBI score >1. People with ID and incipient cognitive complaints have a high level of drug burden, which concerningly exceeds that of the general population.

Efficacy of periodontal treatment modalities in Down syndrome patients: a systematic review and meta-analysis.

The systematic review aimed to review the existing evidence, to identify and appraise the effectiveness of periodontal prevention and treatment modalities in individuals diagnosed with Down syndrome (DS) and to determine the estimates of the effects of implemented periodontal prevention and treatment strategies compared to chromosomally normal (CN) individuals. The systematic review was conducted and reported in conformity with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. The study protocol was registered in the Open Science Framework. Electronic and manual searches, in accordance with PICO framework and delineated inclusion/exclusion criteria, were conducted in multiple databases. The initial search identified 11,704 studies. After removing duplicates, 9,048 remained. Title and abstract screening narrowed these to 281 for full-text review. Ultimately, 16 studies met the inclusion criteria, with 4 eligible for quantitative data synthesis. Results of the meta-analysis indicated that professional tooth cleaning in combination with oral hygiene reinforcement was less effective in the reduction of PPD in patients with DS compared to those without DS (Mean difference (MD): 0.23; 95% Confidence Interval (CI): 0.14 to 0.32; p < 0.001). These findings suggest that conventional periodontal treatment is less effective in managing periodontitis in patients with DS. Thus, tailored periodontal care strategies that address the specific needs of individuals with DS should be implemented to improve treatment outcomes for this population The presence of moderate to high risk of bias in the included studies underscores the need for rigorously designed research that minimizes bias through effective blinding, randomization, control of confounding factors, and inclusion of diverse treatment outcomes to further investigate these associations. Based on the best available evidence, professional tooth cleaning combined with oral hygiene instructions appears to be less effective in reducing pocket depths in individuals with DS compared to those without DS. https://doi.org/10.17605/OSF.IO/UXTCG.

Informing creation of the FEEDS Toolkit to support parent-delivered interventions for eating, drinking and swallowing difficulties in young children with neurodisability: intervention use by neurodevelopmental diagnosis and healthcare professional role

BackgroundThe FEEDS (Focus on Early Eating, Drinking and Swallowing) study focused on interventions used to improve feeding for children with neurodisability and eating, drinking and swallowing difficulties (EDSD), and the...

JAK inhibition in Down Syndrome Regression Disorder

Down Syndrome Regression Disorder (DRSD) is an uncommon but devastating condition affecting primarily adolescents and young adults with Down syndrome (DS). Individuals with DS display a dysregulated immune system associated with hyperactive interferon signaling, which is associated with a high incidence of autoimmune conditions. While the cause of DSRD is unknown, increasing evidence indicates that it may have an immune basis, and some individuals with DSRD have responded to intravenous immunoglobulin therapy. This case series describes three individuals with probable DSRD who received the JAK inhibitor tofacitinib and saw improvement in DSRD symptoms across multiple domains of neurological function.

Early detection and treatment of obstructive sleep apnoea in infants with Down syndrome: a prospective, non-randomised, controlled, interventional study

Infants with Down syndrome (DS) are at high risk of obstructive sleep apnoea (OSA) which is associated with neurocognitive dysfunction and behaviour problems. The aim of our study was to evaluate the effect of early OSA treatment in infants with DS on neurocognitive development and behaviour. In this prospective, interventional, non-randomised study, 40 infants with DS underwent polysomnography (PSG) every 6 months in room air between 6 and 36 months of age (Screened Group) and were compared to a control group of 40 infants with DS receiving standard of care and a single, systematic PSG in room air at 36 months of age (Standard Care Group). When present, OSA was treated. The primary endpoint was the total score of the Griffiths Scales of Child Development, Third Edition (Griffiths III) and its subscores at 36 months. Secondary endpoints included a battery of neurocognitive and behaviour questionnaires, and PSG outcomes. On the Griffiths III, the total score was significantly higher in the Screened Group compared to the Standard Care Group (difference: 4.1; 95%CI: 1.3; 7.6; p=0.009). Results in Griffiths III subscores and secondary endpoints were in support of better neurocognitive outcomes in the Screened Group compared with the Standard Care Group. At 36 months, median (Q1; Q3) apnoea-hypopnea index was higher in the Standard Care Group (4.0 [1.5; 9.0] events/hour) compared to the Screened Group (1.0 [1.0; 3.0] events/hour, p=0.006). Moderate and severe OSA were more frequent in the Standard Care Group as compared to the Screened Group (18.9% versus 3.7% for moderate OSA and 27.0% versus 7.4% for severe OSA). Early diagnosis and treatment of OSA in infants with DS may contribute to a significantly better neurocognitive outcome and behaviour at the age of 36 months. The study was funded by the Jérôme Lejeune Foundation.

Network Pharmacology Identifies Intersection Genes of Apigenin and Naringenin in Down Syndrome as Potential Therapeutic Targets.

Down Syndrome (DS), characterized by trisomy of chromosome 21, leads to the overexpression of several genes contributing to various pathologies, including cognitive deficits and early-onset Alzheimer's disease. This study aimed to identify the intersection genes of two polyphenolic compounds, apigenin and naringenin, and their potential therapeutic targets in DS using network pharmacology. Key proteins implicated in DS, comprising DYRK1A, APP, CBS, and ETS2, were selected for molecular docking and dynamics simulations to assess the binding affinities and stability of the protein-ligand interactions. Molecular docking revealed that naringenin exhibited the highest binding affinity to DYRK1A with a score of -9.3 kcal/mol, followed by CBS, APP, and ETS2. Moreover, molecular docking studies included positive control drugs, such as lamellarin D, valiltramiprosate, benserazide, and TK216, which exhibited binding affinities ranging from -5.5 to -8.9 kcal/mol. Apigenin showed strong binding to APP with a score of -8.8 kcal/mol, suggesting its potential in modulating amyloid-beta levels. These interactions were further validated through molecular dynamics simulations, demonstrating stable binding throughout the 100 ns simulation period. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses indicated minimal fluctuations, confirming the stability of the complexes. The findings suggest that apigenin and naringenin could serve as effective therapeutic agents for DS by targeting key proteins involved in its pathology. Future studies should focus on in vivo validation, clinical trials, and exploring combination therapies to fully harness the therapeutic potential of these compounds for managing DS. This study underscores the promising role of network pharmacology in identifying novel therapeutic targets and agents for complex disorders like DS.