DS Population Research Articles

Determining the Fitness Level of People with Down Syndrome Living in Kosovo Based on the ALPHA Protocol

Purpose: This study aimed to establish national norm values for body composition and fitness levels among individuals with Down syndrome. It also aimed to investigate gender differences in body composition features and fitness parameters, analyze the impact of the region where individuals with Down syndrome reside, and compare their fitness levels with international peers. Methods: The sample included 81 participants, 40 females (height: 146.6±4.88 cm, weight: 63.6±16.4 kg) and 41 males (height: 157.4±6.21 cm, weight: 66.8±14.8 kg). To assess the physical fitness levels of the participants with Down syndrome, a modified version of the ALPHA testing protocol was used. Findings: The results demonstrated significant gender differences (p<0.05) in body composition and fitness parameters, with males generally exhibiting better outcomes compared to females. Moreover, significant disparities (p<0.05) in body composition and fitness parameters were observed among individuals with Down syndrome residing in different regions of Kosovo. Noteworthy gender disparities exist in terms of body composition and physical fitness metrics, with male participants achieving superior results compared to their female counterparts. Furthermore, noticeable variations were observed among the regional Down syndrome centers, with participants from older centers displaying improved fitness metrics and body composition features compared to those from newly established facilities. Conclusion: Gender differences in body composition and fitness were evident, with males outperforming females, except in muscle mass. Future studies should explore fitness and health barriers in Kosovo's DS population, with a focus on improving physical activity through tailored strategies.

Blood‐based biomarkers for Alzheimer’s Disease in Down Syndrome

AbstractBackgroundPeople with DS are at high risk to develop Alzheimer’s disease dementia (AD) (Lott & Head, 2001). Predicting and monitoring decline and onset of dementia is a diagnostic challenge and of essence in daily care and support for people with DS. Behavioral and Psychological Symptoms of Dementia (BPSD) are an easily accessible tool for the prediction of dementia onset in the DS population. The BPSD‐DS II scale was developed and validated by our team to identify behavioral changes linked to AD between the last six months and pre‐existing behavior in an individual with DS (Dekker et al., 2021). This project is based on a cohort of DS individuals without AD (n = 94), with AD (n = 43), or with questionable AD (qAD) (n = 54) aged >35 years. At inclusion, the BPSD‐DS II was applied to assess AD‐linked behavioral changes, and biofluid sampling was performed as well. Changes in cerebrospinal fluid (CSF) levels of monoaminergic neurotransmitters and metabolites have been associated with BPSD in AD (Dekker et al., 2015). However, CSF sampling procedures remain difficult in DS, illustrating the need for blood biomarkers. BPSD‐DS II results will be correlated with the serum levels of monoaminergic and classical AD biomarkers. Three years post‐inclusion, a follow‐up study was conducted to assess the evolution of possible AD dementia within this group and to determine the predictive values of the BPSD‐DS II scale and the different analytes.MethodWe will use reversed‐phase ultra‐high performance liquid chromatography with electrochemical detection to determine the levels of (nor)epinephrine, dopamine, serotonin and their metabolic products in serum. We will use the Simoaâ platform on the serum of clients with DS without or with (q)AD to detect the levels of Ab40, Ab42, total tau, phosphorylated tau, Glial Fibrillary Acidic Protein and Neurofilament Light chain.ResultWe expect a correlation between the results of the BPSD‐DS II and the levels of the monoamines and classical biomarkers in patients with DS without or with (q)AD.ConclusionThe diagnosis predicted by the results of the BPSD‐DS II correlates with the levels of monoamines and classical biomarkers in individuals with DS without or with (q)AD.

Longitudinal white matter hyperintensities in Down’s syndrome

AbstractBackgroundDown’s syndrome (DS) is a genetically determined form of Alzheimer’s disease (AD). Typically not complicated by systemic vascular risk factors, the DS population represents a unique opportunity to unravel the complex relationship between AD and cerebrovascular disease. Here, we aim at studying the evolution over time of white matter hyperintensities (WMHs), a key hallmark of cerebrovascular disease frequently found in AD, and to assess their topographical progression and associations with AD biomarkers in adults with DS.MethodThis longitudinal study included 43 DS adults (age = 39.8±10.4y; females = 41.9%; n = 37 asymptomatic AD, n = 6 symptomatic AD) and 81 euploid controls (age = 53.7±6.2y; females = 67.3%) from the Down‐Alzheimer Barcelona Neuroimaging Initiative, with at least 2 MRI visits with T1 and FLAIR acquisitions (time delay = 3.4±1.6y). WMHs were segmented using the Lesion Prediction Algorithm implemented in the Lesion Segmentation Toolbox (SPM12). WMH volumes were extracted in 36 regions of interest and used to compute total and regional annual volume changes. Non‐parametric statistical tests were performed to assess the effect of disease severity on WMH volume changes over time and define associations between longitudinal WMHs and baseline demographic and genetic data, and fluid biomarkers.ResultTotal annual WMH volume change increased in symptomatic DS compared to both asymptomatic DS and controls (Figure 1A). Regionally, WMH load increased in regions showing WMH at baseline in all groups (Figure 2). These changes were greater and more distributed, involving layers more distant from the ventricles (especially in occipito‐parietal regions) in symptomatic DS. Age, but not sex, intellectual disability, or APOEε4 status, was associated with longitudinal WMH in DS (Figure 1B‐F): the annual WMH volume changes in DS differed from controls at age ∼45y. Finally, WMH volume changes were negatively related to CSF‐Aβ42/40 and positively related to plasma and CSF ptau‐181 and neurofilament light (Figure 3).ConclusionPathological increases in WMH volume start ∼10 years before the mean age at onset for AD (53.8y) in DS and relate to underlying AD pathology and neurodegeneration. Regional analyses suggest that WMH volume changes increase with disease progression and progressively involve deeper white matter areas. Together, these results support that WMHs are tightly related to AD pathogenesis.

An accelerated rate of Beta‐amyloid Measured with [C‐11]PiB in Down Syndrome compared to Neurotypical Populations

AbstractBackgroundDown syndrome (DS) is characterized by a higher risk and earlier onset of beta‐amyloid (Aβ) plaque accumulation and Alzheimer’s disease (AD). The triplication of chromosome 21 containing the amyloid precursor protein (APP) gene is implicated in this process and in this study we compare the accumulation rates of Aβ between DS and neurotypical (NT) populations quantified by longitudinal [C‐11]PiB imaged at the same site to minimize experimental variation.MethodsIndividuals with three or more [C‐11]PiB scans spanning eleven years our site with at least one Aβ+ (global SUVR>1.40) and Aβ‐ [C‐11]PiB scan were selected. 12 of 74 DS and 15 of 246 NT participants fit these criteria. An identical imaging procedure was conducted for all participants imaged on either an ECAT HR+ or Biograph mCT PET scanner 50‐70 minutes post‐injection. Reconstructed PET images were summed and spatially normalized into template space and converted into 50‐70min SUVR images using a cerebellar grey matter reference region. Global SUVR composed of grey matter regions from the AAL atlas was used as a metric for Aβ deposition. SUVR data were fit against age with a logistic growth curve (f(t) = NS+K/(1+e(‐r(t‐t50)))) to determine Aβ accumulation as subjects transitioned to Aβ+. The rate of accumulation was found using the slope of the curve at Aβ positivity threshold based on the model fit. Our model fixed NS = 1.12, the average baseline SUVR of all Aβ‐ subject scans (n = 491), and K = 1.28, the highest specific binding in any participant.ResultsPlotting [C‐11]PiB SUVR against age provides visual comparisons of cohorts (Fig 1) and transforming the x‐axis to amyloid chronicity (t = 0 at Aβ+) illustrates differences in accumulation rates between groups (Fig 2). The average rate of amyloid accumulation (ΔSUVR/yr) when becoming Aβ+ in the DS cohort is 0.071(0.021) versus 0.043(0.009) for NT (p = 4.31×10−4).ConclusionsAβ accumulation rate was higher in the DS cohort compared to NT. This is consistent with the additional APP gene copy in DS, and we observed an accumulation rate 65% faster in this cohort. There was a higher variability in the DS population requiring further investigation towards understanding the influence of genetic and lifestyle factors on Aβ deposition.

P-739 High-throughput Single-cell Survey Reveal a Pathological Niche in Developing Down Syndrome Testis

Abstract Study question What are the characteristics of developing testes in DS, and how do these alterations affect gamete development and androgen production? Summary answer Molecular alterations start accumulating in every cell-type of DS fetal testis. Different cell components, compromised functions, and deviated cellular communications make up a pathological niche. What is known already DS is the most common genetic chromosomal disorder. The flat or slightly decreased live birth and the significantly prolonged lifespan contribute to a growing DS population. Their needs for reproductive care come into view. Reproductive health is crucial for spermatogenesis, male characteristics, and even brain behaviors. DS males experience normal puberty, but their sex hormones and associated gonadotropins have altered since the infant, implying testis niche cell dysfunction. Male infertility may result from germ cell and/or niche cell malfunction. A single-cell resolution survey could help thoroughly uncover the heterogeneity of DS by cell type. Study design, size, duration We applied high-throughput single-cell RNA sequencing to capture the transcriptomes of DS testis (n = 1). In parallel, testis collected from the fetus reported no genetic disorders were set as control (n = 1). Molecular and histological verifications were conducted with independent samples (3 versus 3). Samples enrolled were around 22 weeks of gestation. Participants/materials, setting, methods With ethics approval and informed consent obtainment, DS and control samples were included. DS fetus was confirmed with amniocentesis, while no genetic abnormality was reported during the prenatal examination of the diploid fetus. Single-cell RNA sequencing was conducted with the Micro-well platform, pseudotime trajectory analysis, cellular interaction analysis, and weighted gene co-expression network analysis were performed. Transmission electron microscopy, immunohistochemistry, Westerns, and qPCR were used to verify the main differences. Main results and the role of chance A total of 15349 cell transcriptomes, DS and control pooled, were compared and clustered. Major cell types were unabridged in both karyotypes. DS testis contains more Sertoli cells with an atypical expression profile, and more immune cells. DS cells exhibit a much higher level of ribosomal protein (RP genes and a significantlylower level of marker genes for each cell type, such as INSL3 for DS Leydig cell and PECAM1 for DS endothelial cell, etc. Corresponding to cell proportion difference, gene co-expression network and intercellular communication analysis also suggested an immune activation in DS. Furthermore, pseudotime analysis suggested a relative retardation and malfunction of DS cells. The main differences in gene expression were further verified. Cell proportion alteration was demonstrated with immunohistochemistry. Overwhelming RPs were shown by transmission electron microscopy. Western and qPCR were used to test the expression difference of RPs, cell-type specific functional genes, etc. Limitations, reasons for caution The sample size was limited, although verification experiments were applied with independent samples might increase the credibility. The sample size needs to be extended further. More precise molecular mechanisms of these alterations and clinical dysfunction remains to be elucidate. Wider implications of the findings This study described human fetal DS testis at single-cell level. It reveals a pathological niche of altered cell components, compromised cell function, and activated immune response. It provides further targets for complement and/or intervention to rescue the reproductive function and even improve brain behavior in DS patients, soon after birth. Trial registration number Not applicable

Beta‐amyloid plaque accumulation comparison in down syndrome and non‐down syndrome cohorts

AbstractBackgroundDown syndrome (DS) is characterized by earlier beta‐amyloid (Aβ) plaque accumulation and an increased prevalence of Alzheimer’s disease (AD) due to trisomy 21 and triplication of the amyloid precursor protein (APP) gene. While the age of AD onset is earlier in DS, AD pathology progression in non‐DS populations follows similar trends to the DS cohort. This study compares the accumulation rate of Aβ between DS and non‐DS populations measured with [C‐11]PiB at same site using the same scanning procedures.MethodsIndividuals with at least one Aβ+ [C‐11]PiB scan (Global SUVR>1.40), and at least one Aβ‐ scan from our site at the University of Wisconsin were selected for this study. 12 out of 58 DS participants in the Neurodegeneration in Aging DS (NiAD) study and 14 out of 246 non‐DS subjects from the PREDICT study fit this criteria. All images were collected on an ECAT HR+ scanner from 50‐70 minutes injection (i.d. = 15mCi). Reconstructed PET images were aligned and summed before being normalized into MNI‐152 space and converted into an SUVR image using cerebellar grey matter as a reference region. We determined rate of Aβ accumulation as the change in global SUVR per year, defined as the average of grey matter regions in the anterior cingulate, frontal cortex, parietal cortex, precuneus, temporal cortex, and striatum, and focused on the period when participants became Aβ+.ResultsPlotting global [C‐11]PiB SUVR and age (Fig 1) there is no age overlap between the two groups. The average rate of amyloid accumulation per year when becoming Aβ+ in the DS group was 0.058±0.026 compared to 0.059±0.028 for the non‐DS sample. The two groups have notably similar mean values, although when organized into box plots (Fig 2), the interquartile range of the DS subjects is 0.044 compared to a tighter 0.019 for non‐DS.ConclusionsThe pattern of Aβ accumulation in DS and non‐DS groups becoming Aβ+ have similar distributions. While we might expect a higher rate in the DS population due to the additional APP gene, our findings do not support this hypothesis. However, considerable variability in the rate of accumulation is observed requiring further investigation towards understanding this process.

352 Prevalence and Charactersitics of Moyamoya Syndrome in Patients With Down Syndrome

INTRODUCTION: Moyamoya arteriopathy can be idiopathic (moyamoya disease, MMD) or associated with other diseases, i.e., Down syndrome (moyamoya syndrome, MMS). The prevalence of Down syndrome in patients admitted for moyamoya has been estimated using the National Inpatient Sample to be 3.8%. However, the prevalence of moyamoya in Down Syndrome is not well-quantified. METHODS: This retrospective study used the Sie Center for Down Syndrome and Stroke Program databases at Children’s Hospital Colorado to identify moyamoya patients aged 30 days to 18 years at diagnosis. Demographics, clinical presentation, treatment, and outcome were compared among patients with DS, those with idiopathic MMD, and the entire group. RESULTS: Sixty-five patients (30 idiopathic, 14 MMS with DS, 21 MMS without DS). Prevalence of MMS in the DS population was 0.4%. Gender and age at presentation did not differ significantly between populations. 47% of idiopathic moyamoya patients initially presented with transient ischemic attacks (TIAs) versus 14% of DS patients (P < 0.05). This is compared to 34% of the total population that presented with TIAs. DS patients were more likely to present with stroke (57%) compared to idiopathic (37%) and total patient populations (40%) although these results were not significant. 23% of idiopathic patients presented with basal ganglia strokes compared to 7% in the DS population (P < 0.05). CONCLUSIONS: In this study, the prevalence of moyamoya in DS was 0.4%. Patients with DS were less likely to present with TIAs and more likely to present with stroke, with different stroke locations, than were other moyamoya populations.

Determinants of hand function in children and adolescent with Down Syndrome-A scoping review

BackgroundDown Syndrome (DS) is a genetic condition. Physical characteristics like short stature, hypotonia, small, and thick hands result in decreased grip and pinch strength and quality of fine motor tasks. PurposeThe purpose of this review is to summarize the evidence of upper extremity physical characteristics and its influence on hand function in DS population. Study DesignA scoping review. MethodologyA comprehensive electronic literature search was conducted through PubMed, CINAHL, Cochrane Library. The search was limited to articles written in English and published between 2010 to 2021. Additionally, books were referred for a better understanding of the hand function in DS. The Preferred Reporting Items for Systematic Review and Meta-Analysis extension for scoping reviews (PRISMA-ScR) was adopted to develop the protocol. ResultsFollowing a detailed review of 28 articles meeting the inclusion criteria, fetuses with a diagnosis of DS are reported to have shortening of humerus on sonographic markers wherein 9% of fetuses had below 5th percentile shortening. Additionally, literature reports that during reaching there was increased trunk rotation (effect size = 0.88). DS population had 60% less grip strength, 33% less palmar pinch strength ,20% less key pinch strength and poor manual dexterity (CI = 4.5-5.5). ConclusionFindings of this review concludes that physical characteristics of the upper extremity have an influence on hand function performance in children and adolescents with DS.However, only arm length and hand span have been quantified and correlated with grip strength. Further work must focus on correlation of upper extremity anthropometry and overall hand function in children and adolscents with DS.

Comparison of detoxification capacity between broodstock and hybrid offspring in the gills of juvenile shrimp ( Macrobrachium nipponense ): Response to chronic ammonia stress

Ammonia nitrogen is an important source of water pollution that severely limits the development of aquaculture. Macrobrachium nipponense is widely cultivated due to its delicious meat, strong reproductive ability and short reproductive cycle, but the problems caused by germplasm degradation are becoming increasingly concerning. Hybridization is an efficient means to solve this problem. In this study, the parental population, Dianshan Lake (DS) and the hybrid population, DS ♀ × CD (Changjiang, CJ ♂ × Dongting, DT ♀ [SCD]) were exposed to 0, 1 or 10 mg/L total ammonia nitrogen (TAN) for 28 days. Our results indicated that the number of gill-positive cells and the apoptosis rate of the two groups showed an upward trend with the ammonia nitrogen concentration increased. The ammonia metabolism-related substance levels and the detoxifying enzyme activities in the gills of shrimp in the SCD group exposed to 10 mg/L of TAN were significantly higher than shrimp in the DS group (p < 0.05). As the TAN concentration increased, the respiratory-related genes displayed a downward trend and the nitrogen metabolism-related genes presented an upward trend. Our results suggest that the SCD population had a stronger detoxifying capacity and a greater stress resistance ability than the DS population when subjected to the same concentration of ammonia nitrogen stress.

Sex Differences and Cardiovascular Diseases in Down Syndrome

Congenital heart disease and cardiovascular disease are the leading causes of death for individuals with Down Syndrome (Ds) (Zhu, J.L., et al, 2013). A systematic review was conducted in June 2021 to address the research question “Are there reported sex differences for cardiovascular disease and cardiovascular physiological function in Ds”. Since there are significant sex differences in the risk of congenital heart and cerebrovascular disease in the general population, we hypothesized that these differences are present in the Ds population. Four domains were developed: congenital heart disease, baseline physiology and risk factors, heart disease and hypertension, and cerebrovascular disease. Exclusion criteria were applied to identify studies that addressed sex differences. The systematic review shows that women with Ds have a higher rate of congenital heart disease, coronary and cerebrovascular events and Moyamoya. Following the systematic review, a retrospective medical chart review of the University of Iowa Hospitals and Clinics was conducted using the platform TriNetX to identify the incidence of congenital and cardiovascular diseases in males and females. Relative risk was computed comparing Ds to general patient counts as well as men and women within each population. Ds patients did not share most of the sex differences in risk factors observed in the general population, however there are important sex differences in each domain that may contribute to earlier mortality in women with Ds. Several studies report women have an increased probability of developing risk factors for cardiovascular disease, such as obesity. Therefore, future research to understand the mechanism underlying these sex differences is necessary.ReferencesZhu, J.L., et al., Survival among people with Down syndrome: a nationwide population‐basedstudy in Denmark. Genetics in Medicine, 2013. 15(1): p. 64‐69.

Feasibility and Long-Term Compliance to Continuous Positive Airway Pressure Treatment in Adults With Down Syndrome, a Genetic Form of Alzheimer's Disease.

BackgroundDown syndrome (DS) is a genetic form of Alzheimer’s disease (AD) with a high prevalence of obstructive sleep apnea (OSA). These characteristics place the DS population as an optimal model to study the relationship between sleep and AD and to design clinical trials of preventive sleep therapies for AD. Regrettably, OSA treatment with continuous positive airway pressure (CPAP) is often neglected in adults with DS. In both clinical practice and research trials, it is usually presumed that these patients will not adapt to or tolerate the therapy.Study ObjectiveWe aimed to evaluate the feasibility and long-term CPAP compliance in this population and their capacity to be enrolled in CPAP research studies.MethodsWe prospectively compared the CPAP compliance of 17 OSA patients with DS and 19 age and sex matched OSA euploid patients. CPAP management and follow-up schedules were prescribed according to the habitual clinical practice. We compared group differences in tolerance, objective, and subjective hours of nightly CPAP usage at the 1st, 3rd, 6th, 12th, 24th, and 36th month visits. Good compliance was defined as at least 4 h use per night. We also investigated predictive factors of long-term CPAP compliance.ResultsThe percentage of DS subjects with good CPAP compliance (81.2 vs. 78.9%) and the objective CPAP use (5 vs. 6 h, p = 0.92) did not differ from the control group (CG). Subjective CPAP compliance was significantly higher in OSA patients with DS than in controls in all the follow-up visits (8 vs. 6.75 h, p = 0.001). The DS group had a significantly higher number of visits (9 vs. 5; p = 0.021) and mask changes (2.5 vs. 2; p = 0.05) than controls. Objective hours of CPAP use at the first follow-up visit predicted long-term CPAP compliance (p < 0.005).ConclusionCPAP treatment is feasible and has good long-term compliance in OSA patients with DS. It should be recommended to improve health and prevent comorbidities. The DS population is indeed suitable to participate in longitudinal preventive sleep clinical trials for AD.

Comparison of lipid metabolism between broodstock and hybrid offspring in the hepatopancreas of juvenile shrimp (Macrobrachium nipponense): Response to chronic ammonia stress.

Ammonia nitrogen is a major pollutant that causes great physiological harm to crustaceans in culture. In this study, we conducted a 28 day chronic ammonia nitrogen stress experiment with broodstock populations (Dianshan, DS) and hybrid offspring populations (DS ♀ × CD (Changjiang ♂ × Dongting ♀), SCD) exposed to 0, 1 and 10mg/L of ammonia concentrations. A 28 day feeding trial and chronic ammonia nitrogen stress were used to investigate the effects on the growth performance, histological structure and lipid metabolism of juvenile shrimp, Macrobrachium nipponense. Our results indicated that survival rates in the SCD groups were significantly higher than those in the DS groups, whereas weight and length gain rates were not significantly different between the groups (p > 0.05). Histological structure results showed that the number of vacuoles in the DS group was significantly higher than that in the SCD group and hepatopancreas cell structures were disrupted in the ammonia treatment groups. The results of oil red staining showed that the number of lipid droplets increased significantly with the increase in ammonia concentration. As the ammonia concentration increased, fatty acid contents, lipid enzyme activities and lipid metabolism-related gene expression all tended to rise. In conclusion, ammonia nitrogen exposure caused damage to the hepatopancreas structure of juvenile shrimp and disturbed the lipid metabolism of the hepatopancreas. In addition, the SCD population had stronger stress resistance than the DS population when subjected to the same concentration of ammonia nitrogen stress.

The auditory mismatch negativity reflects accelerated aging in adults with Down’s syndrome

AbstractBackgroundAlzheimer’s disease (AD) affects nearly the entirety of the Down’s Syndrome population (DS) with a prevalence of 75% by the time they reach their 60s. The early symptoms of dementia in DS may reflect frontal lobe vulnerability to amyloid deposition. The Mismatch Negativity (MMN) is a frontocentral event‐related potential (ERP) component elicited by auditory violations. Predictive coding postulates that the brain creates neural predictions about future events by compiling statistical regularities from incoming stimuli. Within the MMN network, the MMN results from the failure of higher frontotemporal nodes to predict the incoming sensory input, which results in changes of coupling between the sensory and the frontotemporal cortices. In the typically developing (TD) population, the MMN response has been found to decrease with age. With a cross‐sectional and longitudinal study, we assessed whether the MMN reflects premature neurological aging in DS and whether it predicts cognitive decline one year later.MethodThe MMN ERP and the MMN Global‐Field Power (GFP) were elicited with an auditory global‐local task and recorded with high‐density EEG in 36 DS adults and in 39 age‐matched TD controls. Cognitive impairment was measured in DS with the neuropsychological battery CAMCOG‐DS. One year later, 34 adults with DS underwent a follow‐up administration of the CAMCOG‐DS. Linear models tested whether the MMN predicted age in the two groups. Linear and curvilinear models tested whether the MMN obtained at the first time‐point was predictive of cognitive decline one year later as measured by changes in CAMCOG‐DS scores.ResultIn the cross sectional phase, an interaction between the MMN amplitude, both expressed in ERP and GFP, and group was found. In particular, MMN amplitude predicted age in DS but not in TD. On the other hand, neither amplitude nor latency of the MMN predicted cognitive decline one year later.ConclusionOur study shows that in our cohort the MMN amplitude reflects accelerated aging in DS but not in TD, suggesting that MMN amplitude may be a sensitive marker of early onset AD in the DS population. On the other hand, neither MMN amplitude or latency predicts cognitive decline one year later.

Dental Caries Experience among Down's Syndrome Population in Saudi Arabia - A Systematic Review.

It is the most common and best-known chromosomal disorder in humans. Its incidence in Saudi Arabia is reported to be 1 in 554 live births. and the scientific evidence on the experience of dental caries (Dental Caries) in DS population is non-conclusive. The aim of this systematic review was to report on the Dental Caries experience among DS population in Saudi Arabia. The electronic databases were searched for scientific research articles published from January 2000 to July 2020. The data search was performed in the electronic search engines like PubMed, Google scholar, Scopus, Web of science, Medline, Embase, Cochrane, and Saudi Digital Library. Eight studies which met the eligibility criteria were further analyzed. The qualitative and quantative data were included in the analysis. The sample size of the study population in the included studies varied from 36 to 224 participants and their age ranged from 3 years to 40 years. In this systematic review we found that five studies have reported a higher prevalence of Dental Caries among the DS population. Three studies reported that there was no difference in the Dental Caries prevalence among the DS population when compared to those without DS. The findings of these studies emphasizes the need to prioritize preventive and curative programs for this special care group. Oral health education programs should focus on targeting the DS population as well as their caretakers in order to help them in achieving better quality of life.

Co-occurring Down Syndrome and Autism Spectrum Disorder: Cognitive, Adaptive, and Behavioral Characteristics.

The current study explores functioning in individuals with co-occurring Autism Spectrum Disorder and Down Syndrome (ASD+DS; n = 23), individuals with ASD and cognitive impairment (ASD+ID; n = 99) and individuals with idiopathic ID (n = 38). ANCOVA results revealed that individuals with ASD+DS showed strengths in behavioral functioning compared to individuals with ID and more similar behavioral functioning to those with ASD+ID (η2 = 0.12), with the exception of disruptive behaviors. Cognitive functioning (ɸc = 0.41) and ASD symptomatology (η2 = 0.11) were more comparable for children with ASD+DS and ASD + ID than for individuals with ID. Individuals with ASD+DS had the lowest overall adaptive skills (η2 = 0.11). Findings highlight similarities between ASD+DS and ASD+ID groups, emphasizing the importance of ASD identification within the DS population to provide access to specific interventions.

Percutaneous Enteral Feeding in Patients With 22q11.2 Deletion Syndrome

To describe the incidence of percutaneous enteral feeding in patients with 22q11.2 deletion syndrome (22q11.2 DS) and determine factors associated with the need for percutaneous enteral feeding tube placement. Retrospective chart review. The records of a 22q11.2 DS clinic and pediatric otolaryngology clinic at a tertiary pediatric hospital were reviewed from January 1, 2009, to December 31, 2019. All patients with confirmed 22q11.2 deletion were identified. Cardiac, otolaryngological, and feeding characteristics were recorded along with surgical history. A patient was defined to have a G-tube if the history was significant for any percutaneous gastric feeding tube placement, including a gastrostomy tube, gastrostomyjejunostomy tube, or a Mickey button. One hundred ninety patients with confirmed 22q11.2 DS by genetic testing were included. Thirty-three percent (n = 63) required G-tube placement. G-tube placement was associated with cardiac diagnosis (P < .01), history of cardiac surgery (P < .01), aspiration (P < .01), nasopharyngeal reflux (P < .01), subglottic stenosis (P < .01), laryngeal web (P = .003), and tracheostomy (P < .01). This suggests these conditions are associated with higher rates of G-tube placement in the 22q11.2 DS population. Patients with 22q11.2 DS often require supplemental nutritional support in the form of G-tube feeding, most often in the first year of life. Congenital heart abnormalities and surgery along with tracheostomy, subglottic stenosis, laryngeal web, aspiration, and nasopharyngeal reflux are significantly associated with the need for G-tube placement. Understanding associations between comorbid conditions and G-tube placement, especially those involving the head and neck, may assist with counseling of patients with 22q11.2 DS.

The Population Prevalence, Associations of Congenital Heart Defect and Mortality Risk for Down's Syndrome in South Korea Based on National Health Insurance Service (NHIS) Data.

BackgroundIn the present study, we estimated the population prevalence, associations of congenital heart defect (CHD) and mortality risk for DS using data from National Health Insurance Service (NHIS) and Rare Diseases Registry (RDR).MethodsWe collected data on subjects with DS who were registered in the RDR between 2010 and 2015. To estimate associations of CHD and mortality risk of DS, the data of DS subjects were compared with 1:5 age- and sex-matched controls.ResultsIn 2015, 2077 individuals with DS were identified out of the total population of 51,574,044 South Koreans and the prevalence was 4.03 per 100,000 persons. The trend of DS population prevalence across 10-year-old intervals showed a peak in the group under the age of 10 years (26.0 per 100,000 persons) and then declined sharply after the age of 20 years (0.98 per 100,000 persons at 30–39 years of age). In subjects with DS, the frequencies of atrial septal defect [odds ratios (OR) =65.9; 95% CI, 84.1–99.1], ventricular septal defect (OR = 88.1, 95% CI, 57.9–134.1), patent ductus arteriosus (OR = 56.9, 95% CI, 40.1–80.8), tetralogy of fallot (OR = 42.1, 95% CI, 19.3–92.3), or atrioventricular septal defect (OR = 510.0, 95% CI, 126.7–999.0) were higher than those of age- and sex-matched controls. The risk of death in patients with DS was significantly higher than that of age- and sex-matched controls [hazard ratio (HR) =41.7, 95% CI 20.0–87.0].ConclusionIn South Korea, the DS population prevalence was 4.03 per 100,000 persons in 2015. The subjects with DS were more likely to accompany CHD and have higher mortality risk than healthy controls.

The Search for Biomarkers of Alzheimer's Disease in Down Syndrome.

Adults with Down syndrome are at high risk for Alzheimer's disease (AD), with most individuals developing clinical dementia by their late 60s. This increased risk for AD has been attributed, at least in part, to triplication and overexpression of the gene for amyloid precursor protein (APP) on chromosome 21, leading to elevated levels of amyloid β peptides. This article offers a brief overview of our current knowledge of AD in the DS population. In addition, information on a NIA/NICHD-funded, multicenter longitudinal study of biomarkers of AD in adults with DS is provided.

Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion.

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n=35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj=6.73×10−6). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.

Use of recombinant human bone morphogenetic protein for revision cervical spine fusion in children with Down syndrome: a case series.

Patients with trisomy 21 (Down syndrome; DS) often have atlantoaxial instability (AAI), which, if severe, causes myelopathy and neurological deterioration. Children with DS and AAI who undergo cervical spine fusion have a high rate of nonunion requiring revision surgery. Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a TGF-β growth factor that is used to induce bone formation in spine fusion. Although previous studies in the adult population have reported no reduction in pseudarthrosis rates with the use of rhBMP-2, there is a lack of literature in the pediatric DS population. This study describes the use of rhBMP-2 in children with DS and AAI during revision to treat nonunion. A retrospective review of a cervical spine fusion database (n = 175) was conducted. This database included all cervical spine fusions using modern instrumentation at the authors' institution from 2002 to 2019. Patients with DS who underwent a revision utilizing rhBMP-2 were included in the study. The number of prior fusions, use of rhBMP-2 in fusions, length of stay, halo use, and surgical data were collected. Postoperative complications and length of follow-up were also recorded. Eight patients (75% female) met the inclusion criteria. The average age at revision with rhBMP-2 was 11 years (range 3-19 years). All patients were diagnosed with nonunion after an initial cervical fusion. All revisions were posterior fusions of C1-2 (n = 2) or occiput to cervical (n = 6). All revisions included implant revisions, iliac crest bone grafting, and rhBMP-2 use. One patient required irrigation and debridement of an rhBMP-induced seroma. Another patient required return to the operating room to repair a dural tear. There were no neurological, infectious, airway, or implant-related complications. Revision utilizing rhBMP-2 achieved fusion in 100% (n = 8) of patients. The average length of follow-up was 42.6 months. All patients demonstrated solid fusion mass on the last radiograph. This is the first case series reporting the successful use of rhBMP-2 to facilitate cervical spine fusion in patients with DS after previous nonunion. In addition, few rhBMP-2-related postoperative complications occurred.