Persistent omphalomesenteric duct in an infant with trisomy 21.

We present the case of a term newborn with trisomy 21 who presented to the paediatric emergency department with periumbilical flare and green-brown discharge from a clamped umbilical cord, initially suspected to be omphalitis. However, it was noticed later, that when the infant strained or cried, a thick, bubbling and offensive green-brown discharge came out of the clamped umbilical cord with umbilical flatus. An ultrasound abdomen and umbilical cord confirmed the presence of a persistent omphalomesenteric duct (POMD). He was then transferred to the paediatric surgical unit. There, he underwent a laparotomy and surgical resection of the POMD and was discharged home 2 days later.

SARS-CoV-2 Infection Increases High Risk Rate of Down Syndrome Screening Test by Reducing Alpha-Fetoprotein.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a significant global health issue in recent years. Numerous studies indicate that COVID-19 during pregnancy is associated with an increased likelihood of pregnancy complications. Additionally, pregnancy itself is known to elevate the risk of severe SARS-CoV-2 infection. To explore the potential impact of SARS-CoV-2 infection on the probability of Down syndrome in fetuses, we conducted serological testing of Down syndrome markers in pregnant women who had contracted the virus. METHODS: Serological experiments were conducted utilizing a particle chemiluminescence test. The cohort of pregnant women was categorized into three groups: a control group with no infection, a group infected with SARS-CoV-2 Omicron within the first six weeks of gestation, and a group infected beyond the sixth week of gestation. RESULTS: In the group of individuals infected within 6 gestational weeks, the infection resulted in a decrease in alpha-fetoprotein (AFP) levels and a higher positive rate of Down syndrome screening tests (p ˂ 0.05). However, in this study, SARS-CoV-2 infection did not lead to an increase in the occurrence of Down syndrome in the fetus. The positive rate of women infected beyond 6 gestational weeks was slightly higher than the non-infected group (6.2% vs. 5.7%), but these differences were not statistically significant (p > 0.05). Within the group infected beyond 6 gestational weeks, there was, compared to the control group, a decrease in free beta human chorionic gonadotropin (ß-hCG) levels (p < 0.05). CONCLUSIONS: This study presents a novel investigation into the impact of SARS-CoV-2 infection on AFP and ß-hCG levels. It has been observed that pregnant women who contract SARS-CoV-2 may exhibit an increased likelihood of positive results in serum tests conducted for Down syndrome screening. However, it is important to note that the occurrence of Down syndrome in the developing fetus does not appear to be elevated. To validate these findings, additional research involving larger and diverse cohorts is necessary.

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome.

Down syndrome (DS) is a genetic disease characterized by a supernumerary chromosome 21. Intellectual deficiency (ID) is one of the most prominent features of DS. Central nervous system defects lead to learning disabilities, motor and language delays, and memory impairments. At present, a prenatal treatment for the ID in DS is lacking. Subcutaneous administration of synthetic preimplantation factor (sPIF, a peptide with a range of biological functions) in a model of severe brain damage has shown neuroprotective and anti-inflammatory properties by directly targeting neurons and microglia. Here, we evaluated the effect of PIF administration during gestation and until weaning on Dp(16)1Yey mice (a mouse model of DS). Possible effects at the juvenile stage were assessed using behavioral tests and molecular and histological analyses of the brain. To test the influence of perinatal sPIF treatment at the adult stage, hippocampus-dependent memory was evaluated on postnatal day 90. Dp(16)1Yey pups showed significant behavioral impairment, with impaired neurogenesis, microglial cell activation and a low microglial cell count, and the deregulated expression of genes linked to neuroinflammation and cell cycle regulation. Treatment with sPIF restored early postnatal hippocampal neurogenesis, with beneficial effects on astrocytes, microglia, inflammation, and cell cycle markers. Moreover, treatment with sPIF restored the level of DYRK1A, a protein that is involved in cognitive impairments in DS. In line with the beneficial effects on neurogenesis, perinatal treatment with sPIF was associated with an improvement in working memory in adult Dp(16)1Yey mice. Perinatal treatment with sPIF might be an option for mitigating cognitive impairments in people with DS.

Zinc metabolism and its role in immunity status in subjects with trisomy 21: chromosomal dosage effect.

Introduction: Trisomy 21 (T21), which causes Down syndrome (DS), is the most common chromosomal aneuploidy in humankind and includes different clinical comorbidities, among which the alteration of the immune system has a heavy impact on patient's lives. A molecule with an important role in immune response is zinc and it is known that its concentration is significantly lower in children with T21. Different hypotheses were made about this metabolic alteration and one of the reasons might be the overexpression of superoxide dismutase 1 (SOD1) gene, as zinc is part of the SOD1 active enzymatic center. Methods: The aim of our work is to explore if there is a linear correlation between zinc level and immune cell levels measured in a total of 217 blood samples from subjects with T21. Furthermore, transcriptome map analyses were performed using Transcriptome Mapper (TRAM) software to investigate whether a difference in gene expression is detectable between subjects with T21 and euploid control group in tissues and cells involved in the immune response such as lymphoblastoid cells, thymus and white blood cells. Results: Our results have confirmed the literature data stating that the blood zinc level in subjects with T21 is lower compared to the general population; in addition, we report that the T21/control zinc concentration ratio is 2:3, consistent with a chromosomal dosage effect due to the presence of three copies of chromosome 21. The transcriptome map analyses showed an alteration of some gene's expression which might explain low levels of zinc in the blood. Discussion: Our data suggest that zinc level is not associated with the levels of immunity cells or proteins analyzed themselves and rather the main role of this ion might be played in altering immune cell function.

Rate and management of tympanic membrane perforations in children with Down syndrome and middle ear disorder.

OBJECTIVE: To characterize the management and outcomes of observation versus surgical intervention of tympanic membrane (TM) perforations in children with Down syndrome (DS). In addition, to estimate the prevalence of TM perforations in children with DS. METHODS: Retrospective case review analysis of TM perforation rate in children with DS with history of tympanostomy tube (TT) insertion at a tertiary pediatric referral center. Patients were divided into observation or surgical intervention groups and then further evaluated for the type of intervention, the number of required procedures, and success rate of hearing improvement. Risk factors contributing to perforations were analyzed, including TT type, number of TT surgeries, and perforation size. RESULTS: The TM perforation rate in children with DS with TT history was 7.0 %. Tympanoplasty was performed in 41.5 % of perforated ears with a success rate of 53.1 %. There was no statistical difference between the surgical intervention and observation groups regarding perforation characteristics or TT number and type, but the surgical intervention cohort was older. Hearing improvement based on postoperative pure tone average (PTA) threshold was noted in the successful surgical intervention group. CONCLUSION: The rate of TM perforations in children with DS after TTs is comparable to the general population. Improved PTA thresholds were noted in the surgical success group influencing speech development. The overall lower success rate of tympanoplasty in patients with DS emphasizes the need to factor in the timing of surgical intervention based on the predicted age of Eustachian tube maturation.

Complementary feeding practices of caregivers of infants with Down syndrome as compared to caregivers of typically developing infants.

Caregiver feeding practices during the complementary feeding period (6 months-2 years) may be particularly important for infants with Down syndrome (DS) as they are at higher risk for later health conditions (e.g., obesity, diabetes) that can be influenced by early feeding practices. However, how well caregivers of infants with DS are meeting infant feeding evidence-based practices is relatively unknown. Caregivers of infants with DS (N = 75) and caregivers of typically developing (TD) infants (N = 66) aged 0-2 years completed an online survey about their infant feeding practices and information sources. Caregiver practices and information sources were statistically compared between groups. Results indicated that there are significant differences in the feeding practices of caregivers of infants with DS when compared to caregivers of TD infants. Caregivers of infants with DS were less likely to meet infant feeding evidence-based practices than caregivers of TD infants. Caregivers of infants with DS were also more concerned about their infant's food intake and later weight status. Some individual feeding practices also significantly differed between groups, with caregivers of infants with DS more likely to meet evidence-based practices of purchasing iron rich foods and avoiding added salt, but less likely to use responsive feeding practices than caregivers of TD infants. Caregivers of infants with DS were also less likely to receive information about how to navigate the complementary feeding period than caregivers of TD infants. Coupled with existing research, the results of the present study suggest that infant feeding evidence-based practices should be reviewed for their appropriateness for this population and additional support for caregivers of infants with DS should be implemented to help them navigate this important period.

Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity.

BACKGROUND: Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer's disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved. METHODS: Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices. RESULTS: Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP. CONCLUSIONS: Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders.

Outcomes of surgical treatment of patellar instability in children with Down syndrome.

BACKGROUND: patellar instability is a relatively frequent musculoskeletal disorder in children with Down syndrome (DS). However, such a condition has seldom been studied in the literature, even less its surgical treatment. Different techniques have been offered for this condition; the evidence for surgical options is scarce and primarily based on case reports or case series with few patients and heterogeneous techniques. Given this background, we aimed to evaluate the outcomes of a uniform kind of surgical procedure for such a condition that combined lateral soft tissue release, medial patellofemoral ligament (MPFL) reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty (if needed). MATERIALS AND METHODS: This retrospective study involved 11 skeletally immature patients (12 knees; 9 males and 2 females), 5.5 to 14.1 years of age, with DS who had patellofemoral instability (PFI) and were managed by this technique between October 2018 and March 2020. Preoperative radiography, CT scan, and MRI were performed to evaluate the physis status, lower limb alignment, patellar height, trochlear morphology, and any associated knee pathology. A functional knee assessment was done by using the Kujala score and the modified Lysholm score. RESULTS: The mean time of follow-up (± SD) was 47.7 ± 5.8 months (range: 39-56). Pre-operatively, the Kujala score (± SD) was 52.6 ± 14.3 (range: (31-74), and at final follow-up, it was 92.2 ± 4.4 (range: (88-98), showing a significant improvement (P < 0.001). The preoperative modified Lysholm score (± SD) was 54.3 ± 8.1 (range: 39-62), and at final follow-up it was 92.4 ± 5.3 (range: 82-96), showing a significant improvement (P < 0.001). All patients had a stable patella without a recurrence of instability and regained full ROM. There was no incidence of a patellar fracture or femoral physis injury. CONCLUSIONS: Our proposed technique of combined soft tissue procedures, including lateral soft tissue release, MPFL reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty, was an effective method for treating patellar instability in children with DS while avoiding physeal injury and patellar fracture. Functional scores and radiological outcomes were improved. LEVEL OF EVIDENCE: IV; retrospective case series.

Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea in a Young Child With Down Syndrome.

Obstructive sleep apnea (OSA) is common in children with Down syndrome (DS). Adenoidectomy and/or tonsillectomy are the usual first interventions employed to treat OSA in children with DS but sometimes do not achieve adequate resolution of clinical signs. Positive airway pressure treatment is often used next, but this treatment is poorly tolerated by this population. Persistent OSA can adversely affect a child's health and cognitive development. Hypoglossal nerve stimulation (HGNS), previously shown to be safe and effective in adults with OSA, has been used in children as young as 10 years old with DS and has achieved measurable neurocognitive benefits. The US Food and Drug Administration recently lowered the age for HGNS implantation to 13 years for children with DS. However, questions remain regarding treatment of refractory OSA in younger children. Here, we report the case of a 4-year-old boy with DS and treatment-refractory OSA who underwent successful HGNS implantation. The decision to proceed with HGNS implantation in such a young child involved discussions about anatomic feasibility and potential neurocognitive benefits. The device was implanted without complication and with minimal postoperative bulk. This case suggests a possible treatment option that can be discussed in the course of shared decision-making between clinicians and families of young children with DS and treatment-refractory OSA.

Efecto del programa nutricional “Tusuy” en la composición corporal y bienestar emocional en personas con síndrome de Down / The effect of the “Tusuy” nutritional program on body composition and emotional well-being in people with Down syndrome

Introducción. El síndrome de Down es una condición genética que afecta física y cognitivamente al ser humano. Los programas nutricionales basados en el fomento de la actividad física mejoran la hipotonía muscular y el bienestar emocional en personas con síndrome de Down.Objetivo: Evaluar el efecto del programa nutricional “Tusuy” en la composición corporal y bienestar emocional de personas con síndrome de Down, durante ocho semanas de intervención. Material y métodos: Investigación de enfoque cuantitativo, diseño experimental, nivel pre-experimental. La muestra final fue conformada por 25 personas con síndrome de Down, con asistencia regular al taller de danza; fueron excluidos personas con diagnóstico severo de síndrome de Down. El programa nutricional Tusuy tuvo una duración de ocho semanas, que incluía el taller de danza, sesiones educativas para mejorar la alimentación y seguimiento a través de WhatsApp de los padres de familia. El perímetro abdominal se midió a través cinta métrica marca Lufkin, consignado en una ficha antropométrica; el bienestar emocional fue evaluado a través de la escala de bienestar psicológico, validada mediante juicio de expertos. Para comparar los resultados antes y después de la intervención, se utilizó la prueba estadística no paramétrica de Wilcoxon. Resultados: Antes de la intervención, al analizar el perímetro abdominal, se obtuvo 36 % en riesgo muy alto, con promedio de 91,17 ± 11,39 cm; asimismo, el 64,0 % presentó bienestar psicológico. Al término de la intervención, el 20,0 % presentó riesgo muy alto; el promedio del perímetro abdominal fue de 89,18 ± 11,84 cm; el 98,0 % presentó bienestar psicológico. Al comparar ambos grupos experimentales, se obtuvo un valor p<0,05. Conclusión: El programa nutricional “Tusuy”, que duró ocho semanas de intervención, mejoró la composición corporal y el bienestar emocional en personas con síndrome de Down.(AU)

Introduction: Down syndrome is a genetic conditionthat affects humans physically and cognitively. Nutritionalprograms based on promoting physical activity improvemuscle hypotonia and emotional well-being in people withDown syndrome. Objective: To evaluate the effect of the “Tusuy” nutri-tional program on the body composition and emotional well-being of people with Down syndrome, during eight weeks ofintervention. Material and methods:Research with a quantitative ap-proach, experimental design, pre-experimental level. The fi-nal sample was made up of 25 people with Down syndrome,with regular attendance at the dance workshop; People witha severe diagnosis of Down syndrome were excluded. TheTusuy nutritional program lasted eight weeks, which includedthe dance workshop, educational sessions to improve nutri-tion, and monitoring of parents via WhatsApp. Abdominalperimeter was measured using a Lufkin measuring tape,recorded on an anthropometric sheet; Emotional well-beingwas evaluated through the psychological well-being scale, validated through expert judgment. To compare the resultsbefore and after the intervention, the non-parametricWilcoxon statistical test was used. Results: Before the intervention, when analyzing the ab-dominal perimeter, 36% were found to be at very high risk,with an average of 91.17 ± 11.39 cm; Likewise, 64.0% pre-sented psychological well-being. At the end of the interven-tion, 20.0% presented very high risk; the average abdominalperimeter was 89.18 ± 11.84 cm; 98.0% presented psycho-logical well-being. When comparing both experimentalgroups, a p value <0.05 was obtained.Conclusion: The “Tusuy” nutritional program, which lastedeight weeks of intervention, improved body composition andemotional well-being in people with Down syndrome.(AU)

Endocrine, auxological and metabolic profile in children and adolescents with Down syndrome: from infancy to the first steps into adult life.

Down syndrome (DS) is the most common chromosomal disorder worldwide. Along with intellectual disability, endocrine disorders represent a remarkable share of the morbidities experienced by children, adolescents and young adults with DS. Auxological parameters are plotted on syndrome-specific charts, as growth rates are reduced compared to healthy age- and gender-matched peers. Furthermore, children with DS are at increased risk for thyroid dysfunctions, diabetes mellitus, osteopenia and obesity compared to general population. Additionally, male individuals with DS often show infertility, while women tend to experience menopause at an overall younger age than healthy controls. Given the recent outstanding improvements in the care of severe DS-related comorbidities, infant mortality has dramatically decreased, with a current average life expectancy exceeding 60 years. Accordingly, the awareness of the specificities of DS in this field is pivotal to timely detect endocrine dysfunctions and to undertake a prompt dedicated treatment. Notably, best practices for the screening and monitoring of pediatric endocrine disorders in DS are still controversial. In addition, specific guidelines for the management of metabolic issues along the challenging period of transitioning from pediatric to adult health care are lacking. By performing a review of published literature, we highlighted the issues specifically involving children and adolescent with DS, aiming at providing clinicians with a detailed up-to-date overview of the endocrine, metabolic and auxological disorders in this selected population, with an additional focus on the management of patients in the critical phase of the transitioning from childhood to adult care.

Analysis of Down syndrome newborn outcomes in three neonatal intensive care units in Rio de Janeiro, Brazil.

OBJECTIVE: The aim of this study was to analyze the outcomes of newborns with Down syndrome admitted to three neonatal intensive care units in the city of Rio de Janeiro, Brazil. METHODS: A retrospective cohort study was conducted by analyzing the medical records between 2014 and 2018 of newborns with Down syndrome admitted to three neonatal intensive care units. The following variables were analyzed: maternal and perinatal data, neonatal malformations, neonatal intensive care unit intercurrences, and outcomes. RESULTS: A total of 119 newborns with Down syndrome were recruited, and 112 were selected for analysis. The most common maternal age group was >35 years (72.07%), the most common type of delivery was cesarean section (83.93%), and the majority of cases were male (53.57%). The most common reasons for neonatal intensive care unit hospitalization were congenital heart disease (57.66%) and prematurity (23.21%). The most common form of feeding was a combination of human milk and formula (83.93%). The second most common malformation was duodenal atresia (9.82%). The most common complications during neonatal intensive care unit hospitalization were transient tachypnea of the newborn (63.39%), hypoglycemia (18.75%), pulmonary hypertension (7.14%), and sepsis (7.14%). The mean length of stay in the neonatal intensive care unit was 27 days. The most common outcome was discharge (82.14%). Furthermore, 12.50% of newborns were transferred to an external neonatal intensive care unit, and 6% died. CONCLUSION: Newborns with Down syndrome are more likely to be admitted to the neonatal intensive care unit, and the length of hospital stay is longer due to complications related to congenital malformations common to this syndrome and prematurity.

Revisiting Atrioventricular Septal Defects: Exploring Chromosomal Abnormalities, Cardiac and Extracardiac Anomalies in a Contemporary Prenatal Cohort.

To estimate if there is an association between partial AVSD with chromosomal abnormalities, cardiac and extracardiac malformations, and to report the outcomes of prenatally diagnosed AVSD in a large, contemporary cohort. This is a retrospective cohort study of 190 prenatally diagnosed fetal AVSD between 2014 and 2023. Type of AVSD (complete vs partial), additional cardiac findings, extracardiac findings, presence of a heterotaxy, results of prenatal karyotype, and pregnancy outcomes were documented and analyzed. A total of 190 cases of fetal AVSD were analyzed. Complete AVSDs comprised 141 (74.2%) of the cohort, while partial AVSDs comprised 49 (25.7%). Karyotype was completed in 131 cases, and in 98 (74.8%) cases chromosomal abnormalities were identified, with trisomy 21 being the most common (53/131, 40.5%). Complete AVSDs were associated with trisomy 21 (45.5%, p = 0.04), Isolated cases of complete AVSDs (p = 0.03). Partial AVSDs were associated with trisomy 18 (53.1%, p < 0.001). In cases of partial AVSDs with aneuploidies, 7 (70%) had an ostium primum defect and 20 (90.9%) of AV canal type VSD. Isolated partial AVSD had no clear association with aneuploidies. There were additional cardiac anomalies in 96 (50.5%) and extracardiac anomalies in 134 (70.5%) of the cohort. There were no differences between partial and complete AVSD in rate of additional cardiac and extracardiac anomalies. AVSD was part of a heterotaxy in 47 (24.7%) of cases, and heterotaxy was associated with complete AVSD in the majority of cases (43/47, 91.4%, p = 0.003). Fetal partial AVSDs are associated with trisomy 18. Fetal complete AVSDs, even isolated, are associated with trisomy 21. There were no differences in association of other aneuploidies, additional cardiac findings, or extracardiac anomalies between prenatally diagnosed complete AVSDs and partial AVSDs.

Advancing fetal ultrasound diagnostics: Innovative methodologies for improved accuracy in detecting down syndrome.

This research work explores the integration of medical and information technology, particularly focusing on the use of data analytics and deep learning techniques in medical image processing. Specifically, it addresses the diagnosis and prediction of fetal conditions, including Down Syndrome (DS), through the analysis of ultrasound images. Despite existing methods in image segmentation, feature extraction, and classification, there is a pressing need to enhance diagnostic accuracy. Our research delves into a comprehensive literature review and presents advanced methodologies, incorporating sophisticated deep learning architectures and data augmentation techniques to improve fetal diagnosis. Moreover, the study emphasizes the clinical significance of accurate diagnostics, detailing the training and validation process of the AI model, ensuring ethical considerations, and highlighting the potential of the model in real-world clinical settings. By pushing the boundaries of current diagnostic capabilities and emphasizing rigorous clinical validation, this research work aims to contribute significantly to medical imaging and pave the way for more precise and reliable fetal health assessments.

Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study.

BACKGROUND: In people with genetic forms of Alzheimer's disease, such as in Down syndrome and autosomal-dominant Alzheimer's disease, pathological changes specific to Alzheimer's disease (ie, accumulation of amyloid and tau) occur in the brain at a young age, when comorbidities related to ageing are not present. Studies including these cohorts could, therefore, improve our understanding of the early pathogenesis of Alzheimer's disease and be useful when designing preventive interventions targeted at disease pathology or when planning clinical trials. We compared the magnitude, spatial extent, and temporal ordering of tau spread in people with Down syndrome and autosomal-dominant Alzheimer's disease. METHODS: In this cross-sectional observational study, we included participants (aged ≥25 years) from two cohort studies. First, we collected data from the Dominantly Inherited Alzheimer's Network studies (DIAN-OBS and DIAN-TU), which include carriers of autosomal-dominant Alzheimer's disease genetic mutations and non-carrier familial controls recruited in Australia, Europe, and the USA between 2008 and 2022. Second, we collected data from the Alzheimer Biomarkers Consortium-Down Syndrome study, which includes people with Down syndrome and sibling controls recruited from the UK and USA between 2015 and 2021. Controls from the two studies were combined into a single group of familial controls. All participants had completed structural MRI and tau PET (18F-flortaucipir) imaging. We applied Gaussian mixture modelling to identify regions of high tau PET burden and regions with the earliest changes in tau binding for each cohort separately. We estimated regional tau PET burden as a function of cortical amyloid burden for both cohorts. Finally, we compared the temporal pattern of tau PET burden relative to that of amyloid. FINDINGS: We included 137 people with Down syndrome (mean age 38·5 years [SD 8·2], 74 [54%] male, and 63 [46%] female), 49 individuals with autosomal-dominant Alzheimer's disease (mean age 43·9 years [11·2], 22 [45%] male, and 27 [55%] female), and 85 familial controls, pooled from across both studies (mean age 41·5 years [12·1], 28 [33%] male, and 57 [67%] female), who satisfied the PET quality-control procedure for tau-PET imaging processing. 134 (98%) people with Down syndrome, 44 (90%) with autosomal-dominant Alzheimer's disease, and 77 (91%) controls also completed an amyloid PET scan within 3 years of tau PET imaging. Spatially, tau PET burden was observed most frequently in subcortical and medial temporal regions in people with Down syndrome, and within the medial temporal lobe in people with autosomal-dominant Alzheimer's disease. Across the brain, people with Down syndrome had greater concentrations of tau for a given level of amyloid compared with people with autosomal-dominant Alzheimer's disease. Temporally, increases in tau were more strongly associated with increases in amyloid for people with Down syndrome compared with autosomal-dominant Alzheimer's disease. INTERPRETATION: Although the general progression of amyloid followed by tau is similar for people Down syndrome and people with autosomal-dominant Alzheimer's disease, we found subtle differences in the spatial distribution, timing, and magnitude of the tau burden between these two cohorts. These differences might have important implications; differences in the temporal pattern of tau accumulation might influence the timing of drug administration in clinical trials, whereas differences in the spatial pattern and magnitude of tau burden might affect disease progression. FUNDING: None.

Homogeneity in Motor Competence Among Youths With Intellectual Disability With and Without Down Syndrome.

PURPOSE: To determine if there is a homogeneity of scores for youth with intellectual disability (ID) with and without Down syndrome (DS) in 19 test items of motor competence from the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition (BOT-2). Homogeneity was defined as the means for each of the 19 test items scores by sex and the presence or absence of DS sharing the same population mean. METHOD: Participants were 622 youth with ID aged 6 to 21 years. Items for bilateral coordination, balance, and upper limb coordination were examined using the BOT-2. RESULTS: For all 19 BOT-2 items, means between youth with and without DS did not differ from the population mean. CONCLUSION: These results potentiate the development of expected BOT-2 motor competence scores for youth with ID independent of the presence of DS for clinical practice.

Early Chronic Fluoxetine Treatment of Ts65Dn Mice Rescues Synaptic Vesicular Deficits and Prevents Aberrant Proteomic Alterations.

Down syndrome (DS) is the most common form of inherited intellectual disability caused by trisomy of chromosome 21, presenting with intellectual impairment, craniofacial abnormalities, cardiac defects, and gastrointestinal disorders. The Ts65Dn mouse model replicates many abnormalities of DS. We hypothesized that investigation of the cerebral cortex of fluoxetine-treated trisomic mice may provide proteomic signatures that identify therapeutic targets for DS. Subcellular fractionation of synaptosomes from cerebral cortices of age- and brain-area-matched samples from fluoxetine-treated vs. water-treated trisomic and euploid male mice were subjected to HPLC-tandem mass spectrometry. Analysis of the data revealed enrichment of trisomic risk genes that participate in regulation of synaptic vesicular traffic, pre-synaptic and post-synaptic development, and mitochondrial energy pathways during early brain development. Proteomic analysis of trisomic synaptic fractions revealed significant downregulation of proteins involved in synaptic vesicular traffic, including vesicular endocytosis (CLTA, CLTB, CLTC), synaptic assembly and maturation (EXOC1, EXOC3, EXOC8), anterograde axonal transport (EXOC1), neurotransmitter transport to PSD (SACM1L), endosomal-lysosomal acidification (ROGDI, DMXL2), and synaptic signaling (NRXN1, HIP1, ITSN1, YWHAG). Additionally, trisomic proteomes revealed upregulation of several trafficking proteins, involved in vesicular exocytosis (Rab5B), synapse elimination (UBE3A), scission of endocytosis (DBN1), transport of ER in dendritic spines (MYO5A), presynaptic activity-dependent bulk endocytosis (FMR1), and NMDA receptor activity (GRIN2A). Chronic fluoxetine treatment of Ts65Dn mice rescued synaptic vesicular abnormalities and prevented abnormal proteomic changes in adult Ts65Dn mice, pointing to therapeutic targets for potential treatment of DS.

Kidney and urogenital abnormalities in Down syndrome: a meta-analysis.

BACKGROUND: Reviews on Down syndrome do not or only marginally address the issue of kidney and urogenital tract abnormalities, and lower urinary tract dysfunctions. Hence, we performed a meta-analysis of the literature.  METHODS: A literature search was undertaken in the Library of Medicine, Web of Science and Excerpta Medica. The search algorithm combined various keywords: (Down syndrome OR trisomy 21 OR mongolism) AND (kidney OR urinary tract OR bladder) AND (malformation OR dysfunction OR anomaly OR abnormality OR size). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used. RESULTS: Eight case-control studies were retained for the final analysis. Three studies addressed the prevalence of kidney and urogenital tract abnormalities: an increased pooled relative risk of 5.49 (95%-CI: 1.78-16.93) was observed in Down syndrome. Penile malformations, obstructive malformations (including urethral valves), dilated urinary tract system, and kidney hypodysplasia were especially common. Three reports addressed the prevalence of lower urinary tract dysfunction: an increased pooled relative risk of 2.95 (95%-CI: 1.15-7.56) was observed. Finally, an autoptic study and an ultrasound study disclosed a reduced kidney size in Down syndrome. CONCLUSIONS: This meta-analysis indicates that abnormalities of the kidney and urogenital tract, lower urinary tract dysfunctions, and a reduced kidney size present with an increased frequency in individuals with Down syndrome.

Parents' perceptions of morbidities and some functional abilities in people with down syndrome in Morocco.

Objective: This study aimed to assess parental perceptions of morbidity and certain functional abilities in people with Down syndrome (DS) and their variability according to age and sex in Morocco. Material and Methods: A retrospective and analytical survey was conducted between May 2014 and November 2017, and addressed to the parents of 279 individuals with DS, including 161 boys (57.7%) aged 1-40 years. The sample was subdivised to tree age groups, children under 10 years old, adolescents aged 10-18 years and adults aged ≥ 18 years. Information about the identity of parents, age and sex of people with DS, their morbidity during the two years preceding the survey, and some functional abilities was collected. Data were entered and analyzed using the statistical program SPSS statistics software for Windows (version 20.0). Chi-square (χ2) test was used for testing statistical significance. Differences were considered significant when the p-value < 0.05. The multivariate analysis were used to identify the causes of morbidies independently associated with age and sex of child. Associations were measured in Odds ratio (OR) with 95% confidence intervals (95% Cl). Results: The most common factors of morbidity registered in the study sample with DS, included respiratory infections, visual disturbances, oral pathologies, and cardiac problems (75.4%, 72.1%, 59.3%, and 44.9%, respectively). The hearing deficit, cardiac problems, respiratory infections, and oral pathologies showed statistically significant differences among the three age groups. According to the participants parents' perceptions, half of them (50%) were able to walk at 30 months, talk at 72 months, sit at 16 months, crawl at 16 months and eat alone at 48 months old. Conclusion: People with DS at different ages present a set of potentially treatable diseases that require multidisciplinary medical monitoring. They also need early paramedical care to improve their functional abilities.