Search Results (98)

Background/Objectives: Ring chromosomes (RCs) can be rare or common depending on the chromosome involved. With interest in the historical RCs identified by our laboratory, we curated instances to provide further information to this research field. Methodology: We carried out a retrospective, single-center study of constitutional RCs identified starting in the late 1980s. Details for 40 RCs with a modal number of 46 chromosomes are featured here. Results: Mosaic and non-mosaic RCs are identified, with a preponderance of pediatric-aged females at first ascertainment. We corroborated an enrichment for acrocentric and X chromosome RCs. Six were ascertained perinatally, with peripheral blood being the most commonly studied postnatal specimen type. Notable RCs included a female fetus with an increased risk for monosomy X, whose mosaic RCY arose secondary to a translocation between the sex chromosomes. In another, a series of complex events formed three structurally aberrant chromosomes, including an RC4 with loss of 4p16.3, corresponding with the observed phenotypic expression of Wolf–Hirschhorn syndrome. In another, a mosaic RCX was co-identified with an isochromosome 21q, resulting in a dual diagnosis of trisomy 21 and Turner syndrome. In another, the atypical RC21 structure raises the possibility of a complex rearrangement. Chromosomal microarray data clarified breakpoints and gene dosage imbalances in fifteen, while low-level mosaicism for the RC escaped detection by array in another. Eight RCs were de novo, and parental exclusion was documented for six. Conclusions: This study illustrates the need for cytogenomic follow-up to improve the literature for patients with RCs. Full article

Background: Food neophobia, defined as reluctance to try new foods, may lead to nutritional deficiencies and complicate dietary management—especially in individuals with Down syndrome, who often present with oral-motor dysfunction. This condition may result in nutritional deficiencies and difficulties in adhering to dietary recommendations, particularly in individuals with comorbidities. In individuals with Down syndrome (DS), who frequently present with oral motor disorders and chronic diseases, the problem may be especially pronounced. Objectives: The aim of the study was to assess the risk of food neophobia and feeding difficulties in children, adolescents, and young adults with Down syndrome, as well as their associations with age, gender, and body weight. Methods: The research was conducted using the CAWI method among 310 caregivers of individuals with DS in Poland. Two validated tools were employed: the Montreal Children’s Hospital Feeding Scale (MCH-FS) and the Food Neophobia Scale for Children (FNSC). Body mass index (BMI), comorbidities, and demographic data were also analyzed. Results: Findings revealed that the majority of participants (55.2%) had normal body weight, while 19.4% were undernourished and 6.5% were classified as obese. Feeding difficulties of moderate to very high severity were reported in 26.5% of the participants. A high risk of food neophobia was identified in 41.3% of respondents, most frequently in the preschool age group. A statistically significant association was observed between age and the severity of both feeding difficulties and neophobia (p < 0.05). However, no significant relationships were found with gender or body weight. Conclusions: Feeding difficulties and food neophobia are prevalent among individuals with Down syndrome, particularly in preschool-aged children. The findings highlight the necessity of an interdisciplinary therapeutic approach and the individualization of dietary interventions, taking developmental age into account. Further studies are warranted, with consideration of environmental and psychosocial factors. Full article

Chromosomal defects are a significant cause of perinatal death and childhood disability, occurring in 3.6–6.0 per 1000 births in unscreened populations. Common chromosomal defects include trisomy 21, 18, and 13, triploidy, and sex chromosome abnormalities. Screening for these defects began in the mid-1960s with the advent of amniocentesis, and various methods have since been developed to improve screening performance. Initial screening was based solely on maternal and gestational age, a method incorporated later into all subsequent screening methods giving an a priori background risk. This a priori background risk, which is further refined by maternal serum biochemistry, results of ultrasound examinations, and most recently, results of non-invasive prenatal testing by cell-free DNA in maternal blood. This paper will describe methods of screening for all chromosomal defects and their performance. Unlike most reviews, this paper covers not only screening tests for Down syndrome, but also screening methods for the other most common and less common chromosomal defects. Full article

Down Syndrome or Trisomy 21 (T21) is a complex genetic disease characterized by the presence of an extra chromosome 21, which leads to multiple clinical features and manifestations that severely affect the patient’s quality of life. Various methods of prenatal screening have been developed over time, allowing informed decision-making. However, a common drawback of the current methods for detecting T21 is their invasive nature. Over the past years, mass-spectrometry-based omics technologies have become a key tool for discovering biomarkers for the prenatal screening of T21, particularly focusing on proteins, peptide sequences, or metabolites in samples, like amniotic fluid, umbilical cord blood, and others. Recently, there has been a noticeable shift towards using less invasive biological sample types (e.g., maternal serum, plasma, and urine) reflecting a growing interest in non-invasive methods for prenatal screening. These advances aim to improve the sensitivity and accuracy for T21 detection while reducing the risks associated with more invasive procedures. The first section of this paper offers an in-depth review of studies utilizing mass-spectrometry-based omics for the prenatal screening of T21. This part provides an overview of the methodologies employed and their key findings. Instead, the subsequent section offers a comprehensive examination of the differentially expressed proteins (DEPs) and metabolites (DEMs) reported in the literature in T21 prenatal screening. Additionally, pathway analysis is carried out to explore the biological pathways that these molecules are involved in and how they relate to the clinical features of the syndrome. These findings aim to guide future research in the field and foster the development of more advanced, less invasive prenatal screening techniques for T21. Full article

Background/Objectives: Down syndrome (DS) is the most common chromosomal abnormality in live births in the United States. Children with DS often require anesthesia for surgery or diagnostic imaging in their lives. These children present a unique perioperative risk profile due to a combination of anatomic and physiological alterations, along with associated comorbid conditions. There are limited studies on the perioperative outcomes of children with DS. This retrospective study assesses perioperative complications in pediatric patients with DS undergoing non-cardiac surgery or diagnostic imaging under anesthesia at a single tertiary pediatric hospital. Methods: The electronic medical record at a tertiary pediatric hospital was queried for children with DS who received anesthesia for non-cardiac surgery or diagnostic imaging from May 2016 to April 2021. The primary outcomes were complications defined as readmission, reoperation, or unexpected respiratory, cardiovascular, neurologic, surgical, or gastrointestinal issues. Exclusion criteria were cardiac surgery, age > 18 years, and records with incomplete or missing data. Results: A total of 1713 anesthetic records from 711 unique patients over five years were included in the final analysis. The study found a low overall complication rate (2.98%), with respiratory events being the most common (43.1%). While most complications are short term and resolved with treatment and time; there were also several severe, life-threatening complications. Increased procedural complexity, multiple procedures, and increased procedure duration were associated with higher complication rates, whereas patient age, sex, weight, and case urgency were not associated with higher complication rates. Conclusions: Children with DS often have comorbid conditions and require multiple life-improving surgeries. Our study found the perioperative complication rate for children with Down syndrome receiving anesthesia for non-cardiac surgery or diagnostic imaging is low, comparable to the general pediatric population. The findings indicate that anesthesia is well tolerated by children with DS. However, given patients’ unique anatomic and physiological differences, careful perioperative risk assessment and planning is essential. Clinical Implications: (a) What is already known about the topic: Pediatric patients with DS often require anesthesia for surgical procedures or medical imaging. They have anatomic and physiological alterations and comorbid conditions that may influence perioperative risk. (b) What new information this study adds: In a retrospective study at a tertiary pediatric hospital, patients with DS were found to have a low overall complication rate after anesthesia for non-cardiac surgery or diagnostic imaging. Increased procedural complexity, multiple procedures, and increased procedure duration were associated with higher complication rates. Full article

Background/Objectives: Atlantoaxial instability (AAI) affects approximately 20% of individuals with Trisomy 21. Radiological screening has been debated for decades due to its unclear clinical utility and lack of standardized diagnostic criteria. This systematic review evaluates the indications, efficacy, and clinical implications of radiological screening for AAI in children with Trisomy 21. Methods: Following the PRISMA guidelines, we conducted a systematic search in PubMed, Embase, and Google Scholar for studies published between 1990 and May 2024. Studies were included if they assessed AAI screening in pediatric Trisomy 21 populations, defined AAI radiologically, and reported at least two cases. We extracted the demographic data, study design, radiological criteria, screening recommendations, and biases from these studies. Results: Of the 537 identified studies, 8 met the inclusion criteria, encompassing 2536 children (mean age: 7 years). Five studies supported routine screening, while three opposed it. Studies varied significantly in their AAI definitions, using atlanto-dental interval (ADI) thresholds of 4 mm to 6 mm, the space available for cord (SAC), and the basion-axial interval (BAI). No study demonstrated a definitive correlation between radiological findings and neurological symptoms. Conclusions: Routine radiological screening for AAI in asymptomatic children with Trisomy 21 is not supported by consistent evidence. A selective screening approach, focusing on symptomatic patients or those engaging in high-risk activities, may be more appropriate. The standardization of radiological criteria and prospective studies are needed to refine screening recommendations. Full article

Background/Objectives: To screen a group of adolescents with Down Syndrome (Trisomy 21) for keratoconus and assess the feasibility of setting up a national screening service. Methods: Twenty-seven patients with Down Syndrome between 9 and 18 years of age attended our pilot keratoconus screening clinic. We recorded demographics, medical history, risk factors, best-corrected distance visual acuity, clinical examination results and corneal tomography results. The presence of keratoconus was confirmed by one of three corneal specialists based on clinical and tomographic findings. Tomographic analysis included zonal Kmax, thinnest point, inferior–superior asymmetry (IS Values), Belin/Ambrosio deviation value (BAD-D) and anterior and posterior elevation maps. Results: Early keratoconus was detected on tomography in 8 out of 54 eyes (15%) at the first review. These eyes were listed for crosslinking. The mean age of diagnosis was 14.6. Corneas in the Down Syndrome screening group were thinner and steeper (mean central corneal thickness (CCT) 479 µm vs. 536 µm and mean Kmax 49.2D vs. 45.8D, respectively) than healthy, age-matched controls from the literature. Conclusions: Fifteen percent of eyes (5 out of 27 patients) screened had tomographic evidence of keratoconus requiring treatment at their first review. We found an increased incidence of keratoconus in European individuals with Down Syndrome. Screening this vulnerable, high-risk population with corneal tomography can diagnose early keratoconus and enable corneal crosslinking to safely and effectively stabilise the disease. We advocate tomographic keratoconus screening for individuals with Down Syndrome in their mid-teens. Full article

Down syndrome (DS), the most common survivable autosomal aneuploidy, is associated with a high prevalence of congenital anomalies of the kidney and urinary tract (CAKUT), significantly increasing the risk of chronic kidney disease (CKD). This review examines the diversity of CAKUT phenotypes reported in individuals with DS, focusing on anomalies affecting the kidney, ureter, bladder, and urethra. According to available literature, hydronephrosis is the most common renal anomaly, often secondary to other CAKUT phenotypes, followed by renal hypoplasia and glomerulocystic disease. Furthermore, obstructive uropathies are also frequent but usually lack detailed characterization in the literature. Key features of CAKUT in DS, including reduced kidney size, renal cystic diseases, acquired glomerulopathies, reduced nephron number, and immature glomeruli heighten the risk of CKD. Also, early detection of lower urinary tract dysfunction (LUTD) is critical to prevent progressive upper urinary tract damage and CKD. Despite the prevalence of CAKUT in DS, reported between 0.22% and 21.16%, there is a lack of standardized diagnostic criteria, consistent terminology, and extended follow-up studies. Systematic screening from infancy, including regular renal monitoring via urinalysis and ultrasound, plays a critical role in the timely diagnosis and intervention of CAKUT. To further enhance diagnostic accuracy and develop effective therapeutic strategies, increased awareness and focused research into the genetic factors underlying these anomalies are essential. Moreover, a multidisciplinary approach is indispensable for managing CAKUT and its associated complications, ultimately ensuring better long-term outcomes and an improved quality of life for individuals with DS. Full article

KMT2A partial tandem duplication (PTD) involves intragenic KMT2A duplications and has been associated with poorer prognosis. In this study, we evaluated KMT2A PTD in 1277 patients with hematological malignancies using optical genome mapping (OGM). KMT2A PTD was detected in 35 patients with acute myeloid leukemia (AML) (7%), 5 patients with myelodysplastic syndrome (MDS) (2.2%), and 5 patients with chronic myelomonocytic leukemia (CMML) (7.1%). The PTDs varied in size, region, and copy number. An Archer RNA fusion assay confirmed KMT2A PTD in all 25 patients tested: 15 spanning exons 2 to 8 and 10 spanning exons 2 to 10. Most patients exhibited a normal (n = 21) or non-complex (n = 20) karyotype. The most common chromosomal abnormalities included loss of 20q or 7q and trisomy 11/gain of 11q. All patients had gene mutations, with FLT3 ITD and DNMT3A prevalent in AML and DNMT3A and RUNX1 common in MDS and CMML. Among patients who received treatment and had at least one follow-up bone marrow evaluation, 82% of those with de novo AML achieved complete remission after initial induction chemotherapy, whereas 90% of patients with secondary or refractory/relapsed AML showed refractory or partial responses. All but one patient with MDS and CMML were refractory to therapy. We conclude that OGM is an effective tool for detecting KMT2A PTD. Neoplasms with KMT2A PTD frequently harbor gene mutations and display normal or non-complex karyotypes. Patients with KMT2A PTD are generally refractory to conventional therapy, except for de novo AML. Full article

Down syndrome (DS) is a multisystemic disorder that includes accelerated aging caused by trisomy 21. In particular, overexpression of cystathionine-β-synthase (CBS) is linked to excess intracellular hydrogen sulfide (H₂S), a mitochondrial toxin at higher concentrations, which impairs cellular viability. Concurrent overexpression of superoxide dismutase 1 (SOD1) may increase oxidative stress by generating excess hydrogen peroxide (H₂O₂) while also mitigating the toxic H₂S burden via a non-canonical sulfide-oxidizing mechanism. We investigated the phenotypic variability in basal H₂S levels in relation to DS B lymphocyte cell health and SOD1 in H₂S detoxification. The H₂S levels were negatively correlated with the DS B lymphocyte growth rates but not with CBS protein. Pharmacological inhibition of SOD1 using LCS-1 significantly increased the H₂S levels to a greater extent in DS cells while also decreasing the polysulfide products of H₂S oxidation. However, DS cells exhibited elevated H₂O₂ and lipid peroxidation, representing potential toxic consequences of SOD1 overexpression. Treatment of DS cells with a pleiotropic carbon nanozyme (pleozymes) decreased the total oxidative stress and reduced the levels of the H₂S-generating enzymes CBS and 3-mercaptopyruvate sulfurtransferase (MPST). Our results indicate that pleozymes may bridge the protective and deleterious effects of DS SOD1 overexpression on H₂S metabolism and oxidative stress, respectively, with cytoprotective benefits. Full article

Down syndrome (DS) is a genetic disorder caused by an extra copy of chromosome 21 (trisomy 21 or T21) and is associated with an increased risk of early-onset Alzheimer’s disease (AD), also known as DS-associated AD (DSAD). Individuals with DS typically develop amyloid neuropathology in their late-thirties to early-forties and the mean age of onset of clinical dementia is approximately 55 years. Recent advances in AD clinical research have focused on monoclonal antibodies (mAbs) targeting amyloid-β (Aβ) plaques as a potential therapeutic approach. Therefore, there has been guarded enthusiasm about using anti-amyloid mAbs in the prevention/treatment of DSAD. This narrative review and perspective explores the current understanding of amyloid pathology in AD and DSAD, the rationale for using anti-amyloid mAbs in the treatment of DSAD, and the challenges and opportunities for research toward the application of this therapeutic strategy to older adults with DS. Full article

Background and Objectives: Down syndrome (DS) is the most common chromosomal disorder in the world. It is caused by the imbalance of the chromosomal constitution of 21 by free trisomy, translocation or mosaicism. Children and adolescents with Down syndrome have immune dysregulation and are more susceptible to infections. This study aims to evaluate hospitalizations of children and adolescents with DS in the pediatric ward of Botucatu Clinics Hospital (HCFMB) and to classify the population of children included in the study according to age, diagnosis, outpatient follow-up, length of stay and need for the intensive care unit (ICU). Thus, it will be possible to improve care for these children, aiming to reduce these hospitalizations. Materials and Methods: This study was an observational, cross-sectional study, with retrospective data collected from the last nine years of hospitalization, from January 2013 to December 2021, from children and adolescents with DS in the pediatric ward, emergency room, and the ICU of HCFMB. Children hospitalized in this period in the pediatric ward and ICU, in the age range of 30 days to 15 years, were included in this study. The evaluation of comorbidities that culminated in the need for hospitalization in this population can be the focus of actions to improve the diagnoses and conducts for this population, which can prevent worsening illness and hospitalizations in future populations. Results: In this analysis, 80 children with DS were evaluated, with a total of 283 hospitalizations. The most prevalent age group was 1 to 3 years, and the main cause was due to problems in the respiratory system (99 cases). Among the respiratory causes, the main cause of hospitalization was due to pneumonia in 50% of cases, followed by acute respiratory failure in 14%. The average hospitalization time was 8 days, and in 49 hospitalizations, the children required the ICU. The main cause of hospitalization in the ICU was due to respiratory causes (36%), followed by cardiac malformations (14%). During the ICU hospitalizations, there were 13 deaths, and we observed a higher prevalence of heart conditions and, in some cases, positive urine cultures in these children. Conclusions: The Hospital serves as a reference for pediatric hospitalizations within its region and beyond, owing to its specialized capabilities. The main causes of hospitalization were those related to the respiratory system and cardiac malformations. Roughly one-third of the children required admission to the intensive care unit. Full article

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. Full article

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. Full article

Down syndrome (DS) is caused by trisomy of chromosome 21 and is associated with characteristic features of appearance, intellectual impairment to varying degrees, organ defects, and health problems typical of this syndrome. Studies on the frequency of consumption of food products in this group show many irregularities, in particular too low consumption of vegetables and fruits, wholegrain cereal products and dairy products, and excessive consumption of meat products and sweets. It is necessary to correct eating habits. The diets of people with trisomy 21 should be consistent with the recommendations of rational nutrition for the general population and take into account specific dietary modifications related to the occurrence of diseases and health problems characteristic of this syndrome. Full article