في هذا الموضوع نعرض لكم أحدث دراسات السابقة أجنبية التي تناولت متلازمة داون Down Syndrome بالبحث والدراسة وفيما يلي عرض لتلك الدراسات بترتيب زمني.
1- Title: Prevalence of Obstructive Sleep Apnea in Children With Down Syndrome: A Meta-Analysis
To estimate the prevalence of obstructive sleep apnea (OSA) in children with Down syndrome. Two authors independently searched databases, namely PubMed, MEDLINE, EMBASE, and the Cochrane Review database. The keywords used were “Down syndrome,” “Trisomy 21,” “OSA,” “sleep apnea syndromes,” “polysomnography” and “polygraphy.”
The prevalence of OSA based on apnea-hypopnea index (AHI) greater than 1, 1.5, 2, 5, and 10 event/h was estimated using a random-effects model. Subgroup analyses were conducted for children in different countries, sample size, study year, and risk of bias. Finally, the prevalence of OSA was compared between two types of sleep studies (polysomnography versus polygraphy).
A total of 18 studies (1,200 children) were included (mean age: 7.7 years; 56% boys; mean sample size: 67 patients). Five studies had low risk of bias, and nine and four studies had moderate and high risk of bias, respectively. The OSA was evaluated through polygraphy in 2 studies, and polysomnography in 16 studies.
For children who underwent polysomnography, the prevalences of OSA based on AHI > 1, 1.5, 2, 5, and 10 events/h were 69%, 76%, 75%, 50%, and 34%, respectively. Subgroup analyses revealed no significant difference among all subgroups. Meta-regression showed that AHI > 5 events/h was inversely correlated with age (P < .001). Moreover, the prevalence of OSA based on AHI > 1.5 events/h was lower in polygraphy compared with polysomnography (59% versus 76%, P = .037).
OSA is highly prevalent in children with Down syndrome. Prevalence of moderate to severe OSA is higher in younger age.
2- Title: Mechanisms of Progression of Myeloid Preleukemia to Transformed Myeloid Leukemia in Children with Down Syndrome
Myeloid leukemia in Down syndrome (ML-DS) clonally evolves from transient abnormal myelopoiesis (TAM), a preleukemic condition in DS newborns. To define mechanisms of leukemic transformation, we combined exome and targeted resequencing of 111 TAM and 141 ML-DS samples with functional analyses. TAM requires trisomy 21 and truncating mutations in GATA1; additional TAM variants are usually not pathogenic. By contrast, in ML-DS, clonal and subclonal variants are functionally required.
We identified a recurrent and oncogenic hotspot gain-of-function mutation in myeloid cytokine receptor CSF2RB. By a multiplex CRISPR/Cas9 screen in an in vivo murine TAM model, we tested loss-of-function of 22 recurrently mutated ML-DS genes. Loss of 18 different genes produced leukemias that phenotypically, genetically, and transcriptionally mirrored ML-DS.
Labuhn, M., Perkins, K., Varghese, L., Garnett, C., Papaemmanuil, E., Metzner, M., … & Klusmann, J. H. (2019). Mechanisms of progression of myeloid preleukemia to transformed myeloid leukemia in children with Down syndrome. Cancer cell, 36(2), 123-138.
3 – Title: Down Syndrome and COVID-19: A Perfect Storm?
People with Down syndrome show signs of chronic immune dysregulation, including a higher prevalence of autoimmune disorders, increased rates of hospitalization during respiratory viral infections, and higher mortality rates from pneumonia and sepsis. At the molecular and cellular levels, they show markers of chronic autoinflammation, including interferon hyperactivity, elevated levels of many inflammatory cytokines and chemokines, and changes in diverse immune cell types reminiscent of inflammatory conditions observed in the general population.
However, the impact of this immune dysregulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and CoV disease of 2019 (COVID-19) remains unknown. This Perspective outlines why individuals with Down syndrome should be considered an at-risk population for severe COVID-19. Specifically, the immune dysregulation caused by trisomy 21 may result in an exacerbated cytokine release syndrome relative to that observed in the euploid population, thus justifying additional monitoring and specialized care for this vulnerable population.
4- Title: Medical vulnerability of individuals with Down syndrome to severe COVID-19–data from the Trisomy 21 Research Society and the UK ISARIC4C survey
Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS.
The mean age of COVID-19 patients with DS in the T21RS survey was 29 years (SD = 18). Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Joint/muscle pain and vomiting or nausea were less frequent (p < 0.01), whereas altered consciousness/confusion were more frequent (p < 0.01).
Risk factors for hospitalization and mortality were similar to the general population with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher in patients with DS (T21RS DS versus non-DS patients: risk ratio (RR) = 3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus non-DS patients: RR = 2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality.
Hüls, A., Costa, A. C., Dierssen, M., Baksh, R. A., Bargagna, S., Baumer, N. T., … & T21RS COVID-19 Initiative. (2021). Medical vulnerability of individuals with Down syndrome to severe COVID-19–data from the Trisomy 21 Research Society and the UK ISARIC4C survey. EClinicalMedicine, 33, 100769.
5- Title: Gross motor dysfunction and balance impairments in children and adolescents with Down syndrome: a systematic review
Individuals with Down syndrome present with several impairments such as hypotonia, ligament laxity, decreased muscle strength, insufficient muscular cocontraction, inadequate postural control, and disturbed proprioception. These factors are responsible for the developmental challenges faced by children with Down syndrome. These individuals also present with balance dysfunctions.
This systematic review aims to describe the motor dysfunction and balance impairments in children and adolescents with Down syndrome. We searched the Scopus, ScienceDirect, MEDLINE, Wiley, and EBSCO databases for observational studies evaluating the motor abilities and balance performance in individuals with Down syndrome. The review was registered on PROSPERO.
A total of 1,096 articles were retrieved; after careful screening and scrutinizing against the inclusion and exclusion criteria, 10 articles were included in the review. Overall, the children and adolescents with Down syndrome showed delays and dysfunction in performing various activities such as sitting, pulling to stand, standing, and walking. They also presented with compensatory mechanisms to maintain their equilibrium in static and dynamic activities.
Jain, P. D., Nayak, A., Karnad, S. D., & Doctor, K. N. (2022). Gross motor dysfunction and balance impairments in children and adolescents with Down syndrome: a systematic review. Clinical and Experimental Pediatrics, 65(3), 142.