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Revista Medica Del Instituto Mexicano... Sep 2023Down syndrome (DS) is the most common autosomal aneuploidy and the leading cause of intellectual disability of genetic origin worldwide. It is identified as a syndrome... (Review)
Review
Down syndrome (DS) is the most common autosomal aneuploidy and the leading cause of intellectual disability of genetic origin worldwide. It is identified as a syndrome in which the variability of its clinical manifestations and the severity of its phenotype have a multifactorial origin. Worldwide prevalence ranges between 1 per 700 live births and several factors that may be involved in the origin of DS have been proposed. Our objective was to describe updates regarding risk factors in the cytogenetic origin or cause of DS. We conducted a narrative review study in which a literature search was carried out from January to June 2022 in databases such as PubMed, EBSCO, Medigraphic, ClinicalKey, and meta-search engines such as Elsevier and Evidence Alerts. Only articles published in the last 10 years in English and Spanish were included. The search terms used were: Down syndrome, risk factors, prevention. Although DS is a very common chromosomal pathology worldwide, there is no single risk factor at the origin of meiotic or mitotic nondisjunction of chromosome 21, but rather each of the associated risk factors contributes to a greater or lesser degree to a cytogenetic predisposition in the etiology of trisomy 21. During the review it was identified that the main established risk factor associated with DS is still advanced maternal age (≥ 35 years).
Topics: Adult; Humans; Down Syndrome; Maternal Age; Nondisjunction, Genetic; Risk Factors; Female
PubMed: 37769135
DOI: 10.5281/zenodo.8316459 -
Journal of Clinical Immunology Aug 2020
Topics: Adaptive Immunity; Biomarkers; Comorbidity; Down Syndrome; History, 20th Century; Humans; Research
PubMed: 32712750
DOI: 10.1007/s10875-020-00837-z -
African Health Sciences Mar 2022regaining balance control is the key to decrease risk of falls in children with Down syndrome. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
regaining balance control is the key to decrease risk of falls in children with Down syndrome.
OBJECTIVES
To compare between the effect of mechanical vestibular stimulation and balance exercises on balance in children with Down syndrome.
METHODS
Thirty children participated in the study. They were divided randomly and equally into; group A and group B, both groups received the designed program with regular balance exercises for group A and mechanical vestibular stimulation for group B, treatment was conducted for one hour 3 times per week for 3 successive months. Balance as stability indexes (regarding anteroposterior, mediolateral and over all stability indexes) was evaluated before and after treatment by Biodex balance system.
RESULTS
T-test was conducted to compare the mean values of stability indexes between groups. Non-significant difference between groups was recorded before treatment (p value > 0.05), while improvement was recorded when comparing post and pretreatment results for both groups (p > 0.0001). More significant improvement was recorded for group B when comparing the post treatment results with group A (p > 0.05).
CONCLUSION
Mechanical vestibular stimulation is better added to the rehabilitation program to improve balance in children with Down syndrome.
Topics: Child; Down Syndrome; Exercise Therapy; Humans; Postural Balance
PubMed: 36032439
DOI: 10.4314/ahs.v22i1.46 -
Science Advances Jul 2023Lysosome dysfunction arises early and propels Alzheimer's disease (AD). Herein, we show that amyloid precursor protein (APP), linked to early-onset AD in Down syndrome...
Lysosome dysfunction arises early and propels Alzheimer's disease (AD). Herein, we show that amyloid precursor protein (APP), linked to early-onset AD in Down syndrome (DS), acts directly via its β-C-terminal fragment (βCTF) to disrupt lysosomal vacuolar (H)-adenosine triphosphatase (v-ATPase) and acidification. In human DS fibroblasts, the phosphorylated YENPTY internalization motif of APP-βCTF binds selectively within a pocket of the v-ATPase V0a1 subunit cytoplasmic domain and competitively inhibits association of the V1 subcomplex of v-ATPase, thereby reducing its activity. Lowering APP-βCTF Tyr phosphorylation restores v-ATPase and lysosome function in DS fibroblasts and in vivo in brains of DS model mice. Notably, lowering APP-βCTF Tyr phosphorylation below normal constitutive levels boosts v-ATPase assembly and activity, suggesting that v-ATPase may also be modulated tonically by phospho-APP-βCTF. Elevated APP-βCTF Tyr phosphorylation in two mouse AD models similarly disrupts v-ATPase function. These findings offer previously unknown insight into the pathogenic mechanism underlying faulty lysosomes in all forms of AD.
Topics: Mice; Humans; Animals; Amyloid beta-Protein Precursor; Down Syndrome; Alzheimer Disease; Adenosine Triphosphatases; Lysosomes; Disease Models, Animal; Amyloid beta-Peptides
PubMed: 37494443
DOI: 10.1126/sciadv.adg1925 -
Nefrologia 2022
Topics: Humans; Down Syndrome; Bone and Bones; Kidney
PubMed: 36396571
DOI: 10.1016/j.nefroe.2021.09.006 -
Neuron Dec 2020Microglia are brain-resident immune cells and regulate mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual...
Microglia are brain-resident immune cells and regulate mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by a supernumerary chromosome 21, containing also genes related to the immune system. In the hippocampus of the Dp(16) mouse model of DS and DS individuals, we found activated microglia, as assessed by their morphology; activation markers; and, for DS mice, electrophysiological profile. Accordingly, we found increased pro-inflammatory cytokine levels and altered interferon signaling in Dp(16) hippocampi. DS mice also showed decreased spine density and activity of hippocampal neurons and hippocampus-dependent cognitive behavioral deficits. Depletion of defective microglia or treatment with a commonly used anti-inflammatory drug rescued the neuronal spine and activity impairments and cognitive deficits in juvenile Dp(16) mice. Our results suggest an involvement of microglia in Dp(16)-mouse cognitive deficits and identify a new potential therapeutic approach for cognitive disabilities in DS individuals.
Topics: Adult; Age Factors; Aminopyridines; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cognition; Disease Models, Animal; Down Syndrome; Female; Hippocampus; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Pyrroles
PubMed: 33027640
DOI: 10.1016/j.neuron.2020.09.010 -
Cold Spring Harbor Perspectives in... Feb 2020Acute megakaryoblastic leukemia (AMKL) is a rare malignancy affecting megakaryocytes, platelet-producing cells that reside in the bone marrow. Children with Down... (Review)
Review
Acute megakaryoblastic leukemia (AMKL) is a rare malignancy affecting megakaryocytes, platelet-producing cells that reside in the bone marrow. Children with Down syndrome (DS) are particularly prone to developing the disease and have a different age of onset, distinct genetic mutations, and better prognosis as compared with individuals without DS who develop the disease. Here, we discuss the contributions of chromosome 21 genes and other genetic mutations to AMKL, the clinical features of the disease, and the differing features of DS- and non-DS-AMKL. Further studies elucidating the role of chromosome 21 genes in this disease may aid our understanding of how they function in other types of leukemia, in which they are frequently mutated or differentially expressed. Although researchers have made many insights into understanding AMKL, much more remains to be learned about its underlying molecular mechanisms.
Topics: Animals; Child; Down Syndrome; GATA1 Transcription Factor; Humans; Leukemia, Megakaryoblastic, Acute; Mutation
PubMed: 31548219
DOI: 10.1101/cshperspect.a034884 -
Italian Journal of Pediatrics Feb 2023Communicating the diagnosis of Down Syndrome to a couple of parents is never easy, whether before or after birth. As doctors, we must certainly rely on our own... (Review)
Review
Communicating the diagnosis of Down Syndrome to a couple of parents is never easy, whether before or after birth. As doctors, we must certainly rely on our own relational skills, but it is also necessary to be confident in some general indications, which are often overlooked in the strict hospital routine. This article is intended as a summary of the main articles published on this subject in the international literature, collecting and summarising the most important indications that have emerged in years of medical practice all over the world as well as in our personal experience. The diffusion of these guidelines is essential to help the doctor in this difficult task, on which there is often little training, and above all to guarantee to the parents the least traumatic communication possible.
Topics: Female; Pregnancy; Humans; Down Syndrome; Parents; Parturition; Communication
PubMed: 36759877
DOI: 10.1186/s13052-023-01419-6 -
Biomolecules Apr 2020Cystathionine-β-synthase (CBS), the first (and rate-limiting) enzyme in the transsulfuration pathway, is an important mammalian enzyme in health and disease. Its... (Review)
Review
Cystathionine-β-synthase (CBS), the first (and rate-limiting) enzyme in the transsulfuration pathway, is an important mammalian enzyme in health and disease. Its biochemical functions under physiological conditions include the metabolism of homocysteine (a cytotoxic molecule and cardiovascular risk factor) and the generation of hydrogen sulfide (HS), a gaseous biological mediator with multiple regulatory roles in the vascular, nervous, and immune system. CBS is up-regulated in several diseases, including Down syndrome and many forms of cancer; in these conditions, the preclinical data indicate that inhibition or inactivation of CBS exerts beneficial effects. This article overviews the current information on the expression, tissue distribution, physiological roles, and biochemistry of CBS, followed by a comprehensive overview of direct and indirect approaches to inhibit the enzyme. Among the small-molecule CBS inhibitors, the review highlights the specificity and selectivity problems related to many of the commonly used "CBS inhibitors" (e.g., aminooxyacetic acid) and provides a comprehensive review of their pharmacological actions under physiological conditions and in various disease models.
Topics: Animals; Cystathionine beta-Synthase; Down Syndrome; Enzyme Inhibitors; Humans; Hydrogen Sulfide; Neoplasms; Tacrolimus
PubMed: 32365821
DOI: 10.3390/biom10050697 -
Frontiers in Endocrinology 2023To analyze and determine the safety and efficacy of growth hormone (GH) treatment in Down syndrome (DS) pediatric patients and to weigh ethical aspects involved. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To analyze and determine the safety and efficacy of growth hormone (GH) treatment in Down syndrome (DS) pediatric patients and to weigh ethical aspects involved.
DESIGN
Systematic review and mini meta-analysis of the literature.
METHODS
A search was performed in PubMed, Embase, Scopus, and PsycINFO through August 2022. Eligible studies included those who answered at least one of the following two questions: 1) What is the effect of growth hormone treatment in children with Down syndrome? 2) What are the ethical arguments in favor and against growth hormone treatment for children with Down syndrome? Multiple reviewers independently screened each article for eligibility.
RESULTS
In total sixteen reports detailed medical effects of GH treatment in pediatric DS patients and eight studies dealt with ethical aspects of GH treatment. Treatment with GH resulted in significantly higher growth velocity in patients with DS. The ethical complexity is great but does not present insurmountable difficulties to the therapeutic option.
CONCLUSIONS
As GH treatment is safe and effective for short-term height growth, GH therapy should be considered in long-term treatment of DS children.
Topics: Humans; Child; Human Growth Hormone; Down Syndrome; Body Height; Insulin-Like Growth Factor I
PubMed: 37152958
DOI: 10.3389/fendo.2023.1135768