Correction to: Estimation of the number of people with Down syndrome in Europe.
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ABSTRACT:
SUBMITTER: de Graaf G
PROVIDER: S-EPMC9553865 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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Correction to: Estimation of the number of people with Down syndrome in Europe.
de Graaf Gert G Buckley Frank F Skotko Brian G BG
European journal of human genetics : EJHG 20221001 10
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Project description:We aimed to estimate the nonselective live birth prevalence, actual live birth prevalence, reduction percentage because of selective terminations, and population prevalence for Down syndrome (DS) in European countries. The number of people with DS alive in a country was estimated by first modeling the number of live births of children with DS by year of birth. Subsequently, for these different years of birth, survival curves for people with DS were constructed and then applied to these yearly estimates of live births with DS. For Europe, 2011-2015, we estimate 8,031 annual live births of children with DS, which would have been around 17,331 births annually, absent selective terminations. The estimated reduction of live birth prevalence was, on average, 54%, varying between 0% in Malta and 83% in Spain. As of 2015, we estimate 417,000 people with DS are living in Europe; without elective terminations, there would have been about 572,000 people with DS, which corresponds to a population reduction rate of 27%. Such statistics can be important barometers for prenatal testing trends and resource allocation within countries. Disability awareness initiatives and public policy initiatives can also be better grounded with these more precise estimates.
| S-EPMC7940428 | biostudies-literature
Project description:This study asks people with Down syndrome (DS), ages 12 and older, about their self-perception so that their information could be shared with new and expectant parents of children with DS. We analyzed valid and reliable survey instruments from 284 people with DS on the mailing lists of 6 non-profit DS organizations around the country. Among those surveyed, nearly 99% of people with DS indicated that they were happy with their lives, 97% liked who they are, and 96% liked how they look. Nearly 99% people with DS expressed love for their families, and 97% liked their brothers and sisters. While 86% of people with DS felt they could make friends easily, those with difficulties mostly had isolating living situations. A small percentage expressed sadness about their life. In our qualitative analysis, people with DS encouraged parents to love their babies with DS, mentioning that their own lives were good. They further encouraged healthcare professionals to value them, emphasizing that they share similar hopes and dreams as people without DS. Overall, the overwhelming majority of people with DS surveyed indicate they live happy and fulfilling lives.
| S-EPMC3740159 | biostudies-literature
Project description:Human trisomies can alter cellular phenotypes and produce congenital abnormalities such as Down syndrome (DS). Here we have generated induced pluripotent stem cells (iPSCs) from DS fibroblasts and introduced a TKNEO transgene into one copy of chromosome 21 by gene targeting. When selecting against TKNEO, spontaneous chromosome loss was the most common cause for survival, with a frequency of ~10(-4), while point mutations, epigenetic silencing, and TKNEO deletions occurred at lower frequencies in this unbiased comparison of inactivating mutations. Mitotic recombination events resulting in extended loss of heterozygosity were not observed in DS iPSCs. The derived, disomic cells proliferated faster and produced more endothelia in vivo than their otherwise isogenic trisomic counterparts, but in vitro hematopoietic differentiation was not consistently altered. Our study describes a targeted removal of a human trisomy, which could prove useful in both clinical and research applications.
| S-EPMC3705773 | biostudies-literature
Project description:Aneuploidy, an abnormal number of chromosomes, has previously been considered irremediable. Here, we report findings that euploid cells increased among cultured aneuploid cells after exposure to the protein ZSCAN4, encoded by a mammalian-specific gene that is ordinarily expressed in preimplantation embryos and occasionally in stem cells. For footprint-free delivery of ZSCAN4 to cells, we developed ZSCAN4 synthetic mRNAs and Sendai virus vectors that encode human ZSCAN4. Applying the ZSCAN4 biologics to established cultures of mouse embryonic stem cells, most of which had become aneuploid and polyploid, dramatically increased the number of euploid cells within a few days. We then tested the biologics on non-immortalized primary human fibroblast cells derived from four individuals with Down syndrome—the most frequent autosomal trisomy of chromosome 21. Within weeks after ZSCAN4 application to the cells in culture, fluorescent in situ hybridization with a chromosome 21-specific probe detected the emergence of up to 24% of cells with only two rather than three copies. High-resolution G-banded chromosomes further showed up to 40% of cells with a normal karyotype. These findings were confirmed by whole-exome sequencing. Similar results were obtained for cells with the trisomy 18 of Edwards syndrome. Thus a direct, efficient correction of aneuploidy in human fibroblast cells seems possible in vitro using human ZSCAN4.
| S-EPMC4596399 | biostudies-literature
Project description:BACKGROUND:Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). There is an understanding that an increase in L-glutamate contributes to the pathogenesis of cerebral ischemias and AD. Memantine acts as an antagonist of N-methyl-D-aspartate (NMDA) type receptors, which is thought to reduce abnormal activation of glutamate neurotransmission. It binds with a low affinity to the NMDA receptor and so should not prevent learning and the formation of memory. Memantine can improve cognitive function and slow the decline of AD in the general population over time, and is the subject of this review. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population. OBJECTIVES:To determine the effectiveness and safety of memantine for people with DS who develop AD. SEARCH STRATEGY:CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of memantine, as well as experts in the field, to ask about reports of unpublished or ongoing trials. SELECTION CRITERIA:Randomised controlled trials of participants with DS and AD in which treatment with memantine was administered compared with a placebo group. DATA COLLECTION AND ANALYSIS:No study was identified which met the inclusion criteria for this review. MAIN RESULTS:No study was identified which met inclusion criteria for this review, however there is an on-going randomised controlled study being conducted in the UK and data are expected in 2009. AUTHORS' CONCLUSIONS:As there are no included trials, recommendations cannot be made about memantine for AD in DS. Well-designed, adequately powered studies are required.
| S-EPMC7197456 | biostudies-literature
Project description:Cognitive impairment in Down syndrome (DS) has been linked to increased synaptic inhibition. The underlying mechanisms remain unknown, but memory deficits are rescued in DS mouse models by drugs targeting GABA receptors. Similarly, administration of epigallocatechin gallate (EGCG)-containing extracts rescues cognitive phenotypes in Ts65Dn mice, potentially through GABA pathway. Some developmental and cognitive alterations have been traced to increased expression of the serine-threonine kinase DYRK1A on Hsa21. To better understand excitation/inhibition balance in DS, we investigated the consequences of long-term (1-month) treatment with EGCG-containing extracts in adult mBACtgDyrk1a mice that overexpress Dyrk1a. Administration of POL60 rescued components of GABAergic and glutamatergic pathways in cortex and hippocampus but not cerebellum. An intermediate dose (60 mg/kg) of decaffeinated green tea extract (MGTE) acted on components of both GABAergic and glutamatergic pathways and rescued behavioral deficits as demonstrated on the alternating paradigm, but did not rescue protein level of GABA-synthesizing GAD67. These results indicate that excessive synaptic inhibition in people with DS may be attributable, in large part, to increased DYRK1A dosage. Thus, controlling the level of active DYRK1A is a clear issue for DS therapy. This study also defines a panel of synaptic markers for further characterization of DS treatments in murine models.
| S-EPMC4611057 | biostudies-literature
Project description:IntroductionDown syndrome, or trisomy 21, is the most diagnosed chromosomal abnormality and is associated with multiple orthopedic concerns, including scoliosis. We sought to examine the surgical treatment of scoliosis associated with Down syndrome with an emphasis on specific complications in this population.MethodsA retrospective review of 13 patients with Down syndrome who underwent surgical intervention for spinal deformity between 2000 and 2018 were identified. Postoperative complications were classified using the modified Clavien-Dindo-Sink system. Perioperative and final follow-up radiographic data were analyzed.ResultsThe mean age at surgery was 14.2 years (11-19) with a mean follow-up of 3.6 years (0.4-6.2) at the time of data collection. Seven (54%) patients had postoperative complications, all related to wound healing. Three patients (23%) had major complications (Clavien-Dindo-Sink grade ≥3). These included one deep surgical site infection, one hematoma, and one seroma, all requiring surgical drainage. Four additional patients (31%) had minor complications (Clavien-Dindo-Sink grade ≤2).DiscussionSurgical intervention for scoliosis in patients with Down syndrome is associated with high complication rates despite the use of more modern surgical techniques and implant types. Complications in this cohort primarily involved wound healing, whereas previous studies described high rates of postoperative implant failure, pseudoarthrosis, and significant curve progression, which were not experienced by the patients in this study. Although the etiology of wound-related complications is unknown, awareness of this risk may help surgeons optimize surgical technique, postoperative monitoring, and preoperative counseling of families.Level of evidenceIV-single-institution retrospective case series.
| S-EPMC11463090 | biostudies-literature
Project description:BackgroundImproved medical care over more than five decades has markedly increased life expectancy, from 12 years to approximately 60 years, in people with Down syndrome (DS). With increased survival into late adulthood, there is now a greater need for the medical care of people with DS to prevent and treat aging-related disorders. In the wider population, acquired cardiovascular diseases such as stroke and coronary heart disease are common with increasing age, but the risks of these diseases in people with DS are unknown. There are no population-level data on the incidence of acquired major cerebrovascular and coronary diseases in DS, and no data examining how cardiovascular comorbidities or risk factors in DS might impact on cardiovascular event incidence. Such data would be also valuable to inform health care planning for people with DS. Our objective was therefore to conduct a population-level matched cohort study to quantify the risk of incident major cardiovascular events in DS.Methods and findingsA population-level matched cohort study compared the risk of incident cardiovascular events between hospitalized patients with and without DS, adjusting for sex, and vascular risk factors. The sample was derived from hospitalization data within the Australian state of Victoria from 1993-2010. For each DS admission, 4 exact age-matched non-DS admissions were randomly selected from all hospitalizations within a week of the relevant DS admission to form the comparison cohort. There were 4,081 people with DS and 16,324 without DS, with a total of 212,539 person-years of observation. Compared to the group without DS, there was a higher prevalence in the DS group of congenital heart disease, cardiac arrhythmia, dementia, pulmonary hypertension, diabetes and sleep apnea, and a lower prevalence of ever-smoking. DS was associated with a greater risk of incident cerebrovascular events (Risk Ratio, RR 2.70, 95% CI 2.08, 3.53) especially among females (RR 3.31, 95% CI 2.21, 4.94) and patients aged ≤ 50 years old. The association of DS with ischemic strokes was substantially attenuated on adjustment for cardioembolic risk (RR 1.93, 95% CI 1.04, 3.20), but unaffected by adjustment for atherosclerotic risk. DS was associated with a 40-70% reduced risk of any coronary event in males (RR 0.58, 95% CI 0.40, 0.84) but not in females (RR 1.14, 95% CI 0.73, 1.77).ConclusionsDS is associated with a high risk of stroke, expressed across all ages. Ischemic stroke risk in DS appears mostly driven by cardioembolic risk. The greater risk of hemorrhagic stroke and lower risk of coronary events (in males) in DS remain unexplained.
| S-EPMC4589343 | biostudies-literature
Project description: Not available
| S-EPMC8763347 | biostudies-literature
Project description:Background: A prolonged electrocardiogram (ECG) QT interval is associated with cardiac events and increased mortality. Antipsychotics can prolong the QT interval. The QT interval requires correction (QTc) for heart rate using a formula or QT-nomogram. The QT and QTc can be calculated automatically by the ECG machine or manually; however, machine-measured QT(c) intervals may be inaccurate. Objective: We aimed to investigate the mean QTc and proportion of prolonged QTc intervals in people taking antipsychotic medicines. Methods: We conducted an observational retrospective chart review and data analysis of all consecutive patients taking antipsychotics, with an ECG record, admitted to the psychiatric unit of a large tertiary hospital in Brisbane, Australia, between 1 January 2017 and 30 January 2019. We investigated the mean QTc of people taking antipsychotics to determine differences using (a) machine versus manual QT interval measurement and (b) QTc correction formulae (Bazett, Fridericia, Framingham, Hodges and Rautaharju) and the QT-nomogram. We also determined the number of people with a prolonged QTc using different methods and compared rates of prolonged QTc with antipsychotic monotherapy and polypharmacy. Results: Of 920 included people, the mean (±SD) machine-measured, Bazett-corrected QT interval (recorded from the ECG) was 435 ms (±27), significantly longer (p < 0.001) than the mean manually measured corrected QT intervals with Fridericia 394 ms (±24), Framingham 395 ms (±22), Hodges 398 ms (±22) and Rautaharju 400 ms (±24) formulae. There were significantly more people with a prolonged QTc using machine-measured QT and the Bazett formula (12.0%, 110/920) when compared with manually measured QT and the Fridericia formula (2.2%, 20/920) or QT-nomogram (0.7%, 6/920). Rates of QTc prolongation did not differ between people taking antipsychotic polypharmacy compared with monotherapy. Conclusion: Machine-measured QTc using the Bazett formula overestimates the QTc interval length and number of people with a prolonged QTc, compared with other formulae and the QT-nomogram. We recommend manually measuring the QT and correcting with the Fridericia formula or QT-nomogram prior to modifying antipsychotic therapies.
| S-EPMC9210090 | biostudies-literature