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Aging - Envejecimiento

TÍTULO / TITLE:   - Neuropsychiatric Symptoms of Alzheimer´s Disease in Down Syndrome and Its Impact on Caregiver Distress.

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REVISTA / JOURNAL:    - J Alzheimers Dis. 2021 Mar 16. doi: 10.3233/JAD-201009.

Enlace a la Editora de la Revista http://dx.doi.org/10.3233/JAD-201009

AUTORES / AUTHORS: - Fonseca LM;et al.

INSTITUCIÓN / INSTITUTION: - Department of Medical Education and Clinical Science, Washington State University, Spokane, WA, USA. Programa Terceira Idade PROTER, Old Age Research Group, Department and Institute of Psychiatry, University of São Paulo School of Medicine 

RESUMEN / SUMMARY: - Neuropsychiatric symptoms (NPS) are non-cognitive manifestations common to dementia and other medical conditions, with important consequences for the patient, caregivers, and society. Studies investigating NPS in individuals with Down syndrome (DS) and dementia are scarce. OBJECTIVE: Characterize NPS and caregiver distress among adults with DS using the Neuropsychiatric Inventory (NPI). METHODS: We evaluated 92 individuals with DS (≥30 years of age), divided by clinical diagnosis: stable cognition, prodromal dementia, and AD. Diagnosis was determined by a psychiatrist using the Cambridge Examination for Mental Disorders of Older People with Downs Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). NPS and caregiver distress were evaluated by an independent psychiatrist using the NPI, and participants underwent a neuropsychological assessment with Cambridge Cognitive Examination (CAMCOG-DS). RESULTS: Symptom severity differed between-groups for delusion, agitation, apathy, aberrant motor behavior, nighttime behavior disturbance, and total NPI scores, with NPS total score being found to be a predictor of AD in comparison to stable cognition (OR for one-point increase in the NPI=1.342, p=0.012). Agitation, apathy, nighttime behavior disturbances, and total NPI were associated with CAMCOG-DS, and 62% of caregivers of individuals with AD reported severe distress related to NPS. Caregiver distress was most impacted by symptoms of apathy followed by nighttime behavior, appetite/eating abnormalities, anxiety, irritability, disinhibition, and depression (R2=0.627, F(15,76)=8.510, p<0.001). CONCLUSION: NPS are frequent and severe in individuals with DS and AD, contributing to caregiver distress. NPS in DS must be considered of critical relevance demanding management and treatment. Further studies are warranted to understand the biological underpinnings of such symptoms.

TÍTULO / TITLE:   - Normal levels of KIF5 but reduced KLC1 levels in both Alzheimer disease and Alzheimer disease in Down syndrome: evidence suggesting defects in anterograde transport.

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REVISTA / JOURNAL:    - Alzheimers Res Ther. 2021 Mar 10;13(1):59. doi: 10.1186/s13195-021-00796-6.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s13195-021-00796-6

AUTORES / AUTHORS: - Chen XQ;... Mobley WC

INSTITUCIÓN / INSTITUTION: - Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA.  

RESUMEN / SUMMARY: - BACKGROUND: Impaired axonal transport may contribute to the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD) and Down syndrome (DS). Axonal transport is a complex process in which specific motor proteins move cargoes to and from neuronal cell bodies and their processes. Inconsistent reports point to the changes in AD in the levels of the classical anterograde motor protein kinesin family member 5 (KIF5) and the primary neuronal KIF regulator kinesin light chain 1 (KLC1), raising the possibility that anterograde transport is compromised in AD. METHODS AND MATERIALS: To address inconsistencies and determine if the shared pathologies in AD and elderly DS subjects with dementia (AD in DS; AD-DS) extend to the changes in KIF5 and KLC1, we measured the levels of all the three KIF5 family members and KLC1 in the AD and AD-DS frontal cortex and AD temporal cortex and cerebellum in samples taken with a short postmortem interval. To support future studies to explore the cell biological basis for any changes detected, we also examined the levels of these proteins in the brains of young and aged adult mice in the Dp (16)1Yey/+ (Dp16) mouse model of DS and J20 mouse model of AD. RESULTS: There were no changes in comparison with controls in KIF5 family members in either the AD or AD-DS samples when normalized to either β-actin or glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Interestingly, however, samples from control brains as well as from AD and AD-DS demonstrated strong positive correlations between the levels of KIF5 family members, suggesting positive co-regulated expression. Importantly, while earlier reports pointed to a negative correlation between the levels of the amyloid precursor protein (APP) and KIF5A levels, we found the opposite to be true in AD-DS; this was especially striking given triplication of the APP gene, with increased APP protein levels. AD and control samples showed positive correlations between fl-hAPP and KIF5 membe

TÍTULO / TITLE:   - Common genetic signatures of Alzheimers disease in Down Syndrome.

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REVISTA / JOURNAL:    - F1000Res. 2020 Nov 5;9:1299. doi: 10.12688/f1000research.27096.1. eCollection 2020.

Enlace a la Editora de la Revista http://dx.doi.org/10.12688/f1000research.27096.1

AUTORES / AUTHORS: - Sharma A;et al.

INSTITUCIÓN / INSTITUTION: - BioScience Project, PO Box 352, Wakefield, MA, 01880, USA. 

RESUMEN / SUMMARY: - People with Down Syndrome (DS) are born with an extra copy of Chromosome (Chr) 21 and many of these individuals develop Alzheimer’s Disease (AD) when they age. This is due at least in part to the extra copy of the APP gene located on Chr 21. By 40 years, most people with DS have amyloid plaques which disrupt brain cell function and increase their risk for AD. About half of the people with DS develop AD and the associated dementia around 50 to 60 years of age, which is about the age at which the hereditary form of AD, early onset AD, manifests. In the absence of Chr 21 trisomy, duplication of APP alone is a cause of early onset Alzheimer’s disease, making it likely that having three copies of APP is important in the development of AD and in DS. In individuals with both DS and AD, early behavior and cognition-related symptoms may include a reduction in social behavior, decreased enthusiasm, diminished ability to pay attention, sadness, fearfulness or anxiety, irritability, uncooperativeness or aggression, seizures that begin in adulthood, and changes in coordination and walking. Methods: We investigate the relationship between AD and DS through integrative analysis of genesets derived from a MeSH query of AD and DS associated beta amyloid peptides, Chr 21, GWAS identified AD risk factor genes, and differentially expressed genes in DS individuals. Results: Unique and shared aspects of each geneset were evaluated based on functional enrichment analysis, transcription factor profile and network analyses. Genes that may be important to both disorders: ACSM1, APBA2, APLP1, BACE2, BCL2L, COL18A1, DYRK1A, IK, KLK6, METTL2B, MTOR, NFE2L2, NFKB1, PRSS1, QTRT1, RCAN1, RUNX1, SAP18 SOD1, SYNJ1, S100B. Conclusions: Our findings indicate that oxidative stress, apoptosis, and inflammation/immune system processes likely underlie the pathogenesis of AD and DS.

TÍTULO / TITLE:   - Down syndrome, increased risk of dementia and lipid disturbances.

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REVISTA / JOURNAL:    - J Mother Child. 2021 Jan 29;21(1):69-73. doi: 10.34763/devperiodmed.20172101.6973.

Enlace a la Editora de la Revista http://dx.doi.org/10.34763/devperiodmed.20172101.6973

AUTORES / AUTHORS: - Klosowska A;

INSTITUCIÓN / INSTITUTION: - J Mother Child. 2021 Jan 29;21(1):69-73. doi: 10.34763/devperiodmed.20172101.6973. 

RESUMEN / SUMMARY: - Down syndrome (DS) is the most common chromosomal aberration and genetically determined cause of intellectual disability. DS patients often present with some congenital defects and chronic diseases, including early onset dementia, which affects 70% of DS patients over 55 years of age and has a clinical presentation similar to Alzheimer disease (AD). The symptoms of DS originate from excessive genetic material within the “critical region” of the 21(st) chromosome. The “critical region” encompasses genes potentially associated with increase risk of dementia, e.g. the APP gene (amyloid beta precursor protein) which leads to excessive amyloid beta production. Post-mortem studies of DS patients brains revealed diffuse deposition of the insoluble form of amyloid beta (Aβ), which is a characteristic feature of AD. Moreover, those changes were commonly observed in subjects > 31 years old. The pathomechanisms of AD have not been fully elucidated and scientists are still searching for new risk factors that may contribute to the development of this common illness. Recent research proved that lipid disturbance, especially disorders in the metabolism of HDL (high density lipoprotein) may play a crucial role in this pathogenic process. There are many studies examining lipid and lipoprotein concentration in the DS population, but up to now there are insufficient studies comparing these parameters with memory impairment, which may be a useful model for better understanding of the dementia pathomechanism.

TÍTULO / TITLE:   - Increased choroidal thickness in adults with Down syndrome.

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REVISTA / JOURNAL:    - Alzheimers Dement (Amst). 2021 Mar 17;13(1):e12170. doi: 10.1002/dad2.12170. eCollection 2021.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/dad2.12170

AUTORES / AUTHORS: - Csincsik L;et al.

INSTITUCIÓN / INSTITUTION: - Wellcome-Wolfson Institute for Experimental Medicine Queens University Belfast Belfast UK.  

RESUMEN / SUMMARY: - INTRODUCTION: People with Down syndrome (DS) are particularly susceptible to Alzheimes disease (AD) due to the triplication of the amyloid precursor protein (APP) gene. In this cross-sectional study, we hypothesized that choroidal thinning reported in sporadic AD (sAD) is mirrored in adults with DS. METHODS: The posterior pole of the eye for 24 adults with DS and 16 age-matched controls (Ctrl) were imaged with optical coherence tomography. Choroidal thickness (ChT) was measured and analyzed in relation to cognitive status and cerebral amyloid beta (Aβ) load. RESULTS: ChT was increased in people with DS (pwDS) compared to Ctrl. This increase was associated with gender differences and positively correlated with cerebral Aβ load in a small subset. There was no significant correlation detected between ChT and age or cognitive status. DISCUSSION: In contrast to sAD this study found a significantly thicker choroid in pwDS. Whether these changes are related to Aβ pathology in DS needs further investigation.

TÍTULO / TITLE:   - Measuring cerebral perfusion with [(11)C]-PiB R1 in Down syndrome: associations with amyloid burden and longitudinal cognitive decline

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REVISTA / JOURNAL:    - Brain Commun. 2020 Nov 18;3(1):fcaa198. doi: 10.1093/braincomms/fcaa198. eCollection 2021.

Enlace a la Editora de la Revista http://dx.doi.org/10.1093/braincomms/fcaa198

AUTORES / AUTHORS: - Mak E et al.

INSTITUCIÓN / INSTITUTION: - Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, CB2 0QQ, UK. 

RESUMEN / SUMMARY: - Positron emission tomography imaging of glucose hypometabolism and amyloid deposition are two well-established methods to evaluate preclinical changes in Alzheimer’s disease and people with Down syndrome. However, the use of both imaging modalities may overburden participants, particularly those with intellectual disabilities and cognitive impairment. The relative tracer delivery of the [(11)C]-Pittsburgh Compound B has been proposed as a viable surrogate for cerebral perfusion. Here, we studied the impact of amyloid pathology on perfusion changes in Down syndrome and evaluated its associations with cognitive impairment. In total, 47 adults with Down syndrome underwent the [(11)C]-Pittsburgh Compound B imaging and structural imaging. The structural data were processed with Freesurfer to obtain anatomical segmentations and cortical thickness. The relative tracer delivery from [(11)C]-Pittsburgh Compound B was derived using a simplified reference tissue model. The sample was stratified into those with minimal amyloid burden (n=25) and those with elevated amyloid (n=22). We found significant and widespread reductions of cerebral perfusion in those with elevated amyloid burden, independent of age, gender, cognitive function and cortical thickness. In addition, cerebral perfusion was associated with the cognitive impairment among the Down syndrome group with elevated amyloid burden. These findings highlight the promising utility of the relative tracer delivery of the [(11)C]-Pittsburgh Compound B as a surrogate index in clinical trials for monitoring disease progression or tracking physiologic changes over time in Down syndrome.

TÍTULO / TITLE:   - Trisomy 21-induced dysregulation of microglial homeostasis in Alzheimer’s brains is mediated by USP25.

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REVISTA / JOURNAL:    - Sci Adv. 2021 Jan 1;7(1):eabe1340. doi: 10.1126/sciadv.abe1340. Print 2021 Jan.

Enlace a la Editora de la Revista http://dx.doi.org/10.1126/sciadv.abe1340

AUTORES / AUTHORS: - Zheng Q et al

INSTITUCIÓN / INSTITUTION: - Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian 361003, China. 

RESUMEN / SUMMARY: - Down syndrome (DS), caused by trisomy of chromosome 21, is the most significant risk factor for early-onset Alzheimers disease (AD); however, underlying mechanisms linking DS and AD remain unclear. Here, we show that triplication of homologous chromosome 21 genes aggravates neuroinflammation in combined murine DS-AD models. Overexpression of USP25, a deubiquitinating enzyme encoded by chromosome 21, results in microglial activation and induces synaptic and cognitive deficits, whereas genetic ablation of Usp25 reduces neuroinflammation and rescues synaptic and cognitive function in 5×FAD mice. Mechanistically, USP25 deficiency attenuates microglia-mediated proinflammatory cytokine overproduction and synapse elimination. Inhibition of USP25 reestablishes homeostatic microglial signatures and restores synaptic and cognitive function in 5×FAD mice. In summary, we demonstrate an unprecedented role for trisomy 21 and pathogenic effects associated with microgliosis as a result of the increased USP25 dosage, implicating USP25 as a therapeutic target for neuroinflammation in DS and AD.

TÍTULO / TITLE:   - Endosome Dysregulation in Down Syndrome: A Potential Contributor to Alzheimer Disease Pathology.

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REVISTA / JOURNAL:    - Ann Neurol. 2021 Feb 6. doi: 10.1002/ana.26042.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ana.26042

AUTORES / AUTHORS: - Filippone A;PraticD

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Intracellular protein trafficking via the endosomes plays a key role in the maintenance of normal neuronal function. Although many diseases of the central nervous system exhibit specific pathological hallmarks, abnormalities of the endosome system are common traits for several of them, including Alzheimer disease (AD). Three main routes originate from the endosomes: the recycling, degradation, and retrograde pathways. Studies have shown that the majority of Down syndrome subjects develop AD pathology and manifest altered morphology and number of endosomes, and abnormalities in lysosome acidification and exosome secretion, suggesting that dysfunction of one of these pathways could play a functional role in the AD-like phenotype of the syndrome. Two of the major endosomal routes are mediated by the retromer complex, a multimeric system responsible for transport of cargo from the endosome to the trans-Golgi network or to the cell membrane. Recently, a new endosome system structurally related to the retromer, called “retriever,” has been reported. Whereas we know a great deal about the neuropathophysiology of the retromer complex, no precise pathogenic role for the retriever has yet been identified. Here, we will review the neurobiology of the endosome system and its role as key player in the development of AD-like pathology in Down syndrome. Additionally, we will discuss current knowledge on these two main endosome systems, retromer and retriever, and their potential as novel therapeutic targets. ANN NEUROL 2021.

TÍTULO / TITLE:   - Alzheimers Disease in the Down Syndrome: An Overview of Genetics and Molecular Aspects.

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REVISTA / JOURNAL:    - Neurol India. 2021 Jan-Feb;69(1):32-41. doi: 10.4103/0028-3886.310062.

Enlace a la Editora de la Revista http://dx.doi.org/10.4103/0028-3886.310062

AUTORES / AUTHORS: - Gomes FC;et al.

INSTITUCIÓN / INSTITUTION: - Genetics and Molecular Biology Research Unit (UPGEM), Department of Molecular Biology, Sao José do Rio Preto Medical School (FAMERP), Sao José do Rio Preto - SP, Brazil. 

RESUMEN / SUMMARY: - The overexpression of the amyloid precursor protein (APP) gene, encoded on chromosome 21, has been associated in Down syndrome (DS) with the development of early-onset Alzheimer’s disease (EOAD). The increase in APP levels leads to an overproduction of amyloid-β (Aβ) peptide that accumulates in the brain. In response to this deposition, microglial cells are active and generate cascade events that include release cytokines and chemokine. The prolonged activation microglial cells induce neuronal loss, production of reactive oxygen species, neuron death, neuroinflammation, and consequently the development of Alzheimer’s disease (AD). The intrinsically deficient immune systems in people with DS result in abnormalities in cytokine levels, which possibly contribute to the development of neurodegenerative disorders such as AD. Knowledge about the biomarkers involved in the process of neurodegeneration and neuroinflamation is important for understanding the mechanisms involved in the incidence and the precocity of AD in individuals with DS.

Cardiology - Cardiología

TÍTULO / TITLE:   - Impact of prenatal screening on congenital heart defects in neonates with Down syndrome in the US.

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REVISTA / JOURNAL:    - Pediatr Res. 2021 Mar 5. doi: 10.1038/s41390-021-01416-7.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41390-021-01416-7

AUTORES / AUTHORS: - Hart SA; Nandi D; et al.

INSTITUCIÓN / INSTITUTION: - The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA. 

RESUMEN / SUMMARY: - Non-invasive prenatal screening (NIPS) has fundamentally changed the screening process for Down syndrome (DS). Rates of complex congenital heart defects (CHD) have decreased in international studies but whether these shifts exist in the US is unknown. METHODS: Encounters for neonates with DS from 2007 to 2018 were obtained from the Pediatric Health Information System database. CHD were categorized as complex CHD, atrioventricular septal defects (AVSD), ventricular septal defects (VSD), and tetralogy of Fallot (TOF). Comparisons were made between pre-NIPS era (2007-2010) vs. post-NIPS era (2014-2018) and between states with low vs. high access to pregnancy termination as described by the Guttmacher Institute. RESULTS: Among 9122 patients, 6% had complex CHD, 22% had an AVSD, 22% had a VSD, and 4% had TOF. No difference in proportions of CHD was seen between eras. A small difference was observed in the proportion of AVSD between states with low vs. high access to pregnancy termination (23 vs. 17%, p < 0.001). CONCLUSIONS: The proportion of CHD in patients with DS appears to be stable despite widespread adoption of NIPS in the US. Variations were observed between states with low vs. high access to pregnancy termination. Population based studies are needed to fully evaluate the current epidemiology of CHD in DS. IMPACT: Through investigation of the Pediatric Health Information System database, this study assesses contemporary epidemiology of congenital heart disease among patients with Down syndrome. It has been suggested that improved prenatal screening for Down syndrome has altered the cardiac phenotype in international populations. Whether a similar shift also exists in the United States is unknown. In a contemporary United States cohort, a shift in the proportion or type of heart defects over the past decade was not observed. Regional differences in the proportion of heart defects were seen and may be due to differential access to prenatal care.

TÍTULO / TITLE:   - Long-term trends in the prevalence of congenital heart defects in patients with down syndrome in southern Poland.

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REVISTA / JOURNAL:    - J Mother Child. 2021 Jan 29;23(3):184-189. doi: 10.34763/devperiodmed.20192303.184189.

Enlace a la Editora de la Revista http://dx.doi.org/10.34763/devperiodmed.20192303.184189

AUTORES / AUTHORS: - Dobosz A ; Bik-Multanowski M

INSTITUCIÓN / INSTITUTION: - Department of Medical Genetics, Jagiellonian University Medical College, Krakow, Poland. 

RESUMEN / SUMMARY: - Down syndrome is one of the most common chromosomal abnormalities in humans. Patients have typical dysmorphic features and various congenital malformations. Congenital heart defects were reported as the most common of the latter, occurring in approximately 50% of the cases. THE AIM: We aimed to analyse the long-term trends in the prevalence of Down syndrome and related heart defects in the population of southern Poland (Krakow region). MATERIAL AND METHODS: We analysed 500 consecutive patients with Down syndrome who were born from 2006 through 2017 and were diagnosed at the Department of Medical Genetics, Jagiellonian University. Next, we compared our results with the data obtained in previous regional studies. RESULTS: The prevalence of Down syndrome in the assessed period was 1.65 per 1,000 live births and was similar to the historical prevalence in our region. Cardiac malformations were detected in 57.6% of the patients and the common atrioventricular canal (CAVC) was the most frequent anomaly (35.1%). However, detailed analysis of the frequency of severe heart defects that usually require prompt surgical treatment in the course of infancy revealed that the percentage of CAVC has been significantly lower in recent years (p=0.033). CONCLUSIONS: The prevalence of Down syndrome and the overall frequency of congenital heart defects have not significantly changed in recent years. However, the frequency of CAVC has decreased, which could be related to the technical progress in prenatal detection of this severe anomaly, and to the subsequent elective terminations of affected pregnancies. Further population studies are required to confirm the presence of this trend and elucidate its background.

TÍTULO / TITLE:   - Congenital Heart Defect and Pulmonary Hypertension in Children With Down Syndrome: Clinical Profile Over Two Decades.

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REVISTA / JOURNAL:    - Cureus. 2021 Feb 7;13(2):e13212. doi: 10.7759/cureus.13212.

Enlace a la Editora de la Revista http://dx.doi.org/10.7759/cureus.13212

AUTORES / AUTHORS: - Alhuzaimi AN;et al

INSTITUCIÓN / INSTITUTION: - Pediatric Cardiology, Department of Cardiac Science, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, SAU. 

RESUMEN / SUMMARY: - To describe the frequency and spectrum of congenital heart defects (CHD) and pulmonary hypertension among pediatric patients with Down syndrome (DS) in Saudi Arabia. METHODS: A cross-sectional, retrospective study of the cardiac anomalies among pediatric patients (0-18 years) with DS had been seen and evaluated in one center from August 2001 to October 2020. The demographic data, the reason for referral, echocardiography data including presence and type of CHD, systolic function, atrioventricular regurgitation, and pulmonary hypertension (PHTN) were analyzed. RESULTS: Among the 468 pediatric patients with DS, 275 (58.8%) had one or more congenital heart defects (CHD). The most common types of CHD among DS pediatric patients were ventricular septal defect (29.45%), atrial septal defect (ASD) secundum (26.9%) and atrioventricular septal defect (AVSD) (22.9%), and moderate to large patent ductus arteriosus (PDA) (9.1%). Pulmonary hypertension analyzed in children older than two months of age and was present in 21.5% of patients with CHD and 2.2% of patients with no CHD. Multivariate logistic regression showed the presence of AVSD, large PDA, and ASD secundum which all independent predictors of pulmonary hypertension. CONCLUSION: Almost 60% of DS patients have CHD with pulmonary hypertension which affect almost one-fifth of patients with CHD. AVSD, hemodynamically significant PDA, and ASD secundum were the most common lesions associated with pulmonary hypertension.

Dental - Dental

TÍTULO / TITLE:   - Three-Dimensional Assessment of Craniofacial Features in Patients With Down Syndrome During the Mixed Dentition Period: A Case-Control Study. LINK: Link to its Abstract

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REVISTA / JOURNAL:    - Cleft Palate Craniofac J. 2021 Mar 9:1055665621998181. doi: 10.1177/1055665621998181.

Enlace a la Editora de la Revista http://dx.doi.org/10.1177/1055665621998181

AUTORES / AUTHORS: - Takizawa H ... Maki K;

INSTITUCIÓN / INSTITUTION: - Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan. 

RESUMEN / SUMMARY: - Down syndrome (DS) is a common congenital chromosomal disorder related to trisomy 21. Lateral cephalometric radiography studies have shown that patients with DS have characteristic craniofacial morphology; however, no 3-dimensional analysis studies have been performed to investigate the craniofacial features, including volumetric aspects, of patients with DS. The present study was performed to evaluate the craniofacial features, including volumetric aspects, of patients with DS and to compare these findings with control participants using cone beam computed tomography (CBCT). MATERIALS AND METHODS: The study sample consisted of 12 patients with DS and 12 control participants. All participants were examined by means of CBCT; the resulting images were used for evaluation of maxillary and mandibular volume, cranial base, and craniofacial measurements. Differences between patients with DS and control participants were statistically analyzed using Student t test. RESULTS: Compared to control participants, patients with DS exhibited statistically significant reductions in maxillary and mandibular volumes. Both sagittal and axial cranial base linear measurements were shorter in patients with DS than in control participants. In contrast, the cranial base angle was enhanced in patients with DS, compared with control participants. Moreover, condylion (Co)-gnathion, anterior nasal spine-menton, and Co-subspinale (point A) measurements were shorter in patients with DS than in control participants; the sella-nasion-mandibular plane angle was significantly reduced in patients with DS, compared with control participants. CONCLUSION: Our results suggest that patients with DS have distinct skeletal volume and craniofacial morphology features, relative to individuals without DS.

TÍTULO / TITLE:   - Masticatory function in children with Down syndrome.

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REVISTA / JOURNAL:    - Physiol Behav. 2021 Mar 16;235:113390. doi: 10.1016/j.physbeh.2021.113390.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.physbeh.2021.113390

AUTORES / AUTHORS: - Wintergerst A;Lpez-Morales MP

INSTITUCIÓN / INSTITUTION: - División de Estudios de Posgrado e Investigación, Facultad de Odontologí­a, Universidad Nacional Autónoma de México, Av. Universidad 3000, Col. Universidad Nacional Autónoma de México, CP 04510 Ciudad de México, México. 

RESUMEN / SUMMARY: - The objective was to study masticatory function of 8 to 10-year-old children with Down syndrome (DS) through the evaluation of maximum occlusal force and masticatory performance (via medium particle size) and compare it to that of children of the same age without DS. METHODS: A convenience sample of eight, 8-10-year-old children with DS were included in this cross-sectional study. The study had ethical approval and parents provided informed consent. Exclusion criteria were large carious lesions, dental pain or previous orthodontic/orthopedic treatment. Masticatory performance was evaluated with an artificial test food (Optosil Comfort) after 20 cycles and at swallowing threshold. The chewed material was collected, dried and sieved. The material on each sieve was weighed; the weights were used to calculate medium particle size. Maximum occlusal force (1st permanent molars) was determined using the GM10 Nagano Keiki Co.™ portable transducer. The number of cycles until swallowing threshold, cycle and sequence durations were also compared. The data for the reference group (n = 32) came from a previous study in children of the same age. Descriptive statistics as well as comparisons with Mann-Whitney tests and simple and multiple regression analysis were performed. Cutoff was set at p≤.05. RESULTS: Medium particle size is larger by 44% after 20 chewing cycles and 75% at swallowing threshold (p<.05) in children with DS. Median maximum occlusal force was 254 kN in DS children and 499 kN in children without the syndrome (p<.001). 48% of the variance in maximum occlusal force is explained by having DS. There were also significant differences in sequence and cycle durations. All significant differences had large effect sizes (˃1). Although the children with DS chewed more cycles before swallowing threshold the difference was not significant. CONCLUSIONS: Children with DS have approximately 50% of the masticatory performance and maximum occlusal force of children of the sa

Endocrinology/Nutrition - Endocrinología/Nutrición

TÍTULO / TITLE:   - Volumetric BMD by 3D-DXA and Trabecular Bone Score in Adults With Down Syndrome.

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REVISTA / JOURNAL:    - J Clin Densitom. 2021 Jan 30:S1094-6950(21)00011-1. doi: 10.1016/j.jocd.2021.01.010.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jocd.2021.01.010

AUTORES / AUTHORS: - Costa R;et al.

INSTITUCIÓN / INSTITUTION: - Adult Down Syndrome Outpatient Clinic, Department of Internal Medicine, Instituto de Investigación Sanitaria-Princesa (IIS-IP), Hospital Universitario de La Princesa, Madrid, España.  

RESUMEN / SUMMARY: - Adults with Down syndrome (DS) have lower bone mineral density (BMD) than the general population. The objective of our study was to describe bone mineral status in DS population through volumetric BMD (vBMD) and trabecular bone score (TBS). Retrospective study of 297 subjects recruited from the Adult DS Outpatient Clinic of a tertiary care hospital in Spain, who underwent a bone densitometry for clinical purposes between January 2010 and June 2015. vBMD determination and TBS analysis on conventional DXA (Hologic QDR 4500) densitometer were performed in this cohort. The mean (±SD) age of our population was 34.3 (±10.9) years; 51% were women. Trabecular vBMD at total hip and femoral neck was lower in males than in females (191.7 ± 48.4 mg/cm3 vs 206.9 ± 46.7 mg/cm3, p = 0.007, and 250.5 ± 70.1 mg/cm3 vs 275.7 ± 66.2 mg/cm3, p = 0.002, respectively). Trabecular and cortical vBMD decreased with age, but age decline in trabecular vBMD was more pronounced in males. Likewise, lumbar TBS declined with age being normal in 63%, low in 29% and very low in 8% of subjects with DS, without differences between sexes. TBS showed a positive correlation (r = 0.37; p < 0.001, Kappa index= 0.275) with conventional DXA lumbar Z-score. vBMD at the hip showed lower values in DS subjects than in the general population, especially in males. Moreover, TBS was also lower at lumbar spine. Therefore, both assessments could be used as complementary tools to areal BMD (Z-score) to assess bone status in DS subjects. 

TÍTULO / TITLE:   - Thyroid disorder in children and young people with Down syndrome: DSMIG guideline review.

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REVISTA / JOURNAL:    - Arch Dis Child Educ Pract Ed. 2021 Feb 8:edpract-2020-321080. doi: 10.1136/archdischild-2020-321080.

Enlace a la Editora de la Revista http://dx.doi.org/10.1136/archdischild-2020-321080

AUTORES / AUTHORS: - Dalrymple RA

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: -

Epidemiology - Epidemiología

TÍTULO / TITLE:   - Impact of prenatal screening on congenital heart defects in neonates with Down syndrome in the US.

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REVISTA / JOURNAL:    - Pediatr Res. 2021 Mar 5. doi: 10.1038/s41390-021-01416-7.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41390-021-01416-7

AUTORES / AUTHORS: - Hart SA; Nandi D; et al.

INSTITUCIÓN / INSTITUTION: - The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA. 

RESUMEN / SUMMARY: - BACKGROUND: Non-invasive prenatal screening (NIPS) has fundamentally changed the screening process for Down syndrome (DS). Rates of complex congenital heart defects (CHD) have decreased in international studies but whether these shifts exist in the US is unknown. METHODS: Encounters for neonates with DS from 2007 to 2018 were obtained from the Pediatric Health Information System database. CHD were categorized as complex CHD, atrioventricular septal defects (AVSD), ventricular septal defects (VSD), and tetralogy of Fallot (TOF). Comparisons were made between pre-NIPS era (2007-2010) vs. post-NIPS era (2014-2018) and between states with low vs. high access to pregnancy termination as described by the Guttmacher Institute. RESULTS: Among 9122 patients, 6% had complex CHD, 22% had an AVSD, 22% had a VSD, and 4% had TOF. No difference in proportions of CHD was seen between eras. A small difference was observed in the proportion of AVSD between states with low vs. high access to pregnancy termination (23 vs. 17%, p < 0.001). CONCLUSIONS: The proportion of CHD in patients with DS appears to be stable despite widespread adoption of NIPS in the US. Variations were observed between states with low vs. high access to pregnancy termination. Population based studies are needed to fully evaluate the current epidemiology of CHD in DS. IMPACT: Through investigation of the Pediatric Health Information System database, this study assesses contemporary epidemiology of congenital heart disease among patients with Down syndrome. It has been suggested that improved prenatal screening for Down syndrome has altered the cardiac phenotype in international populations. Whether a similar shift also exists in the United States is unknown. In a contemporary United States cohort, a shift in the proportion or type of heart defects over the past decade was not observed. Regional differences in the proportion of heart defects were seen and may be due to differential access to prenatal care.

Gastroenterology - Gastroenterología

TÍTULO / TITLE:   - Loss-of-function mutation of c-Ret causes cerebellar hypoplasia in mice with Hirschsprung disease and Down’s syndrome.

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REVISTA / JOURNAL:    - J Biol Chem. 2021 Feb 6;296:100389. doi: 10.1016/j.jbc.2021.100389.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jbc.2021.100389

AUTORES / AUTHORS: - Ohgami N;... Kato M;

INSTITUCIÓN / INSTITUTION: - Departments of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan; Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Science 

RESUMEN / SUMMARY: - The c-RET proto-oncogene encodes a receptor-tyrosine kinase. Loss-of-function mutations of RET have been shown to be associated with Hirschsprung disease and Down’s syndrome (HSCR-DS) in humans. DS is known to involve cerebellar hypoplasia, which is characterized by reduced cerebellar size. Despite the fact that c-Ret has been shown to be associated with HSCR-DS in humans and to be expressed in Purkinje cells (PCs) in experimental animals, there is limited information about the role of activity of c-Ret/c-RET kinase in cerebellar hypoplasia. We found that a loss-of-function mutation of c-Ret Y1062 in PCs causes cerebellar hypoplasia in c-Ret mutant mice. Wild-type mice had increased phosphorylation of c-Ret in PCs during postnatal development, while c-Ret mutant mice had postnatal hypoplasia of the cerebellum with immature neurite outgrowth in PCs and granule cells (GCs). c-Ret mutant mice also showed decreased numbers of glial fibers and mitogenic sonic hedgehog (Shh)-positive vesicles in the external germinal layer of PCs. c-Ret-mediated cerebellar hypoplasia was rescued by subcutaneous injection of a Smoothened agonist (SAG) as well as by reduced expression of Patched1, a negative regulator for Shh. Our results suggest that the loss-of-function mutation of c-Ret Y1062 results in the development of cerebellar hypoplasia via impairment of the Shh-mediated development of GCs and glial fibers in mice with HSCR-DS.

Genetics - Genética

TÍTULO / TITLE:   - Consequences of aneuploidy in human fibroblasts with trisomy 21.

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REVISTA / JOURNAL:    - Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):e2014723118. doi: 10.1073/pnas.2014723118.

Enlace a la Editora de la Revista http://dx.doi.org/10.1073/pnas.2014723118

AUTORES / AUTHORS: - Hwang S et al.

INSTITUCIÓN / INSTITUTION: - Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605. 

RESUMEN / SUMMARY: - An extra copy of chromosome 21 causes Down syndrome, the most common genetic disease in humans. The mechanisms contributing to aneuploidy-related pathologies in this syndrome, independent of the identity of the triplicated genes, are not well defined. To characterize aneuploidy-driven phenotypes in trisomy 21 cells, we performed global transcriptome, proteome, and phenotypic analyses of primary human fibroblasts from individuals with Patau (trisomy 13), Edwards (trisomy 18), or Down syndromes. On average, mRNA and protein levels were increased by 1.5-fold in all trisomies, with a subset of proteins enriched for subunits of macromolecular complexes showing signs of posttranscriptional regulation. These results support the lack of evidence for widespread dosage compensation or dysregulation of chromosomal domains in human autosomes. Furthermore, we show that several aneuploidy-associated phenotypes are present in trisomy 21 cells, including lower viability and increased dependency on serine-driven lipid synthesis. Our studies establish a critical role of aneuploidy, independent of triplicated gene identity, in driving cellular defects associated with trisomy 21.

TÍTULO / TITLE:   - Analyses stratified by maternal age and recombination further characterize genes associated with maternal nondisjunction of chromosome 21.

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REVISTA / JOURNAL:    - Prenat Diagn. 2021 Feb 17. doi: 10.1002/pd.5919.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/pd.5919

AUTORES / AUTHORS: - Chernus JM; Feingold E;

INSTITUCIÓN / INSTITUTION: - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA. 

RESUMEN / SUMMARY: - In our previous work, we performed the first genome-wide association study to find genetic risk factors for maternal nondisjunction of chromosome 21. The objective of the current work was to perform stratified analyses of the same dataset to further elucidate potential mechanisms of genetic risk factors. METHODS: We focused on loci that were statistically significantly associated with maternal nondisjunction based on this same dataset in our previous study and performed stratified association analyses in seven subgroups defined by age and meiotic recombination profile. In each analysis, we contrasted a different subgroup of mothers with the same set of fathers, the mothers serving as cases (phenotype: meiotic nondisjunction of chromosome 21) and the fathers as controls. RESULTS: Our stratified analyses identified several genes whose patterns of association are consistent with generalized effects across groups, as well as other genes that are consistent with specific effects in certain groups. CONCLUSIONS: While our results are epidemiological in nature and cannot conclusively prove mechanisms, we identified a number of patterns that are consistent with specific mechanisms. In many cases those mechanisms are strongly supported by available literature on the associated genes.

TÍTULO / TITLE:   - The etiology of Down syndrome: Maternal MCM9 polymorphisms increase risk of reduced recombination and nondisjunction of chromosome 21 during meiosis I within oocyte.

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REVISTA / JOURNAL:    - PLoS Genet. 2021 Mar 22;17(3):e1009462. doi: 10.1371/journal.pgen.1009462. eCollection 2021 Mar.

Enlace a la Editora de la Revista http://dx.doi.org/10.1371/journal.pgen.1009462

AUTORES / AUTHORS: - Pal U;et al.

INSTITUCIÓN / INSTITUTION: - Cytogenetics and Genomics Research Unit, Department of Zoology, University of Calcutta, Taraknath Palit Siksha Prangan (Ballygunge Science College Campus), Kolkata, West Bengal, India. 

RESUMEN / SUMMARY: - Altered patterns of recombination on 21q have long been associated with the nondisjunction chromosome 21 within oocytes and the increased risk of having a child with Down syndrome. Unfortunately the genetic etiology of these altered patterns of recombination have yet to be elucidated. We for the first time genotyped the gene MCM9, a candidate gene for recombination regulation and DNA repair in mothers with or without children with Down syndrome. In our approach, we identified the location of recombination on the maternal chromosome 21 using short tandem repeat markers, then stratified our population by the origin of meiotic error and age at conception. We observed that twenty-five out of forty-one single nucleotide polymorphic sites within MCM9 exhibited an association with meiosis I error (N = 700), but not with meiosis II error (N = 125). This association was maternal age-independent. Several variants exhibited aprotective association with MI error, some were neutral. Maternal age stratified characterization of cases revealed that MCM9 risk variants were associated with an increased chance of reduced recombination on 21q within oocytes. The spatial distribution of single observed recombination events revealed no significant change in the location of recombination among women harbouring MCM9 risk, protective, or neutral variant. Additionally, we identified a total of six novel polymorphic variants and two novel alleles that were either risk imparting or protective against meiosis I nondisjunction. In silico analyses using five different programs suggest the risk variants either cause a change in protein function or may alter the splicing pattern of transcripts and disrupt the proportion of different isoforms of MCM9 products within oocytes. These observations bring us a significant step closer to understanding the molecular basis of recombination errors in chromosome 21 nondisjunction within oocytes that leads to birth of child with Down syndrome.

TÍTULO / TITLE:   - Stable DNMT3L overexpression in SH-SY5Y neurons recreates a facet of the genome-wide Down syndrome DNA methylation signature.

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REVISTA / JOURNAL:    - Epigenetics Chromatin. 2021 Mar 9;14(1):13. doi: 10.1186/s13072-021-00387-7.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s13072-021-00387-7

AUTORES / AUTHORS: - Laufer BI;et al

INSTITUCIÓN / INSTITUTION: - Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA, 95616, USA 

RESUMEN / SUMMARY: - Down syndrome (DS) is characterized by a genome-wide profile of differential DNA methylation that is skewed towards hypermethylation in most tissues, including brain, and includes pan-tissue differential methylation. The molecular mechanisms involve the overexpression of genes related to DNA methylation on chromosome 21. Here, we stably overexpressed the chromosome 21 gene DNA methyltransferase 3L (DNMT3L) in the human SH-SY5Y neuroblastoma cell line and assayed DNA methylation at over 26 million CpGs by whole genome bisulfite sequencing (WGBS) at three different developmental phases (undifferentiated, differentiating, and differentiated). RESULTS: DNMT3L overexpression resulted in global CpG and CpG island hypermethylation as well as thousands of differentially methylated regions (DMRs). The DNMT3L DMRs were skewed towards hypermethylation and mapped to genes involved in neurodevelopment, cellular signaling, and gene regulation. Consensus DNMT3L DMRs showed that cell lines clustered by genotype and then differentiation phase, demonstrating sets of common genes affected across neuronal differentiation. The hypermethylated DNMT3L DMRs from all pairwise comparisons were enriched for regions of bivalent chromatin marked by H3K4me3 as well as differentially methylated sites from previous DS studies of diverse tissues. In contrast, the hypomethylated DNMT3L DMRs from all pairwise comparisons displayed a tissue-specific profile enriched for regions of heterochromatin marked by H3K9me3 during embryonic development. CONCLUSIONS: Taken together, these results support a mechanism whereby regions of bivalent chromatin that lose H3K4me3 during neuronal differentiation are targeted by excess DNMT3L and become hypermethylated. Overall, these findings demonstrate that DNMT3L overexpression during neurodevelopment recreates a facet of the genome-wide DS DNA methylation signature by targeting known genes and gene clusters that display pan-tissue differential methylation in DS.

TÍTULO / TITLE:   - Monozygotic twins discordant for homologous Robertsonian translocation trisomy 21 of 46, XX, +21, der (21;21) (q10; q10) in a twin-to-twin transfusion syndrome, case report.

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REVISTA / JOURNAL:    - BMC Pregnancy Childbirth. 2021 Jan 30;21(1):101. doi: 10.1186/s12884-021-03587-x.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s12884-021-03587-x

AUTORES / AUTHORS: - Cao D;et al

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Department of Fetal Medicine and Prenatal Diagnosis, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road,  

RESUMEN / SUMMARY: - Monozygotic twins are nearly identical in genotype and phenotype because monozygotic twins arise from one fertilized oocyte. In all cases of discordant karyotype in monozygotic twins, trisomy 21 accounts for about one in 385,000. Monozygotic twins discordant for Robertsonian translocation trisomy 21 of the der (21;21)(q10;q10), in which the additional chromosome originates from the father is rare. CASE PRESENTATION: A 28-year-old parous woman, G3P1A0, came to our institution for a dating scan at 8 weeks of gestation. The transvaginal ultrasound examination demonstrated a monochorionic diamniotic pregnancy. She and her husband were healthy, with no family history of trisomy 21 or other congenital diseases. The ultrasound examination of nuchal translucency thickness was discordant in twins at 13 weeks (twin A, NT 1.4 mm with CRL being 65 mm; twin B, NT 7.8 mm with CRL being 69 mm). At 17(+ 4) weeks, twin A was normal, but ventricular septal defect and the hypoplastic left heart was detected in twin B. The deepest vertical pocket was 18 mm in twin A (oligohydramnios) and 102 mm in Twin B (polyhydramnios). The bladder in twin A was absent. Ultrasound findings indicated TTTS Stage II. Amniocentesis was performed for the two fetuses. The karyotyping results revealed 46, XX in twin A but 46,XX,+ 21,der (21;21)(q10;q10) in twin B. For twin B, the parents opted for selective fetal termination by radiofrequency ablation. The procedure was uneventful. At 40(+ 5) weeks, twin A was born with a birth weight of 4120 g by vaginal delivery. CONCLUSIONS: The early detection of discordant karyotype and twin-to-twin transfusion syndrome is beneficial to the early intervention. In monozygotic twins with a discordant anomaly, the discordant karyotype should be considered.

Growth/Development - Crecimiento/Desarrollo

TÍTULO / TITLE:   - A landmark-free morphometrics pipeline for high-resolution phenotyping: application to a mouse model of Down syndrome.

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REVISTA / JOURNAL:    - Development. 2021 Mar 12;148(18):dev188631. doi: 10.1242/dev.188631.

Enlace a la Editora de la Revista http://dx.doi.org/10.1242/dev.188631

AUTORES / AUTHORS: - Toussaint N; Redhead Y;

INSTITUCIÓN / INSTITUTION: - Centre for Craniofacial Biology & Regeneration, King’s College London, UK.;The Francis Crick Institute, London NW1 1AT, UK. 

RESUMEN / SUMMARY: - Characterising phenotypes often requires quantification of anatomical shape. Quantitative shape comparison (morphometrics) traditionally uses manually located landmarks and is limited by landmark number and operator accuracy. Here, we apply a landmark-free method to characterise the craniofacial skeletal phenotype of the Dp1Tyb mouse model of Down syndrome and a population of the Diversity Outbred (DO) mouse model, comparing it with a landmark-based approach. We identified cranial dysmorphologies in Dp1Tyb mice, especially smaller size and brachycephaly (front-back shortening), homologous to the human phenotype. Shape variation in the DO mice was partly attributable to allometry (size-dependent shape variation) and sexual dimorphism. The landmark-free method performed as well as, or better than, the landmark-based method but was less labour-intensive, required less user training and, uniquely, enabled fine mapping of local differences as planar expansion or shrinkage. Its higher resolution pinpointed reductions in interior mid-snout structures and occipital bones in both the models that were not otherwise apparent. We propose that this landmark-free pipeline could make morphometrics widely accessible beyond its traditional niches in zoology and palaeontology, especially in characterising developmental mutant phenotypes.

TÍTULO / TITLE:   - Novel Insights from Fetal and Placental Phenotyping in Three Mouse Models of Down Syndrome.

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REVISTA / JOURNAL:    - Am J Obstet Gynecol. 2021 Mar 22:S0002-9378(21)00183-6. doi: 10.1016/j.ajog.2021.03.019.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ajog.2021.03.019

AUTORES / AUTHORS: - Adams AD;et al

INSTITUCIÓN / INSTITUTION: - Center for Precision Health Research ( Section on Prenatal Genomics and Fetal Therapy ), National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States of America. 

RESUMEN / SUMMARY: - In human fetuses with Down syndrome, placental pathology structural anomalies and growth restriction are present. There is currently a significant lack of information regarding the early lifespan in mouse models of Down syndrome. OBJECTIVE: The objective of this study was to examine embryonic (E18.5) and placental genotypes in the three most common mouse models of Down syndrome (Ts65Dn, Dp(16)1/Yey, Ts1Cje). Based on prenatal and placental phenotyping in three mouse models of Down syndrome we hypothesized that one or more of them would have a similar phenotype to human fetuses with trisomy 21, which would make it the most suitable for in utero treatment studies. STUDY DESIGN: C57BL6J/6 females were mated to Dp(16)/1Yey and Ts1Cje males and Ts65Dn females to C57BL/B6Eic3Sn.BLiAF1/J males. At E18.5, dams were euthanized. Embryos and placentas were examined blindly for weight and size. Embryos were characterized as euploid or trisomic, male or female by polymerase chain reaction. A subset (34 euploid, 34 trisomic) was examined for malformations. RESULTS: The Ts65Dn model showed the largest difference in fetal growth, brain development and placental development when comparing euploid and trisomic embryos. For the Dp16(1)/Yey model genotype did not impact fetal growth, but there were differences in brain and placental development. For the Ts1Cje model no significant association was found between genotype and fetal growth, brain development or placental development. Euploid embryos had no congenital anomalies; one was demised. Hepatic necrosis was seen in 6/12 (50%) of Dp(16)1/Yey and 1/12 (8%) Ts1Cje embryos; hepatic congestion/inflammation was observed in 3/10 (30%) Ts65Dn embryos. Renal pelvis dilation was seen in 5/12 (42%) Dp(16)1/Yey, 5/10 (50%) Ts65Dn and 3/12 (25%) Ts1Cje embryos. One Ts65Dn and one Dp(16)1/Yey embryo had an aortic outflow abnormality. Two Ts1Cje embryos had ventricular septal defects. Ts65Dn placentas had increased spongiotrophoblast necrosis CON

TÍTULO / TITLE:   - Differences in foot dimensions between children and adolescents with and without Down syndrome.

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REVISTA / JOURNAL:    - Disabil Rehabil. 2021 Mar 11:1-8. doi: 10.1080/09638288.2021.1895897.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/09638288.2021.1895897

AUTORES / AUTHORS: - Hassan NM et al

INSTITUCIÓN / INSTITUTION: - Discipline of Podiatry, School of Allied Health, Human Services and Sport, La Trobe University, Victoria, Australia. 

RESUMEN / SUMMARY: - Purpose: This study compared the differences in foot dimensions between children with and without Down syndrome using three-dimensional (3D) foot scans. Methods: 51 children with and 51 children without Down syndrome had a 3D scan taken of their right foot to compare the absolute and normalised (for height or foot length) measurements. Results: Normalised foot length was shorter in children with Down syndrome (MD -11.62 mm, 95% CI -15.06 to -8.18, p < 0.001). When normalised for foot length, ball of foot length (MD 2.87 mm, 95% CI 1.17 to 4.58, p = 0.001), diagonal and horizontal foot width (MD 3.65 mm, 95% CI 1.65 to 5.66, p < 0.001; MD 4.80 mm, 95% CI 2.88 to 6.72, p < 0.001, respectively), ball and instep girth (MD 10.60 mm, 95% CI 5.96 to 15.25, p < 0.001; MD 7.92 mm, 95% CI 3.02 to 12.82, p = 0.002, respectively) and fifth toe height (MD 3.14 mm, 95% CI 2.22 to 4.07, p < 0.001) were greater in children with Down syndrome. Conclusions: Children with Down syndrome have shorter, wider feet with greater girth and fifthtoe height measurements relative to children without Down syndrome. These findings have implications for footwear fit and the manufacturing of population-specific footwear.IMPLICATIONS FOR REHABILITATIONFootwear-fitting issues arise as a result of the unique foot shape of children with Down syndrome.There are substantial variations in the foot shape of children with and without Down syndrome.Children with Down syndrome require wider, deeper footwear at a given length to accommodate their foot dimensions.These findings have implications for the manufacturing of population-specific footwear.

TÍTULO / TITLE:   - Growth Patterns of Thai Children with Down Syndrome from Birth to 5 Years.

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REVISTA / JOURNAL:    - J Pediatr Genet. 2021 Mar;10(1):16-22. doi: 10.1055/s-0040-1713432. Epub 2020 Jun 30.

Enlace a la Editora de la Revista http://dx.doi.org/10.1055/s-0040-1713432

AUTORES / AUTHORS: - Boontan N; Rojnueangnit K

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Specific growth charts for children with Down syndrome (DS) have been developed in several countries, but not in Thailand. This pilot study aims to develop growth patterns for Thai children with DS, which will help clinicians to improve assessment and monitoring of the growth patterns for these children. A retrospective review of 80 children with DS who received care at Thammasat University Hospital between 2014 and 2018 was conducted. A total of 1,681 length/height and weight measurements were collected. Four sex-specific growth patterns of length/height and weight were generated with the fifth, 50th, and 95th percentile. The children with DS were lower in weight and shorter than general Thai children and children with DS in other countries. Therefore, each country should develop individual DS growth charts.

TÍTULO / TITLE:   - Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome.

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REVISTA / JOURNAL:    - Sci Rep. 2021 Feb 25;11(1):4715. doi: 10.1038/s41598-021-83757-1.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41598-021-83757-1

AUTORES / AUTHORS: - Starbuck JM;et al.... Martnez-Abadas N;

INSTITUCIÓN / INSTITUTION: - GREAB-Research Group in Biological Anthropology, Department of Evolutionary Biology, Ecology and Environmental Sciences (BEECA), Universitat de Barcelona (UB), Barcelona, España.  

RESUMEN / SUMMARY: - Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical s

TÍTULO / TITLE:   - Volumetric BMD by 3D-DXA and Trabecular Bone Score in Adults With Down Syndrome.

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REVISTA / JOURNAL:    - J Clin Densitom. 2021 Jan 30:S1094-6950(21)00011-1. doi: 10.1016/j.jocd.2021.01.010

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jocd.2021.01.010

AUTORES / AUTHORS: - Costa R;et al.

INSTITUCIÓN / INSTITUTION: - Adult Down Syndrome Outpatient Clinic, Department of Internal Medicine, Instituto de Investigación Sanitaria-Princesa (IIS-IP), Hospital Universitario de La Princesa, Madrid, España.  

RESUMEN / SUMMARY: - Adults with Down syndrome (DS) have lower bone mineral density (BMD) than the general population. The objective of our study was to describe bone mineral status in DS population through volumetric BMD (vBMD) and trabecular bone score (TBS). Retrospective study of 297 subjects recruited from the Adult DS Outpatient Clinic of a tertiary care hospital in Spain, who underwent a bone densitometry for clinical purposes between January 2010 and June 2015. vBMD determination and TBS analysis on conventional DXA (Hologic QDR 4500) densitometer were performed in this cohort. The mean (±SD) age of our population was 34.3 (±10.9) years; 51% were women. Trabecular vBMD at total hip and femoral neck was lower in males than in females (191.7 ± 48.4 mg/cm3 vs 206.9 ± 46.7 mg/cm3, p = 0.007, and 250.5 ± 70.1 mg/cm3 vs 275.7 ± 66.2 mg/cm3, p = 0.002, respectively). Trabecular and cortical vBMD decreased with age, but age decline in trabecular vBMD was more pronounced in males. Likewise, lumbar TBS declined with age being normal in 63%, low in 29% and very low in 8% of subjects with DS, without differences between sexes. TBS showed a positive correlation (r = 0.37; p < 0.001, Kappa index= 0.275) with conventional DXA lumbar Z-score. vBMD at the hip showed lower values in DS subjects than in the general population, especially in males. Moreover, TBS was also lower at lumbar spine. Therefore, both assessments could be used as complementary tools to areal BMD (Z-score) to assess bone status in DS subjects. 

Gynecology - Ginecología

TÍTULO / TITLE:   - Sexual behaviours and education in adolescents and young adults with Down syndrome: A grounded theory study of experiences and opinions of their mothers in Turkey.

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REVISTA / JOURNAL:    - :Res Dev Disabil. 2021 May;112:103907. doi: 10.1016/j.ridd.2021.103907. Epub 2021 Feb 26.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ridd.2021.103907

AUTORES / AUTHORS: - Gokgoz C;... Kabukcuoglu K;

INSTITUCIÓN / INSTITUTION: - Akdeniz University, Faculty of Nursing, Department of Obstetrics & Gynaecological Nursing, Antalya, Turkey.  

RESUMEN / SUMMARY: - This study aimed to gain a deeper understanding of the experiences and opinions of mothers about sexual behaviours and sexual education of their children with DS who are AYAs in Turkey. The study utilised a classic grounded theory approach. In-depth interviews were conducted with 12 mothers. Data were analyzed by the constant comparative method. Mothers expressed that they could not address the sexual needs of their child because they did not feel they could provide sufficient care to their child. Mothers used pressure and control tactics and neglect of the sexuality to cope with their children’s sexuality. Mothers described their meaning of the sexuality, fear of stigmatization and gender issues as determinant factors on the dealing with the sexuality. They stated their knowledge about sexuality is not enough to provide sexual education. Many cultural issues such as gender, meaning of the sexuality and burden of care was described as determinant factors and difficulties to providing sexual education. Therefore, educational and supportive programmes for parents should be conducted. Comprehensive, valid and individualized sexual education program also should be provided AYAs with DS.

TÍTULO / TITLE:   - Association between Down Syndrome and Disorders of Sex Development: Report of Three Cases and Review of 188 Cases in the Literature.

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REVISTA / JOURNAL:    - Sex Dev. 2021 Mar 2:1-9. doi: 10.1159/000513415.

Enlace a la Editora de la Revista http://dx.doi.org/10.1159/000513415

AUTORES / AUTHORS: - Santos-Neto OO;... Guerra-Junior G;

INSTITUCIÓN / INSTITUTION: - Interdisciplinary Group for the Study of Gender Determination and Differentiation (GIEDDS), School of Medical Sciences (FCM), State University of Campinas (UNICAMP), Campinas, Brazil,  

RESUMEN / SUMMARY: - In this study, we present 3 cases of Down syndrome (DS) associated with disorders/differences of sex development (DSD) and review the literature on this topic. Case 1: 1-year-old child with male genitalia and DS phenotype, 47,XX,+21 karyotype and testicular DSD. Case 2: 11-month-old child with male genitalia and few DS dysmorphisms, 45,X/47,XY,+21 karyotype, and mixed gonadal dysgenesis. Case 3: 4-month-old child with female genitalia and DS phenotype, 47,XY,+21 karyotype and XY complete gonadal dysgenesis. In the literature, among 188 patients, 107 (57%) had Klinefelter syndrome and 61 (33%) Turner syndrome, 12 (6%) had mixed gonadal dysgenesis, 2 (1%) had partial androgen insensitivity, 2 (1%) ovotesticular DSD, and the others had congenital adrenal hyperplasia, XY partial gonadal dysgenesis, XY complete gonadal dysgenesis, and complete androgen insensitivity (1 case each). A typical DS phenotype was found in all individuals of the revision, with the exception of one case, but DSD features were not always reported. In conclusion, the association of DS with sex chromosome DSD is the most frequently observed, whereas associations with 46,XX and 46,XY DSD is extremely rare.

Hematology/Oncology - Hematología/Oncología

TÍTULO / TITLE:   - The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis.

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REVISTA / JOURNAL:    - Nat Commun. 2021 Feb 5;12(1):821. doi: 10.1038/s41467-021-21064-z.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41467-021-21064-z

AUTORES / AUTHORS: - Muskens IS;et al.

INSTITUCIÓN / INSTITUTION: - Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, U 

RESUMEN / SUMMARY: - Down syndrome is associated with genome-wide perturbation of gene expression, which may be mediated by epigenetic changes. We perform an epigenome-wide association study on neonatal bloodspots comparing 196 newborns with Down syndrome and 439 newborns without Down syndrome, adjusting for cell-type heterogeneity, which identifies 652 epigenome-wide significant CpGs (P<7.67—10(-8)) and 1,052 differentially methylated regions. Differential methylation at promoter/enhancer regions correlates with gene expression changes in Down syndrome versus non-Down syndrome fetal liver hematopoietic stem/progenitor cells (P<0.0001). The top two differentially methylated regions overlap RUNX1 and FLI1, both important regulators of megakaryopoiesis and hematopoietic development, with significant hypermethylation at promoter regions of these two genes. Excluding Down syndrome newborns harboring preleukemic GATA1 mutations (N=30), identified by targeted sequencing, has minimal impact on the epigenome-wide association study results. Down syndrome has profound, genome-wide effects on DNA methylation in hematopoietic cells in early life, which may contribute to the high frequency of hematological problems, including leukemia, in children with Down syndrome.

TÍTULO / TITLE:   - : Predictive factors for the development of leukemia in patients with transient abnormal myelopoiesis and Down syndrome.

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REVISTA / JOURNAL:    - Leukemia. 2021 Mar 3. doi: 10.1038/s41375-021-01171-y.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41375-021-01171-y

AUTORES / AUTHORS: - Yamato G;et al.

INSTITUCIÓN / INSTITUTION: - Department of Hematology/Oncology, Gunma Children’s Medical Center, Gunma, Japan.; Department of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan. 

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - Leukemia Risk in a Cohort of 3.9 Million Children with and without Down Syndrome.

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REVISTA / JOURNAL:    - J Pediatr. 2021 Mar 6:S0022-3476(21)00212-2. doi: 10.1016/j.jpeds.2021.03.001.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jpeds.2021.03.001

AUTORES / AUTHORS: - Marlow EC;... Miglioretti DL;

INSTITUCIÓN / INSTITUTION: - Department of Public Health Sciences, University of California, Davis, Davis, CA; Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Salt Lake City, UT.  

RESUMEN / SUMMARY: - To assess leukemia risks among children with Down syndrome in a large, contemporary cohort. Study design: Retrospective cohort study including 3 905 399 children born 1996-2016 in 7 US healthcare systems or Ontario, Canada, and followed from birth to cancer diagnosis, death, age 15 years, disenrollment, or December 30, 2016. Down syndrome was identified using International Classification of Diseases, Ninth and Tenth Revisions, diagnosis codes. Cancer diagnoses were identified through linkages to tumor registries. Incidence and hazard ratios (HRs) of leukemia were estimated for children with Down syndrome and other children adjusting for health system, childs age at diagnosis, birth year, and sex. Results: Leukemia was diagnosed in 124 of 4401 children with Down syndrome and 1941 of 3 900 998 other children. In children with Down syndrome, the cumulative incidence of acute myeloid leukemia (AML) was 1405/100 000 (95% CI 1076-1806) at age 4 years and unchanged at age 14 years. The cumulative incidence of acute lymphoid leukemia in children with Down syndrome was 1059/100 000 (95% CI 755-1451) at age 4 and 1714/100 000 (95% CI 1264-2276) at age 14 years. Children with Down syndrome had a greater risk of AML before age 5 years than other children (HR 399, 95% CI 281-566). Largest HRs were for megakaryoblastic leukemia before age 5 years (HR 1500, 95% CI 555-4070). Children with Down syndrome had a greater risk of acute lymphoid leukemia than other children regardless of age (<5 years: HR 28, 95% CI 20-40, ≥5 years HR 21, 95% CI 12-38). Conclusions: Down syndrome remains a strong risk factor for childhood leukemia, and associations with AML are stronger than previously reported.

TÍTULO / TITLE:   - Post-induction MRD by FCM and GATA1-PCR are significant prognostic factors for myeloid leukemia of Down syndrome.

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REVISTA / JOURNAL:    - Leukemia. 2021 Feb 15. doi: 10.1038/s41375-021-01157-w.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41375-021-01157-w

AUTORES / AUTHORS: - Taga T, Tanaka S;et al.

INSTITUCIÓN / INSTITUTION: - Department of Clinical Biostatistics, Graduate School of Medicine Kyoto University, Kyoto, Japan. 

RESUMEN / SUMMARY: - Myeloid leukemia of Down syndrome (ML-DS) is associated with good response to chemotherapy, resulting in favorable outcomes. However, no universal prognostic factors have been identified to date. To clarify a subgroup with high risk of relapse, the role of minimal residual disease (MRD) was explored in the AML-D11 trial by the Japanese Pediatric Leukemia/Lymphoma Study Group. MRD was prospectively evaluated at after induction therapy and at the end of all chemotherapy, using flow cytometry (FCM-MRD) and GATA1-targeted deep sequencing (GATA1-MRD). A total of 78 patients were eligible and 76 patients were stratified to the standard risk (SR) group by morphology. In SR patients, FCM-MRD and GATA1-MRD after induction were positive in 5/65 and 7/59 patients, respectively. Three-year event-free survival (EFS) and overall survival (OS) rates were 93.3% and 95.0% in the FCM-MRD-negative population, and 60.0% and 80.0% in the positive population. Three-year EFS and OS rates were both 96.2% in the GATA1-MRD-negative population, and 57.1% and 71.4% in the positive population. Adjusted hazard ratios for associations of FCM-MRD or GATA1-MRD with EFS were 10.98 (p = 0.01) and 27.68 (p < 0.01), respectively. Detection of MRD by either FCM or GATA1 after initial induction therapy represents a significant prognostic factor for predicting ML-DS relapse.

TÍTULO / TITLE:   - Down syndrome with neonatal alloimmune thrombocytopenia due to anti-HLA A31 and B61 antibodies.

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REVISTA / JOURNAL:    - Int J Hematol. 2021 Feb 11. doi: 10.1007/s12185-021-03092-z.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s12185-021-03092-z

AUTORES / AUTHORS: - Shima E;et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan. 

RESUMEN / SUMMARY: - Neonatal alloimmune thrombocytopenia (NAIT) arises from fetomaternal platelet incompatibility that results in transplacental passage of maternal antibodies mostly against fetal human platelet antigens (HPA), whereas NAIT due to anti-human leukocyte antigen (HLA) antibodies is extremely rare. Here, we report a case of Down syndrome (DS) with NAIT that was attributed to HLA antibodies. A boy with DS was delivered at 36 weeks’ gestation. His platelet count declined to 13.0 × 10(9)/L, suggestive of NAIT rather than other conditions, including transient abnormal myelopoiesis. Random platelet concentrates and intravenous immunoglobulin administration resolved the thrombocytopenia without clinical complications. Immunoserological investigations detected anti-HLA, but no anti-HPA antibodies in samples from the patient and the mother. HLA typing and cross-matching indicated that anti-HLA antibodies to paternal HLA A31 and B61, which had probably been induced during a prior pregnancy, led to NAIT in this case. Although it is a rare condition, healthcare providers should consider NAIT due to HLA antibodies and be vigilant for subsequent cases in DS.

TÍTULO / TITLE:   - Pluripotent stem cell model of early hematopoiesis in Down syndrome reveals quantitative effects of short-form GATA1 protein on lineage specification

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REVISTA / JOURNAL:    - PLoS One. 2021 Mar 29;16(3):e0247595. doi: 10.1371/journal.pone.0247595. eCollection 2021.

Enlace a la Editora de la Revista http://dx.doi.org/10.1371/journal.pone.0247595

AUTORES / AUTHORS: - Matsuo S;et al.

INSTITUCIÓN / INSTITUTION: - Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan. 

RESUMEN / SUMMARY: - Children with Down syndrome (DS) are susceptible to two blood disorders, transient abnormal myelopoiesis (TAM) and Down syndrome-associated acute megakaryocytic leukemia (DS-AMKL). Mutations in GATA binding protein 1 (GATA1) have been identified as the cause of these diseases, and the expression levels of the resulting protein, short-form GATA1 (GATA1s), are known to correlate with the severity of TAM. On the other hand, despite the presence of GATA1 mutations in almost all cases of DS-AMKL, the incidence of DS-AMKL in TAM patients is inversely correlated with the expression of GATA1s. This discovery has required the need to clarify the role of GATA1s in generating the cells of origin linked to the risk of both diseases. Focusing on this point, we examined the characteristics of GATA1 mutant trisomy-21 pluripotent stem cells transfected with a doxycycline (Dox)-inducible GATA1s expression cassette in a stepwise hematopoietic differentiation protocol. We found that higher GATA1s expression significantly reduced commitment into the megakaryocytic lineage at the early hematopoietic progenitor cell (HPC) stage, but once committed, the effect was reversed in progenitor cells and acted to maintain the progenitors. These differentiation stage-dependent reversal effects were in contrast to the results of myeloid lineage, where GATA1s simply sustained and increased the number of immature myeloid cells. These results suggest that although GATA1 mutant cells cause the increase in myeloid and megakaryocytic progenitors regardless of the intensity of GATA1s expression, the pathways vary with the expression level. This study provides experimental support for the paradoxical clinical features of GATA1 mutations in the two diseases.

TÍTULO / TITLE:   - Molecular Mechanisms of the Genetic Predisposition to Acute Megakaryoblastic Leukemia in Infants With Down Syndrome.

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REVISTA / JOURNAL:    - Front Oncol. 2021 Mar 11;11:636633. doi: 10.3389/fonc.2021.636633. eCollection 2021

Enlace a la Editora de la Revista http://dx.doi.org/10.3389/fonc.2021.636633

AUTORES / AUTHORS: - Grimm J;et al.

INSTITUCIÓN / INSTITUTION: - Pediatric Hematology and Oncology, Martin Luther University Halle-Wittenberg, Halle, Germany.Department of Internal Medicine IV, Oncology/Hematology, Martin Luther University Halle-Wittenberg, Halle, Germany. 

RESUMEN / SUMMARY: - Individuals with Down syndrome are genetically predisposed to developing acute megakaryoblastic leukemia. This myeloid leukemia associated with Down syndrome (ML-DS) demonstrates a model of step-wise leukemogenesis with perturbed hematopoiesis already presenting in utero, facilitating the acquisition of additional driver mutations such as truncating GATA1 variants, which are pathognomonic to the disease. Consequently, the affected individuals suffer from a transient abnormal myelopoiesis (TAM)-a pre-leukemic state preceding the progression to ML-DS. In our review, we focus on the molecular mechanisms of the different steps of clonal evolution in Down syndrome leukemogenesis, and aim to provide a comprehensive view on the complex interplay between gene dosage imbalances, GATA1 mutations and somatic mutations affecting JAK-STAT signaling, the cohesin complex and epigenetic regulators.

Infectious diseases - Infecciones

TÍTULO / TITLE:   - Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome.

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REVISTA / JOURNAL:    - Genes (Basel). 2021 Feb 13;12(2):268. doi: 10.3390/genes12020268.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/genes12020268

AUTORES / AUTHORS: - Ferrari M; Stagi S

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Within immune system-related diseases, autoimmunity has always represented a field of great interest, although many aspects remain poorly understood even today. Genetic syndromes associated with immunity disorders are common and represent an interesting model for a better understanding of the underlying mechanism of autoimmunity predisposition. Among these conditions, Down syndrome (DS) certainly deserves special attention as it represents the most common genetic syndrome associated with immune dysregulation, involving both innate and adaptive immunity. Autoimmunity represents a well-known complication of DS: it is estimated that people affected by this disease present a risk four to six times higher than the normal population to develop autoimmune diseases such as celiac disease, type 1 diabetes mellitus, and hypo- or hyperthyroidism. Several factors have been considered as possible etiology, including genetic and epigenetic modifications and immune dysregulation. In times in which the life expectancy of people with DS has been extremely prolonged, thanks to improvements in the diagnosis and treatment of congenital heart disease and infectious complications, knowledge of the mechanisms and proper management of autoimmune diseases within this syndrome has become essential. In this short review, we aim to report the current literature regarding the genetic, immune, and environmental factors that have been proposed as the possible underlying mechanism of autoimmunity in individuals with DS, with the intent to provide insight for a comprehensive understanding of these diseases in genetic syndromes.

TÍTULO / TITLE:   - Medical vulnerability of individuals with Down syndrome to severe COVID-19-data from the Trisomy 21 Research Society and the UK ISARIC4C survey.

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REVISTA / JOURNAL:    - EClinicalMedicine. 2021 Mar;33:100769. doi: 10.1016/j.eclinm.2021.100769. Epub 2021 Feb 22.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.eclinm.2021.100769

AUTORES / AUTHORS: - Hls A;... Strydom A

INSTITUCIÓN / INSTITUTION: - Department of Epidemiology and Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA. 

RESUMEN / SUMMARY: - Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. METHODS: 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. FINDINGS: 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. INTERPRETATION: Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of medical complications and mortality, especially from age 40.

TÍTULO / TITLE:   - COVID-19 in patients with Down syndrome.

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REVISTA / JOURNAL:    - Neurol Sci. 2021 Feb 1:1-4. doi: 10.1007/s10072-021-05091-8.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s10072-021-05091-8

AUTORES / AUTHORS: - Emami A;et al.

INSTITUCIÓN / INSTITUTION: - Burn & Wound Healing Research Center, Department of Microbiology, Shiraz University of Medical Sciences, Shiraz, Iran. 

RESUMEN / SUMMARY: - PURPOSE: The aim of the current study was to determine whether COVID-19 is associated with a different presenting clinical picture or a more severe course of illness in people with Down syndrome (DS). METHODS: All consecutive patients who were admitted at healthcare facilities anywhere in Fars province (located in the south of Iran with a population of 4,851,000 people) from 19 February 2020 to 20 November 2020 were included. For every patient with DS, three age- and sex-matched patients with COVID-19 and without any underlying medical conditions were selected as controls. RESULTS: During the study period, 37,968 patients were hospitalized with a diagnosis of COVID-19. Eighteen patients had DS. Patients with DS were significantly more likely to be intubated [7 patients (39%)] compared with those without DS [3 patients (6%)]; p = 0.002. Patients with DS significantly more often died of COVID-19 compared with the controls [8 (44.4%) vs. 1 (1.9%); odds ratio: 24.37; 95% confidence interval 2.39-247.94; p = 0.007]. CONCLUSION: Patients with DS are among the high-risk populations with respect to severe COVID-19 and should receive the vaccine as soon as possible. Furthermore, they should receive more intensive care if they get hospitalized with the illness.

TÍTULO / TITLE:   - Specific Susceptibility to COVID-19 in Adults with Down Syndrome.

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REVISTA / JOURNAL:    - Neuromolecular Med. 2021 Mar 4:1-11. doi: 10.1007/s12017-021-08651-5.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s12017-021-08651-5

AUTORES / AUTHORS: - Illouz T;et al.... Strydom A

INSTITUCIÓN / INSTITUTION: - The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, 5290002, Ramat-Gan, Israel.The Paul Feder Laboratory On Alzheimer’s Disease Research, Bar-Ilan University, 5290002, Ramat-Gan, Israel. 

RESUMEN / SUMMARY: - The current SARS-CoV-2 outbreak, which causes COVID-19, is particularly devastating for individuals with chronic medical conditions, in particular those with Down Syndrome (DS) who often exhibit a higher prevalence of respiratory tract infections, immune dysregulation and potential complications. The incidence of Alzheimer’s disease (AD) is much higher in DS than in the general population, possibly increasing further the risk of COVID-19 infection and its complications. Here we provide a biological overview with regard to specific susceptibility of individuals with DS to SARS-CoV-2 infection as well as data from a recent survey on the prevalence of COVID-19 among them. We see an urgent need to protect people with DS, especially those with AD, from COVID-19 and future pandemics and focus on developing protective measures, which also include interventions by health systems worldwide for reducing the negative social effects of long-term isolation and increased periods of hospitalization.

TÍTULO / TITLE:   - Down syndrome with neonatal alloimmune thrombocytopenia due to anti-HLA A31 and B61 antibodies.

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REVISTA / JOURNAL:    - Int J Hematol. 2021 Feb 11. doi: 10.1007/s12185-021-03092-z.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s12185-021-03092-z

AUTORES / AUTHORS: - Shima E;et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan. 

RESUMEN / SUMMARY: - Neonatal alloimmune thrombocytopenia (NAIT) arises from fetomaternal platelet incompatibility that results in transplacental passage of maternal antibodies mostly against fetal human platelet antigens (HPA), whereas NAIT due to anti-human leukocyte antigen (HLA) antibodies is extremely rare. Here, we report a case of Down syndrome (DS) with NAIT that was attributed to HLA antibodies. A boy with DS was delivered at 36 weeks’ gestation. His platelet count declined to 13.0 × 10(9)/L, suggestive of NAIT rather than other conditions, including transient abnormal myelopoiesis. Random platelet concentrates and intravenous immunoglobulin administration resolved the thrombocytopenia without clinical complications. Immunoserological investigations detected anti-HLA, but no anti-HPA antibodies in samples from the patient and the mother. HLA typing and cross-matching indicated that anti-HLA antibodies to paternal HLA A31 and B61, which had probably been induced during a prior pregnancy, led to NAIT in this case. Although it is a rare condition, healthcare providers should consider NAIT due to HLA antibodies and be vigilant for subsequent cases in DS.

Molecular biology/Biochemistry - Biología molecular/Bioquímica

TÍTULO / TITLE:   - Insulin resistance, oxidative stress and mitochondrial defects in Ts65dn mice brain: A harmful synergistic path in down syndrome.

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REVISTA / JOURNAL:    - Free Radic Biol Med. 2021 Mar;165:152-170. doi: 10.1016/j.freeradbiomed.2021.01.042. Epub 2021 Jan 2

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.freeradbiomed.2021.01.042

AUTORES / AUTHORS: - Lanzillotta C;... Barone E;

INSTITUCIÓN / INSTITUTION: - Department of Biochemical Sciences “A. Rossi-Fanelli”, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Roma, Italy.  

RESUMEN / SUMMARY: - Dysregulation of brain insulin signaling with reduced downstream neuronal survival and plasticity mechanisms are fundamental abnormalities observed in Alzheimer disease (AD). This phenomenon, known as brain insulin resistance, is associated with poor cognitive performance and is driven by the inhibition of IRS1. Since Down syndrome (DS) and AD neuropathology share many common features, we investigated metabolic aspects of neurodegeneration in DS and whether they contribute to early onset AD in DS. We evaluated levels and activation of proteins belonging to the insulin signaling pathway (IR, IRS1, BVR-A, MAPK, PTEN, Akt, GSK3β, PKCζ, AS160, GLUT4) in the frontal cortex of Ts65dn (DS model) (n = 5-6/group) and euploid mice (n = 6/group) at different ages (1, 3, 9 and 18 months). Furthermore, we analyzed whether changes of brain insulin signaling were associated with alterations of: (i) proteins regulating brain energy metabolism (mitochondrial complexes, hexokinase-II, Sirt1); (ii) oxidative stress (OS) markers (iii) APP cleavage; and (iv) proteins mediating synaptic plasticity mechanisms (PSD95, syntaxin-1 and BDNF). Ts65dn mice showed an overall impairment of the above-mentioned pathways, mainly characterized by defects of proteins activation state. Such alterations start early in life (at 1 month, during brain maturation). In particular, accumulation of inhibited IRS1, together with the uncoupling among the proteins downstream from IRS1 (brain insulin resistance), characterize Ts65dn mice. Furthermore, reduced levels of mitochondrial complexes and Sirt1, as well as increased indices of OS also were observed. These alterations precede the accumulation of APP-C99 in Ts65dn mice. Tellingly, oxidative stress levels were negatively associated with IR, IRS1 and AS160 activation as well as mitochondrial complexes levels in Ts65dn mice, suggesting a role for oxidative stress in the observed alterations. We propose that a close link exists among brain insulin resistan

TÍTULO / TITLE:   - Amniotic fluid metabolic fingerprinting indicated metabolites which may play a role in the pathogenesis of foetal Down syndrome - a preliminary report.

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REVISTA / JOURNAL:    - Ginekol Pol. 2021 Feb 12. doi: 10.5603/GP.a2020.0174.

Enlace a la Editora de la Revista http://dx.doi.org/10.5603/GP.a2020.0174

AUTORES / AUTHORS: - Parfieniuk E et al

INSTITUCIÓN / INSTITUTION: - Metabolomics Laboratory, Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland 

RESUMEN / SUMMARY: - Down syndrome is the most common human chromosomal aberration. It is commonly known that it is a genetic- based disease, but still, pathomechanisms which lead to observed disorders have not been explained. The objective of this study was to determine the metabolic fingerprinting of the amniotic fluid women carrying foetuses with Down syndrome (DS). MATERIAL AND METHODS: The study and control groups consisted of women who underwent routine amniocentesis between the 15th and 18th week of gestation. After analysis of the karyotyping results, 13 women with foetal DS were chosen. For the control group, 13 healthy patients with uncomplicated pregnancies who delivered healthy newborns at term was selected. Amniotic fluid was analyzed using liquid chromatography combined with high resolution mass spectrometry. RESULTS: In the amniotic fluid of women with foetal DS compared to patients with healthy foetuses, we reported significant differences in the level of four metabolites: methylhistidine, hexanoylcarnitine, diacetylspermine and p-cresol sulfate which may be connected with improper development of nervous system and muscles. We detected bacterial metabolite, which support the latest thesis about non-sterile intrauterine environment. CONCLUSIONS: Based on our findings, we hypothesise that differences in the level of four metabolites in the amniotic fluid may play role in the pathogenesis of DS. Defining their potential as biochemical pathogenic factors of DS requires further investigation of the biological pathways involving in the foetal development.

TÍTULO / TITLE:   - Lipid profile of Mexican children with Down syndrome.

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REVISTA / JOURNAL:    - BMC Pediatr. 2021 Feb 13;21(1):77. doi: 10.1186/s12887-021-02542-1.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s12887-021-02542-1

AUTORES / AUTHORS: - Garcia-de la Puente S; et al

INSTITUCIÓN / INSTITUTION: - Pediatrician. Down Syndrome Clinic, Instituto Nacional de Pediatría, Ciudad de México, Mexico. 

RESUMEN / SUMMARY: - Down syndrome (DS) is associated with various congenital anomalies and metabolic alterations, such as dyslipidemias, that can lead to cardiovascular disease in adulthood. This study was designed to describe the lipid concentrations and the frequency of dyslipidemias in children with DS. MATERIALS AND METHODS: The sample included 386 patients, 52.4% male. The study was carried out on children with DS, aged 2-18 years old, who were patients at the Mexican National Institute of Pediatrics between May 2016 and June 2017. Their height and weight were recorded, and their serum cholesterol, HDL cholesterol, and triglyceride levels were determined. RESULTS: Of the total patients included, 57.5% had some type of dyslipidemia, 32.6% isolated and 24.9% combined. The most common alteration, considering both isolated and combined dyslipidemias, was low HDL, in 45.9%, followed by hypertriglyceridemia, in 26.2%. Among those with combined dyslipidemia, high TG with low HDL-c was the most common, in 17.9%. A significant association was found between dyslipidemia and obesity, as well as between dyslipidemia and central obesity. The percentiles of lipid values are reported. CONCLUSION: The presence of an unfavorable lipid profile is common in pediatric patients with Down syndrome, especially low HDL cholesterol and high triglycerides.

TÍTULO / TITLE:   - Down syndrome is an oxidative phosphorylation disorder.

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REVISTA / JOURNAL:    - Redox Biol. 2021 Jan 22;41:101871. doi: 10.1016/j.redox.2021.101871.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.redox.2021.101871

AUTORES / AUTHORS: - Bayona-Bafaluy MP;... Ruiz-Pesini E;

INSTITUCIÓN / INSTITUTION: - Departamento de Bioquí­mica, Biologí­a Molecular y Celular, Universidad de Zaragoza, C/ Miguel Servet, 177. 50013, Zaragoza, España 

RESUMEN / SUMMARY: - Down syndrome is the most common genomic disorder of intellectual disability and is caused by trisomy of chromosome 21. Several genes in this chromosome repress mitochondrial biogenesis. The goal of this study was to evaluate whether early overexpression of these genes may cause a prenatal impairment of oxidative phosphorylation negatively affecting neurogenesis. Reduction in the mitochondrial energy production and a lower mitochondrial function have been reported in diverse tissues or cell types, and also at any age, including early fetuses, suggesting that a defect in oxidative phosphorylation is an early and general event in Down syndrome individuals. Moreover, many of the medical conditions associated with Down syndrome are also frequently found in patients with oxidative phosphorylation disease. Several drugs that enhance mitochondrial biogenesis are nowadays available and some of them have been already tested in mouse models of Down syndrome restoring neurogenesis and cognitive defects. Because neurogenesis relies on a correct mitochondrial function and critical periods of brain development occur mainly in the prenatal and early neonatal stages, therapeutic approaches intended to improve oxidative phosphorylation should be provided in these periods.

TÍTULO / TITLE:   - Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome.

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REVISTA / JOURNAL:    - Sci Adv. 2021 Feb 12;7(7):eabe5085. doi: 10.1126/sciadv.abe5085. Print 2021 Feb.

Enlace a la Editora de la Revista http://dx.doi.org/10.1126/sciadv.abe5085

AUTORES / AUTHORS: - DAcunzo P et al.

INSTITUCIÓN / INSTITUTION: - Center for Dementia Research, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA. 

RESUMEN / SUMMARY: - Mitochondrial dysfunction is an established hallmark of aging and neurodegenerative disorders such as Down syndrome (DS) and Alzheimer’s disease (AD). Using a high-resolution density gradient separation of extracellular vesicles (EVs) isolated from murine and human DS and diploid control brains, we identify and characterize a previously unknown population of double-membraned EVs containing multiple mitochondrial proteins distinct from previously described EV subtypes, including microvesicles and exosomes. We term these newly identified mitochondria-derived EVs “mitovesicles.” We demonstrate that brain-derived mitovesicles contain a specific subset of mitochondrial constituents and that their levels and cargo are altered during pathophysiological processes where mitochondrial dysfunction occurs, including in DS. The development of a method for the selective isolation of mitovesicles paves the way for the characterization in vivo of biological processes connecting EV biology and mitochondria dynamics and for innovative therapeutic and diagnostic strategies.

TÍTULO / TITLE:   - Metabolic Diseases and Down Syndrome: How Are They Linked Together?

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REVISTA / JOURNAL:    - Biomedicines. 2021 Feb 22;9(2):221. doi: 10.3390/biomedicines9020221.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/biomedicines9020221

AUTORES / AUTHORS: - Moreau M;et al.

INSTITUCIÓN / INSTITUTION: - Laboratoire Processus Dégénératifs, Université de Paris, BFA, UMR 8251, CNRS, Stress et Vieillissemen, F-75013 Paris, France. 

RESUMEN / SUMMARY: - Down syndrome is a genetic disorder caused by the presence of a third copy of chromosome 21, associated with intellectual disabilities. Down syndrome is associated with anomalies of both the nervous and endocrine systems. Over the past decades, dramatic advances in Down syndrome research and treatment have helped to extend the life expectancy of these patients. Improved life expectancy is obviously a positive outcome, but it is accompanied with the need to address previously overlooked complications and comorbidities of Down syndrome, including obesity and diabetes, in order to improve the quality of life of Down syndrome patients. In this focused review, we describe the associations between Down syndrome and comorbidities, obesity and diabetes, and we discuss the understanding of proposed mechanisms for the association of Down syndrome with metabolic disorders. Drawing molecular mechanisms through which Type 1 diabetes and Type 2 diabetes could be linked to Down syndrome could allow identification of novel drug targets and provide therapeutic solutions to limit the development of metabolic and cognitive disorders.

Neurobiology - Neurobiología

TÍTULO / TITLE:   - Nuclear Reorganization in hippocampal granule cells neurons from a mouse model of Down Syndrome: changes in chromatin configuration, nucleoli and Cajal bodies.

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REVISTA / JOURNAL:    - Int. J. Mol. Sci. 2021, 22, 1259. https://doi.org/10.3390/ijms22031259

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AUTORES / AUTHORS: - Puente-Bedia A ... Lafarga M, Rueda N

INSTITUCIÓN / INSTITUTION: - Dept. Physiology & Pharmacology, Fac. Medicine, Univ. Cantabria, Santander, Spain 

RESUMEN / SUMMARY: - Down syndrome (DS) or trisomy of chromosome 21 (Hsa21) is characterized by impaired hippocampal-dependent learning and memory. These alterations are due to defective neurogenesis and to neuromorphological and functional anomalies of numerous neuronal populations, including hippocampal granular cells (GCs). It has been proposed that the additional gene dose in trisomic cells induces modifications in nuclear compartments and on the chromatin landscape, which could contribute to some DS phenotypes. The Ts65Dn (TS) mouse model of DS carries a triplication of 92 genes orthologous to those found in Hsa21, and shares many phenotypes with DS individuals, including cognitive and neuromorphological alterations. Considering its essential role in hippocampal memory formation, we investigated whether the triplication of this set of Hsa21 orthologous genes in TS mice modifies the nuclear architecture of their GCs. Our results show that the TS mouse presents alterations in the nuclear architecture of its GCs, affecting nuclear compartments involved in transcription and pre-rRNA and pre-mRNA processing. In particular, the GCs of the TS mouse show alterations in the nucleolar fusion pattern and the molecular assembly of Cajal bodies (CBs). Furthermore, hippocampal GCs of TS mice present an epigenetic dysregulation of chromatin that results in an increased heterochromatinization and reduced global transcriptional activity. These nuclear alterations could play an important role in the neuromorphological and/or functional alterations of the hippocampal GCs implicated in the cognitive dysfunction characteristic of TS mice.

TÍTULO / TITLE:   - Loss-of-function mutation of c-Ret causes cerebellar hypoplasia in mice with Hirschsprung disease and Down’s syndrome.

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REVISTA / JOURNAL:    - J Biol Chem. 2021 Feb 6;296:100389. doi: 10.1016/j.jbc.2021.100389.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jbc.2021.100389

AUTORES / AUTHORS: - Ohgami N;... Kato M;

INSTITUCIÓN / INSTITUTION: - Departments of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan; Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Science 

RESUMEN / SUMMARY: - The c-RET proto-oncogene encodes a receptor-tyrosine kinase. Loss-of-function mutations of RET have been shown to be associated with Hirschsprung disease and Down’s syndrome (HSCR-DS) in humans. DS is known to involve cerebellar hypoplasia, which is characterized by reduced cerebellar size. Despite the fact that c-Ret has been shown to be associated with HSCR-DS in humans and to be expressed in Purkinje cells (PCs) in experimental animals, there is limited information about the role of activity of c-Ret/c-RET kinase in cerebellar hypoplasia. We found that a loss-of-function mutation of c-Ret Y1062 in PCs causes cerebellar hypoplasia in c-Ret mutant mice. Wild-type mice had increased phosphorylation of c-Ret in PCs during postnatal development, while c-Ret mutant mice had postnatal hypoplasia of the cerebellum with immature neurite outgrowth in PCs and granule cells (GCs). c-Ret mutant mice also showed decreased numbers of glial fibers and mitogenic sonic hedgehog (Shh)-positive vesicles in the external germinal layer of PCs. c-Ret-mediated cerebellar hypoplasia was rescued by subcutaneous injection of a Smoothened agonist (SAG) as well as by reduced expression of Patched1, a negative regulator for Shh. Our results suggest that the loss-of-function mutation of c-Ret Y1062 results in the development of cerebellar hypoplasia via impairment of the Shh-mediated development of GCs and glial fibers in mice with HSCR-DS.

TÍTULO / TITLE:   - Multi-influential genetic interactions alter behaviour and cognition through six main biological cascades in Down syndrome mouse models.

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REVISTA / JOURNAL:    - Hum Mol Genet. 2021 Mar 9:ddab012. doi: 10.1093/hmg/ddab012.

Enlace a la Editora de la Revista http://dx.doi.org/10.1093/hmg/ddab012

AUTORES / AUTHORS: - Duchon A;et al.

INSTITUCIÓN / INSTITUTION: - Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), department of translational medicine and neurogenetics 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France. 

RESUMEN / SUMMARY: - Down syndrome (DS) is the most common genetic form of intellectual disability caused by the presence of an additional copy of human chromosome 21 (Hsa21). To provide novel insights into genotype-phenotype correlations, we used standardized behavioural tests, magnetic resonance imaging (MRI) and hippocampal gene expression to screen several DS mouse models for the mouse chromosome 16 region homologous to Hsa21. First, we unravelled several genetic interactions between different regions of chromosome 21 and how they contribute significantly to altering the outcome of the phenotypes in brain cognition, function and structure. Then, in-depth analysis of misregulated expressed genes involved in synaptic dysfunction highlighted 6 biological cascades centered around DYRK1A, GSK3β, NPY, SNARE, RHOA and NPAS4. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms targeting specific hubs in DS models that should become central to better understanding of DS and improving the development of therapies.

TÍTULO / TITLE:   - Genome-wide hyper-methylation is closely associated with abnormal expression of genes involved in neural development in induced pluripotent stem cells derived from a Down Syndrome mouse model.

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REVISTA / JOURNAL:    - Cell Biol Int. 2021 Feb 1. doi: 10.1002/cbin.11560.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/cbin.11560

AUTORES / AUTHORS: - Xi JJ;et al.

INSTITUCIÓN / INSTITUTION: - Shanghai Institute of Medical Genetics, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, 200040, China. 

RESUMEN / SUMMARY: - Mental retardation is the main clinical manifestation of Down syndrome (DS), and neural abnormalities occur during the early embryonic period and continue throughout life. Tc1, a model mouse for DS, carries the majority part of the human chromosome 21 and has multiple neuropathy phenotypes similar to patients with DS. To explore the mechanism of early neural abnormalities of Tc1 mouse, induced pluripotent stem (iPS) cells from Tc1 were obtained, and genome-wide gene expression and methylation analysis were performed for Tc1 and wild type mouse iPS cells. Our results showed hyper-methylation profiles for Tc1 iPS cells, and the abnormal genes were shown to be related to neurodevelopment and distributed on multiple chromosomes. In addition, important genes involved in neurogenesis and neurodevelopment were shown to be down-regulated in Tc1 iPS cells. In short, our study indicated that genome-wide hyper-methylation leads to disordered expression of genes associated with neurodevelopmental in the early development in Tc1mouse. Overall, our work provided a useful reference for the study of molecular mechanism of nervous system abnormalities in DS. 

TÍTULO / TITLE:   - Neurometabolite mapping highlights elevated myo-inositol profiles within the developing brain in down syndrome

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REVISTA / JOURNAL:    - Neurobiol Dis. 2021 Jun;153:105316. doi: 10.1016/j.nbd.2021.105316. Epub 2021 Mar 9.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.nbd.2021.105316

AUTORES / AUTHORS: - Patkee PA;... De Vita E;

INSTITUCIÓN / INSTITUTION: - Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, St. Thomas’ Hospital, London SE1 7EH, UK; Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Scie 

RESUMEN / SUMMARY: - The neurodevelopmental phenotype in Down Syndrome (DS), or Trisomy 21, is variable including a wide spectrum of cognitive impairment and a high risk of early-onset Alzheimer’s disease (AD). A key metabolite of interest within the brain in DS is Myo-inositol (mIns). The NA+/mIns co-transporter is located on human chromosome 21 and is overexpressed in DS. In adults with DS, elevated brain mIns was previously associated with cognitive impairment and proposed as a risk marker for progression to AD. However, it is unknown if brain mIns is increased earlier in development. The aim of this study was to estimate mIns concentration levels and key brain metabolites [N-acetylaspartate (NAA), Choline (Cho) and Creatine (Cr)] in the developing brain in DS and aged-matched controls. We used in vivo magnetic resonance spectroscopy (MRS) in neonates with DS (n = 12) and age-matched controls (n = 26) scanned just after birth (36-45 weeks postmenstrual age). Moreover, we used Mass Spectrometry in early (10-20 weeks post conception) ex vivo fetal brain tissue samples from DS (n = 14) and control (n = 30) cases. Relative to [Cho] and [Cr], we report elevated ratios of [mIns] in vivo in the basal ganglia/thalamus, in neonates with DS, when compared to age-matched typically developing controls. Glycine concentration ratios [Gly]/[Cr] and [Cho]/[Cr] also appear elevated. We observed elevated [mIns] in the ex vivo fetal cortical brain tissue in DS compared with controls. In conclusion, a higher level of brain mIns was evident as early as 10 weeks post conception and was measurable in vivo from 36 weeks post-menstrual age. Future work will determine if this early difference in metabolites is linked to cognitive outcomes in childhood or has utility as a potential treatment biomarker for early intervention.

TÍTULO / TITLE:   - One-carbon pathway and cognitive skills in children with Down syndrome.

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REVISTA / JOURNAL:    - Sci Rep. 2021 Feb 19;11(1):4225. doi: 10.1038/s41598-021-83379-7.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41598-021-83379-7

AUTORES / AUTHORS: - Antonaros F;et al.

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - This work investigates the role of metabolite levels in the intellectual impairment of subjects with Down syndrome (DS). Homocysteine, folate, vitamin B12, uric acid (UA), creatinine levels and MTHFR C677T genotype were analyzed in 147 subjects with DS. For 77 subjects, metabolite levels were correlated with cognitive tests. Griffiths-III test was administered to 28 subjects (3.08-6.16 years) and WPPSI-III test was administered to 49 subjects (7.08-16.08 years). Significant correlations were found among some metabolite levels and between homocysteine levels and MTHFR C677T genotype. Moreover, homocysteine, UA and creatinine levels resulted increased with age. We did not find any correlation between metabolites and cognitive test score in the younger group. Homocysteine showed statistically significant correlation with WPPSI-III subtest scores when its level is ≥ 7.35 µmol/L, remaining correlated in higher thresholds only for non-verbal area scores. Vitamin B12 showed correlations with all WPPSI-III subtest scores when its level is < 442 pg/mL. The relevance of the present findings is the detection of a specific metabolite threshold related with a better or worse cognitive score, suggesting that vitamin B12 and homocysteine may have a role in cognitive development in children with DS.

TÍTULO / TITLE:   - Subtle Roles of Down Syndrome Cell Adhesion Molecules in Embryonic Forebrain Development and Neuronal Migration.

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REVISTA / JOURNAL:    - Front Cell Dev Biol. 2021 Jan 28;8:624181. doi: 10.3389/fcell.2020.624181. eCollection 2020.

Enlace a la Editora de la Revista http://dx.doi.org/10.3389/fcell.2020.624181

AUTORES / AUTHORS: - Mitsogiannis MD;et al.

INSTITUCIÓN / INSTITUTION: - Developmental Neurobiology Group, Animal Physiology and Neurobiology Division, Department of Biology, Katholieke Universiteit Leuven, Leuven, Belgium. 

RESUMEN / SUMMARY: - Down Syndrome (DS) Cell Adhesion Molecules (DSCAMs) are transmembrane proteins of the immunoglobulin superfamily. Human DSCAM is located within the DS critical region of chromosome 21 (duplicated in Down Syndrome patients), and mutations or copy-number variations of this gene have also been associated to Fragile X syndrome, intellectual disability, autism, and bipolar disorder. The DSCAM paralogue DSCAM-like 1 (DSCAML1) maps to chromosome 11q23, implicated in the development of Jacobsen and Tourette syndromes. Additionally, a spontaneous mouse DSCAM deletion leads to motor coordination defects and seizures. Previous research has revealed roles for DSCAMs in several neurodevelopmental processes, including synaptogenesis, dendritic self-avoidance, cell sorting, axon growth and branching. However, their functions in embryonic mammalian forebrain development have yet to be completely elucidated. In this study, we revealed highly dynamic spatiotemporal patterns of Dscam and Dscaml1 expression in definite cortical layers of the embryonic mouse brain, as well as in structures and ganglionic eminence-derived neural populations within the embryonic subpallium. However, an in-depth histological analysis of cortical development, ventral forebrain morphogenesis, cortical interneuron migration, and cortical-subcortical connectivity formation processes in Dscam and Dscaml1 knockout mice (Dscam (del17) and Dscaml1 (GT) ) at several embryonic stages indicated that constitutive loss of Dscam and Dscaml1 does not affect these developmental events in a significant manner. Given that several Dscam- and Dscaml1-linked neurodevelopmental disorders are associated to chromosomal region duplication events, we furthermore sought to examine the neurodevelopmental effects of Dscam and Dscaml1 gain of function (GOF). In vitro, ex vivo, and in vivo GOF negatively impacted neural migration processes important to cortical development, and affected the morphology of maturing neurons. Overall, these

TÍTULO / TITLE:   - The flavonoid 7,8-DHF fosters prenatal brain proliferation potency in a mouse model of Down syndrome.

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REVISTA / JOURNAL:    - Sci Rep. 2021 Mar 18;11(1):6300. doi: 10.1038/s41598-021-85284-5.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41598-021-85284-5

AUTORES / AUTHORS: - Stagni F;... Guidi S

INSTITUCIÓN / INSTITUTION: - Department of Biomedical and Neuromotor Sciences, Physiology Building, University of Bologna, Piazza di Porta San Donato 2, 40126, Bologna, BO, Italy.  

RESUMEN / SUMMARY: - Neurogenesis impairment is a key determinant of intellectual disability in Down syndrome (DS), a genetic pathology due to triplication of chromosome 21. Since neurogenesis ceases after birth, apart in the hippocampus and olfactory bulb, the only means to tackle the problem of neurogenesis impairment in DS at its root is to intervene during gestation. A few studies in DS mouse models show that this is possible, although the drugs used may raise caveats in terms of safety. We previously found that neonatal treatment with 7,8-dihydroxyflavone (7,8-DHF), a flavonoid present in plants, restores hippocampal neurogenesis in the Ts65Dn model of DS. The goal of the current study was to establish whether prenatal treatment with 7,8-DHF improves/restores overall brain proliferation potency. Pregnant Ts65Dn females received 7,8-DHF from embryonic day 10 until delivery. On postnatal day 2 (P2) the pups were injected with BrdU and were killed after either 2 h or 52-60 days (P52-60). Evaluation of the number of proliferating (BrdU+) cells in various forebrain neurogenic niches of P2 mice showed that in treated Ts65Dn mice proliferation potency was improved or even restored in most of the examined regions, including the hippocampus. Quantification of the surviving BrdU+ cells in the dentate gyrus of P52-60 mice showed no difference between treated and untreated Ts65Dn mice. At P52-60, however, treated Ts65Dn mice exhibited a larger number of granule cells in comparison with their untreated counterparts, although their number did not reach that of euploid mice. Results show that 7,8-DHF has a widespread impact on prenatal proliferation potency in Ts65Dn mice and exerts mild long-term effects. It remains to be established whether treatment extending into the neonatal period can lead to an improvement in brain development that is retained in adulthood.

TÍTULO / TITLE:   - Signalling pathways contributing to learning and memory deficits in the Ts65Dn mouse model of Down syndrome.

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REVISTA / JOURNAL:    - Neuronal Signal. 2021 Mar 12;5(1):NS20200011. doi: 10.1042/NS20200011. eCollection 2021 Apr.

Enlace a la Editora de la Revista http://dx.doi.org/10.1042/NS20200011

AUTORES / AUTHORS: - Freeburn A;Munn RGK

INSTITUCIÓN / INSTITUTION: - Discipline of Pharmacology and Therapeutics, National University of Ireland, Galway, Republic of Ireland. 

RESUMEN / SUMMARY: - Down syndrome (DS) is a genetic trisomic disorder that produces life-long changes in physiology and cognition. Many of the changes in learning and memory seen in DS are reminiscent of disorders involving the hippocampal/entorhinal circuit. Mouse models of DS typically involve trisomy of murine chromosome 16 is homologous for many of the genes triplicated in human trisomy 21, and provide us with good models of changes in, and potential pharmacotherapy for, human DS. Recent careful dissection of the Ts65Dn mouse model of DS has revealed differences in key signalling pathways from the basal forebrain to the hippocampus and associated rhinal cortices, as well as changes in the microstructure of the hippocampus itself. In vivo behavioural and electrophysiological studies have shown that Ts65Dn animals have difficulties in spatial memory that mirror hippocampal deficits, and have changes in hippocampal electrophysiological phenomenology that may explain these differences, and align with expectations generated from in vitro exploration of this model. Finally, given the existing data, we will examine the possibility for pharmacotherapy for DS, and outline the work that remains to be done to fully understand this system.

Neurology - Neurología

TÍTULO / TITLE:   - Treatment outcomes for infantile spasms in Japanese children with Down Syndrome.

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REVISTA / JOURNAL:    - Pediatr Int. 2021 Feb 26. doi: 10.1111/ped.14668.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/ped.14668

AUTORES / AUTHORS: - Nishimoto S;et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki-city, Osaka, 569-8686, Japan. 

RESUMEN / SUMMARY: - To assess the treatment response to conventional antiepileptic drugs and low-dose ACTH therapy for infantile spasms in children with Down syndrome. METHODS: We retrospectively investigated the response and relapse rates, electroencephalography findings, patient characteristics during drug withdrawal, and developmental outcome in 10 children with Down syndrome treated for infantile spasms in our hospital. RESULTS: All patients showed cessation of infantile spasms and achieved electroencephalographic normalization. Spasm relapse occurred in one of 10 patients (10%). Antiepileptic drugs have been withdrawn for seven of 10 patients (70%), none of whom have experienced seizure relapse since drug withdrawal. The median developmental quotient (n=8) was 20.5, which shows that the developmental outcome was unfavorable. Low-dose ACTH therapy achieved a low seizure remission rate of 28.6%. CONCLUSIONS: Elucidation of the optimal treatment for infantile spasms in children with Down syndrome is needed to reduce the duration of infantile spasms and improve the developmental outcome.

TÍTULO / TITLE:   - Structural equation models to estimate dynamic effective connectivity networks in resting fMRI. A comparison between individuals with Down syndrome and controls.

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REVISTA / JOURNAL:    - Behav Brain Res. 2021 May 7;405:113188. doi: 10.1016/j.bbr.2021.113188. Epub 2021 Feb 23.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.bbr.2021.113188

AUTORES / AUTHORS: - Figueroa-Jimnez MD;... Guardia-Olmos J;

INSTITUCIÓN / INSTITUTION: - Department of Social Psychology & Quantitative Psychology Faculty of Psychology, University of Barcelona, España; UB Institute of Complex Systems, University of Barcelona, España; Institute of Neuroscience, University of Barcelona, España.  

RESUMEN / SUMMARY: - Emerging evidence suggests that an effective or functional connectivity network does not use a static process over time but incorporates dynamic connectivity that shows changes in neuronal activity patterns. Using structural equation models (SEMs), we estimated a dynamic component of the effective network through the effects (recursive and nonrecursive) between regions of interest (ROIs), taking into account the lag 1 effect. The aim of the paper was to find the best structural equation model (SEM) to represent dynamic effective connectivity in people with Down syndrome (DS) in comparison with healthy controls. Twenty-two people with DS were registered in a functional magnetic resonance imaging (fMRI) resting-state paradigm for a period of six minutes. In addition, 22 controls, matched by age and sex, were analyzed with the same statistical approach. In both groups, we found the best global model, which included 6 ROIs within the default mode network (DMN). Connectivity patterns appeared to be different in both groups, and networks in people with DS showed more complexity and had more significant effects than networks in control participants. However, both groups had synchronous and dynamic effects associated with ROIs 3 and 4 related to the upper parietal areas in both brain hemispheres as axes of association and functional integration. It is evident that the correct classification of these groups, especially in cognitive competence, is a good initial step to propose a biomarker in network complexity studies.

TÍTULO / TITLE:   - Computerized physical and cognitive training improves the functional architecture of the brain in adults with Down syndrome: A network science EEG study.

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REVISTA / JOURNAL:    - Netw Neurosci. 2021 Mar 1;5(1):274-294. doi: 10.1162/netn_a_00177. eCollection 2021.

Enlace a la Editora de la Revista http://dx.doi.org/10.1162/netn_a_00177

AUTORES / AUTHORS: - Anagnostopoulou A;et al.

INSTITUCIÓN / INSTITUTION: - Medical Physics Laboratory, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece. 

RESUMEN / SUMMARY: - Understanding the neuroplastic capacity of people with Down syndrome (PwDS) can potentially reveal the causal relationship between aberrant brain organization and phenotypic characteristics. We used resting-state EEG recordings to identify how a neuroplasticity-triggering training protocol relates to changes in the functional connectivity of the brain’s intrinsic cortical networks. Brain activity of 12 PwDS before and after a 10-week protocol of combined physical and cognitive training was statistically compared to quantify changes in directed functional connectivity in conjunction with psychosomatometric assessments. PwDS showed increased connectivity within the left hemisphere and from left-to-right hemisphere, as well as increased physical and cognitive performance. Our findings reveal a strong adaptive neuroplastic reorganization as a result of the training that leads to a less-random network with a more pronounced hierarchical organization. Our results go beyond previous findings by indicating a transition to a healthier, more efficient, and flexible network architecture, with improved integration and segregation abilities in the brain of PwDS. Resting-state electrophysiological brain activity is used here for the first time to display meaningful relationships to underlying Down syndrome processes and outcomes of importance in a translational inquiry. This trial is registered with ClinicalTrials.gov Identifier NCT04390321.

TÍTULO / TITLE:   - Sleep-related learning in Williams Syndrome and Down’s Syndrome.

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REVISTA / JOURNAL:    - Adv Child Dev Behav. 2021;60:261-283. doi: 10.1016/bs.acdb.2020.07.002. Epub 2021 Feb 11.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/bs.acdb.2020.07.002

AUTORES / AUTHORS: - Dimitriou D; Halstead EJ

INSTITUCIÓN / INSTITUTION: - Sleep Research and Education Laboratory, UCL Institute of Education, London, United Kingdom 

RESUMEN / SUMMARY: - This chapter addresses sleep research challenges for the study of neurodevelopmental disorders drawing upon two disorders such as Down Syndrome and Williams syndrome. General sleep problems are outlined here, however particular consideration is given to the syndrome-specific issues or challenges that may be crucial to advancing our understanding of sleep-related cognitive and behavioral issues.

TÍTULO / TITLE:   - Prevalence of Keratoconus in Persons With Down Syndrome in a National Registry in Norway.

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REVISTA / JOURNAL:    - JAMA. Free access to the article (immediately).Link the journalhttp://jama.ama-assn.org/search.dtl

Enlace a la Editora de la Revista http://dx.doi.org/10.1001/jamanetworkopen.2021.0814

AUTORES / AUTHORS: - Kristianslund O;Drolsum L

INSTITUCIÓN / INSTITUTION: - Department of Ophthalmology, Oslo University Hospital, Oslo, Norway.;  

RESUMEN / SUMMARY: - This cross-sectional study evaluates the association of keratoconus with Down syndrome by estimation of the prevalence of keratoconus in persons with Down syndrome in Norway.

TÍTULO / TITLE:   - Evidence of a Down Syndrome Keratopathy: A Three-Dimensional (3-D) Morphogeometric and Volumetric Analysis.

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REVISTA / JOURNAL:    - J Pers Med. 2021 Jan 30;11(2):82. doi: 10.3390/jpm11020082.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/jpm11020082

AUTORES / AUTHORS: - Toprak I et al.

INSTITUCIÓN / INSTITUTION: - Department of Research and Development, VISSUM, 03016 Alicante, España.;  

RESUMEN / SUMMARY: - The aim of this study was to investigate whether a different and abnormal corneal profile is present in Down syndrome (DS) by personalized three-dimensional (3D) modelling. This single-centre cross-sectional study included 43 patients with DS (43 eyes) and 58 age-sex-matched control subjects (58 eyes) with normal karyotype and topography. Refraction, central corneal thickness (CCT), aberrations (high-order, coma and spherical), asphericity and morphogeometric/volumetric parameters based on a 3D corneal model that was generated from raw topographical data were evaluated. Deviation of anterior/posterior apex (D(apexant)/D(apexpost)) and thinnest point (D(mctant)/D(mctpost)) from corneal vertex, anterior/posterior surface area (A(ant)/A(post)), sagittal area passing through the anterior/posterior apex (A(apexant)/A(apexpost)) and thinnest point (A(mctpost)), total corneal volume (V(total)) and volumetric progression for each 0.05 mm step of the radius value centred to the thinnest point (VOL(MCT)) and anterior/posterior apex (VOL(AAP)/VOL(PAP)) comprised the morphogeometric/volumetric parameters. In the DS group, 58.1% of the eyes presented abnormal topography. High-order and coma aberrations, asphericity, D(apexant), A(ant), A(post) and A(apexant) were significantly higher, whereas CCT, A(apexpost), A(mctpost), V(total), VOL(AAP), VOL(PAP) and VOL(MCT) were lower in the DS group than in the control group (p < 0.05). D(apexpost) did not differ between the groups (p > 0.05). This study demonstrates that corneas of the subjects with DS are different and more aberrated than those of normal age- and sex-matched non-DS controls. Anterior corneal apex appears to be displaced in DS even with normal topography, while posterior apex seems stable although topography is abnormal. These findings may help to modify our approach in the diagnosis of keratopathy in subjects with DS.

Ophtalmology - Oftalmología

TÍTULO / TITLE:   - Aqueous Misdirection After Trabeculectomy in a Down Syndrome Patient with Angle-closure Glaucoma.

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REVISTA / JOURNAL:    - J Glaucoma. 2021 Mar 12. doi: 10.1097/IJG.0000000000001831.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/IJG.0000000000001831

AUTORES / AUTHORS: - Fox A;et al.

INSTITUCIÓN / INSTITUTION: - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA Institute for Vision Research. 

RESUMEN / SUMMARY: - Down syndrome is a genetic disease caused by trisomy of chromosome 21 that is characterized by numerous systemic abnormalities including intellectual disability, stereotypical facies, and congenital heart malformations. Ocular abnormalities are commonly seen with Down syndrome including corneal disease (keratoconus), refractive error, and atypical irides (Brushfield spots). We report the first case of aqueous misdirection in a patient with Down syndrome after trabeculectomy. Patients with Down syndrome often have small, hyperopic eyes with narrow iridocorneal angles and may be at increased risk for aqueous misdirection associated with surgical procedures. Awareness of this risk may aid surgical planning and post-operative management.

Orthopedics - Ortopedía

TÍTULO / TITLE:   - JAK inhibition for treatment of psoriatic arthritis in Down syndrome.

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REVISTA / JOURNAL:    - Rheumatology (Oxford). 2021 Feb 25:keab203. doi: 10.1093/rheumatology/keab203.

Enlace a la Editora de la Revista http://dx.doi.org/10.1093/rheumatology/keab203

AUTORES / AUTHORS: - Pham AT;et al

INSTITUCIÓN / INSTITUTION: - Linda Crnic Institute for Down Syndrome. 

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - The relationship between atlas hypoplasia and os odontoideum in children with Down syndrome: a preliminary case report.

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REVISTA / JOURNAL:    - J Pediatr Orthop B. 2021 Mar 18. doi: 10.1097/BPB.0000000000000865.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/BPB.0000000000000865

AUTORES / AUTHORS: - Fujimoto Y;et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatric orthopedics, Shizuoka Children’s Hospital, Shizuoka Department of Orthopaedic Surgery, Yokohama Rosai Hospital, Kanagawa Department of Orthopaedic Surgery, the University of Tokyo, Tokyo, Japan. 

RESUMEN / SUMMARY: - The purpose of this study was to evaluate the relationship of os odontoideum and the size of atlas among children with Down syndrome. Understanding the risk of developing myelopathy in asymptomatic cases is important in children with Down syndrome. Children with os odontoideum are considered to be at high risk of developing myelopathy because of instability; however, in cases that are complicated by atlas hypoplasia, the risk remains the same, regardless of instability. This retrospective case-control study assessed atlas hypoplasia in children with Down syndrome with or without os odontoideum. We retrospectively assessed the records of 59 patients (36 males and 23 females) with Down syndrome who underwent spinal X-ray evaluations at our hospital. The average age at examination was 5.0 years (range, 4-7). We evaluated the following radiologically: the presence of os odontoideum; atlas-dens interval; space available for the spinal cord at the atlas level (C1SAC); instability index; sagittal atlas diameter (SAD) as an index of atlas hypoplasia and C5 level SAC (C5SAC), adjusted for child growth. Os odontoideum was present in seven cases (12%). Between the groups with and without os odontoideum, there was no significant difference in age (mean, 5.2 vs. 5.0 years) or male/female ratio (57 vs. 62% males). The SAD/C5SAC (mean, 1.6 vs. 1.9) was significantly smaller in the group with os odontoideum than in those without os odontoideum. The instability index was not significantly different between the two groups. Children with Down syndrome and os odontoideum have small SAD. Evaluations for atlas hypoplasia are necessary.

Physiotherapy - Fisioterapia

TÍTULO / TITLE:   - Promoting participation in physical activity among children and adolescents with Down syndrome.

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REVISTA / JOURNAL:    - Phys Ther. 2021 Feb 1:pzab032. doi: 10.1093/ptj/pzab032.

Enlace a la Editora de la Revista http://dx.doi.org/10.1093/ptj/pzab032

AUTORES / AUTHORS: - Wentz EE;et al.

INSTITUCIÓN / INSTITUTION: - SUNY Upstate Medical University, Syracuse, NY United States. 

RESUMEN / SUMMARY: - Children with Down syndrome often have lower physical activity levels compared to their peers with typical development and face challenges such as medical co-morbidities, access issues and societal stigma, to being physically active. Physical therapists are experts in exercise prescription and physical activity and are thus uniquely qualified to successfully promote participation among children with Down syndrome in spite of inherent challenges. Our perspective is that a shift in physical therapy service delivery is needed. We suggest that physical therapists change the focus of their interventions for children with Down syndrome from underlying impairments such as low tone or joint laxity, or from developing motor skills in isolation and ‘correct’ movement patterns. Instead, physical therapists should allow the physical activity preferences and the environmental contexts of the children and adolescents they are working with to direct the treatment plan. In this way, physical therapy intervention becomes more child centered by concentrating on developing the specific skills and strategies required for success in the child’s preferred physical activity. In this paper, we consider the role of pediatric physical therapists in the United States, as well as in low- and middle- income countries, in promoting and monitoring physical activity in children with Down syndrome from infancy through adolescence. Examples of physical therapist interventions such as tummy time, movement exploration, treadmill training, bicycle riding and strength training are discussed, across infancy, childhood and adolescence, with a focus on how to successfully promote lifelong participation in physical activity.

TÍTULO / TITLE:   - Differences in foot dimensions between children and adolescents with and without Down syndrome.

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REVISTA / JOURNAL:    - Disabil Rehabil. 2021 Mar 11:1-8. doi: 10.1080/09638288.2021.1895897.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/09638288.2021.1895897

AUTORES / AUTHORS: - Hassan NM et al

INSTITUCIÓN / INSTITUTION: - Discipline of Podiatry, School of Allied Health, Human Services and Sport, La Trobe University, Victoria, Australia 

RESUMEN / SUMMARY: - This study compared the differences in foot dimensions between children with and without Down syndrome using three-dimensional (3D) foot scans. Methods: 51 children with and 51 children without Down syndrome had a 3D scan taken of their right foot to compare the absolute and normalised (for height or foot length) measurements. Results: Normalised foot length was shorter in children with Down syndrome (MD -11.62 mm, 95% CI -15.06 to -8.18, p < 0.001). When normalised for foot length, ball of foot length (MD 2.87 mm, 95% CI 1.17 to 4.58, p = 0.001), diagonal and horizontal foot width (MD 3.65 mm, 95% CI 1.65 to 5.66, p < 0.001; MD 4.80 mm, 95% CI 2.88 to 6.72, p < 0.001, respectively), ball and instep girth (MD 10.60 mm, 95% CI 5.96 to 15.25, p < 0.001; MD 7.92 mm, 95% CI 3.02 to 12.82, p = 0.002, respectively) and fifth toe height (MD 3.14 mm, 95% CI 2.22 to 4.07, p < 0.001) were greater in children with Down syndrome. Conclusions: Children with Down syndrome have shorter, wider feet with greater girth and fifthtoe height measurements relative to children without Down syndrome. These findings have implications for footwear fit and the manufacturing of population-specific footwear.IMPLICATIONS FOR REHABILITATIONFootwear-fitting issues arise as a result of the unique foot shape of children with Down syndrome.There are substantial variations in the foot shape of children with and without Down syndrome.Children with Down syndrome require wider, deeper footwear at a given length to accommodate their foot dimensions.These findings have implications for the manufacturing of population-specific footwear.

TÍTULO / TITLE:   - Current Trends in Pediatric Physical Therapy Practice for Children With Down Syndrome.

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REVISTA / JOURNAL:    - Pediatr Phys Ther. 2021 Apr 1;33(2):74-81. doi: 10.1097/PEP.0000000000000781.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/PEP.0000000000000781

AUTORES / AUTHORS: - ohnson R;et al.

INSTITUCIÓN / INSTITUTION: - School of Physical Therapy (Ms Johnson and Dr Looper), University of Puget Sound, Tacoma, Washington; School of Physical Therapy (Dr Fiss), Texas Woman’s University, Dallas, Texas. 

RESUMEN / SUMMARY: - Physical therapists (PTs) have a broad range of approaches to the management of Down syndrome (DS). PURPOSE: To examine the breadth of physical therapy practice for children with DS. METHODS: A survey was distributed to 1000 randomly selected members of the Academy of Pediatric Physical Therapy. DATA ANALYSIS: Responses were categorized into 13 thematic subcategories and 3 International Classification of Functioning, Disability and Health (ICF) subcategories. RESULTS AND DISCUSSION: One hundred eight PTs participated. Joint stability and alignment were the most common physical therapy-related problem. Functional movement was the most common physical therapy intervention. Most clinicians identified and treated at the ICF level of body functions and structure. Multiple assessment tools were used and tended to include norm-referenced tests. There was diversity of interventions with varying amounts of supporting evidence. CONCLUSIONS: PTs manage children with DS for a wide variety of needs with a variety of interventions.

TÍTULO / TITLE:   - Commentary on “Current Trends in Pediatric Physical Therapy Practice for Children With Down Syndrome”.

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REVISTA / JOURNAL:    - Pediatr Phys Ther. 2021 Apr 1;33(2):82. doi: 10.1097/PEP.0000000000000782.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/PEP.0000000000000782

AUTORES / AUTHORS: - Tekin F;Yarar F

INSTITUCIÓN / INSTITUTION: - School of Physical Therapy and Rehabilitation, Pamukkale University Denizli, Turkey. 

RESUMEN / SUMMARY: -

TÍTULO / TITLE:   - A Short-Term Resistance Training Circuit Improved Antioxidants in Sedentary Adults with Down Syndrome.

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REVISTA / JOURNAL:    - Oxid Med Cell Longev. 2021 Jan 19;2021:8811153. doi: 10.1155/2021/8811153. eCollection 2021.

Enlace a la Editora de la Revista http://dx.doi.org/10.1155/2021/8811153

AUTORES / AUTHORS: - Rosety-Rodriguez M et al

INSTITUCIÓN / INSTITUTION: - School of Medicine, University of Cadiz, Cadiz, Spain 

RESUMEN / SUMMARY: - Previous studies have found aerobic training improved oxidative damage in people with Down syndrome (DS). However, there is a lack of information regarding the influence of resistance training on redox imbalance in this population. Accordingly, this study was conducted to determine the effect of resistance training (RT) on antioxidant defence system in sedentary adults with DS. Thirty-six male adults with DS were recruited through different community support groups. Eighteen were randomly assigned to perform a circuit RT program with 6 stations, 3 days/week for 12 weeks. Plasma total antioxidant status (TAS), reduced glutathione (GHS), ascorbate, serum α-tocopherol, and erythrocyte glutathione reductase activity were assessed. Plasma malondialdehyde (MDA) and carbonyl groups (CG) were assessed as markers of oxidative damage. Muscle strength was also measured. Dynamic torque of knee extensors and flexors as well as maximal handgrip strength was significantly improved after the completion of the training program. Plasa levels of TAS and erythrocyte glutathione reductase (GR) activity were significantly increased. Conversely, MDA and CG levels were significantly reduced. It was concluded RT improved antioxidant defence system and reduced oxidative damage in adults with DS. Further, long-term studies are required to determine whether the increased antioxidant system may improve clinical outcomes of adults with DS.

Prenatal diagnosis - Diagnóstico

TÍTULO / TITLE:   - Trends in the prenatal diagnosis of trisomy 21 show younger maternal age and shift in the distribution of congenital heart disease over a 20-year period.

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REVISTA / JOURNAL:    - Am J Med Genet A. 2021 Mar 8. doi: 10.1002/ajmg.a.62162.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.62162

AUTORES / AUTHORS: - Tidrenczel Z... Beke A;

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary. 

RESUMEN / SUMMARY: - Prenatal testing has changed greatly over the past two decades, which may affect the diagnosis of congenital heart disease (CHD) in Down syndrome. The present study aimed to analyze changes in the prevalence and distribution of CHD diagnosed via ultrasonography and fetopathology in 462 fetuses with trisomy 21 between two consecutive 10-year periods (1999-2018), as well as the associations between CHDs, ultrasound markers, and extracardiac malformations. Overall, the frequency of cardiovascular malformations in trisomy 21 was 27.7 and 26.5%, and ultrasound identified 70 and 62% of CHDs during these periods. A profound increase in first-trimester ultrasound findings and associated anomalies with CHDs (ventricular septal defect, Tetralogy of Fallot) since 2009 were observed. Second-trimester nonstructural heart abnormalities were associated with ultrasound anomalies (74%) and major extracardiac malformations (42.9%). During both study periods, mothers carrying fetuses with CHD were significantly younger than those without CHD (p = 0.038, p = 0.009, respectively). Comparing the two 10-year periods, there were no changes in the prevalence and detection of CHDs. Trend analysis revealed that, although the frequency of CHD remained stable, the diagnostic spectrum had shifted between the study periods. Detection of nonstructural heart abnormalities necessitates detailed follow-up for cardiac/extracardiac malformations and chromosomal disorders.

TÍTULO / TITLE:   - Steroid profile analysis by liquid chromatography-tandem mass spectrometry in second-trimester pregnant women for trisomy 21 screening.

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REVISTA / JOURNAL:    - J Pharm Biomed Anal. 2021 Apr 15;197:113966. doi: 10.1016/j.jpba.2021.113966. Epub 2021 Feb 11.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jpba.2021.113966

AUTORES / AUTHORS: - Yuan TF;... Li Y;

INSTITUCIÓN / INSTITUTION: - Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China 

RESUMEN / SUMMARY: - Trisomy 21 is a serious chromosome abnormality. The conventional Down’s screening test is the most widely used for trisomy 21 screening. However, this method could lead to a higher false positive rate. Therefore, we aim to analyze steroid profile in second-trimester pregnant women and identify novel serum biomarkers of trisomy 21. METHODS: We employed an LC-MS/MS method to measure the steroid profile. The concentrations and product-to-substrate ratios in 71 second-trimester pregnant women were determined and statistically analyzed to identify novel biomarkers for trisomy 21 screening. RESULTS: We found that there were significant differences in levels of E3, 11-deoxycortisol, and 11-deoxycortisol /17-hydroxyprogesterone between two groups. The OPLS-DA plots revealed obvious separation between two groups. Combining VIP analysis (VIP > 1.0) with volcano plot (P < 0.05 and fold change >1.2 or < 0.83), 11-deoxycortisol was identified as a novel biomarker for trisomy 21. After controlling for confounders, we found 11-deoxycortisol was associated with trisomy 21 (adjusted P = 0.009), and the fully adjusted OR (95 % CI) was 0.098 (0.016-0.593) in highest quartile versus lowest quartile of 11-deoxycortisol (P = 0.011). CONCLUSIONS: Steroid profile analysis for the first time showed that steroid hormones perturbations occurred in pregnant women carrying a fetus affected by trisomy 21 and decreased 11-deoxycortisol levels were associated with trisomy 21.

Psychiatry - Psiquiatría

TÍTULO / TITLE:   - Deciphering the links between psychological stress, depression, and neurocognitive decline in patients with Down syndrome.

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REVISTA / JOURNAL:    - Neurobiol Stress. 2021 Feb 5;14:100305. doi: 10.1016/j.ynstr.2021.100305. eCollection 2021 May.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ynstr.2021.100305

AUTORES / AUTHORS: - Poumeaud F;et al.

INSTITUCIÓN / INSTITUTION: - Univ. Limoges, Peripheral Neuropathies, EA6309, F-87000, Limoges, France. 

RESUMEN / SUMMARY: - The relationships between psychological stress and cognitive functions are still to be defined despite some recent progress. Clinically, we noticed that patients with Down syndrome (DS) may develop rapid neurocognitive decline and Alzheimer’s disease (AD) earlier than expected, often shortly after a traumatic life event (bereavement over the leave of a primary caregiver, an assault, modification of lifestyle, or the loss of parents). Of course, individuals with DS are naturally prone to develop AD, given the triplication of chromosome 21. However, the relatively weak intensity of the stressful event and the rapid pace of cognitive decline after stress in these patients have to be noticed. It seems DS patients react to stress in a similar manner normal persons react to a very intense stress, and thereafter develop a state very much alike post-traumatic stress disorders. Unfortunately, only a few studies have studied stress-induced regression in patients with DS. Thus, we reviewed the biochemical events involved in psychological stress and found some possible links with cognitive impairment and AD. Interestingly, these links could probably be also applied to non-DS persons submitted to an intense stress. We believe these links should be further explored as a better understanding of the relationships between stress and cognition could help in many situations including individuals of the general population.

TÍTULO / TITLE:   - Stress Responses in Down Syndrome Neurodegeneration: State of the Art and Therapeutic Molecules.

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REVISTA / JOURNAL:    - Biomolecules. 2021 Feb 11;11(2):266. doi: 10.3390/biom11020266.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/biom11020266

AUTORES / AUTHORS: - Lanzillotta C; Di Domenico F

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Down syndrome (DS) is the most common genomic disorder characterized by the increased incidence of developing early Alzheimer’s disease (AD). In DS, the triplication of genes on chromosome 21 is intimately associated with the increase of AD pathological hallmarks and with the development of brain redox imbalance and aberrant proteostasis. Increasing evidence has recently shown that oxidative stress (OS), associated with mitochondrial dysfunction and with the failure of antioxidant responses (e.g., SOD1 and Nrf2), is an early signature of DS, promoting protein oxidation and the formation of toxic protein aggregates. In turn, systems involved in the surveillance of protein synthesis/folding/degradation mechanisms, such as the integrated stress response (ISR), the unfolded stress response (UPR), and autophagy, are impaired in DS, thus exacerbating brain damage. A number of pre-clinical and clinical studies have been applied to the context of DS with the aim of rescuing redox balance and proteostasis by boosting the antioxidant response and/or inducing the mechanisms of protein re-folding and clearance, and at final of reducing cognitive decline. So far, such therapeutic approaches demonstrated their efficacy in reverting several aspects of DS phenotype in murine models, however, additional studies aimed to translate these approaches in clinical practice are still needed.

TÍTULO / TITLE:   - Evaluating working memory outcome measures for children with Down syndrome.

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REVISTA / JOURNAL:    - J Intellect Disabil Res. 2021 Mar 25. doi: 10.1111/jir.12833.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jir.12833

AUTORES / AUTHORS: - Schworer EK et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USADivision of Behavioral Medicine and Clinical Psychology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA. 

RESUMEN / SUMMARY: - There is a critical need for the psychometric evaluation of outcome measures to be used in clinical trials targeting cognition in Down syndrome (DS). This study examines a specific cognitive skill that is of particular importance in DS, working memory, and the psychometric properties of a set of standardised measurements to assess working memory in individuals with DS. METHODS: Ninety children and adolescents ages 6 to 18 years old with DS were assessed on a selection of verbal and visuospatial working memory subtests of standardised clinical assessments at two time points to examine feasibility, distributional qualities, test-retest reliability and convergent validity against a priori criteria. Caregivers also completed an adaptive behaviour questionnaire to address working memory subtests’ associations with broader developmental functioning. RESULTS: The Stanford Binet-5 Verbal Working Memory, Differential Ability Scales-2 Recognition of Pictures, Stanford Binet-5 Nonverbal Working Memory and Wechsler Intelligence Scale for Children-5 Picture Span measures met the most psychometric criteria overall across the full age and IQ range of the study. Although Differential Ability Scales-2 Recall of Sequential Order and Differential Ability Scales-2 Recall of Digits Backward met the fewest a priori criteria, follow-up analyses suggested greater feasibility in specific age and IQ ranges. CONCLUSIONS: Several working memory measures appear to be psychometrically sound and appropriate for use in clinical trials for children with DS, especially when focusing on raw scores. However, floor effects on standard scores and feasibility of some measures were problematic. Guidelines for use of the working memory subtests with this population are provided.

TÍTULO / TITLE:   - Attention Bias and Prodromal Anxiety Symptoms in Toddlers With Fragile X Syndrome and Down Syndrome.

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REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2021 Mar 1;126(2):167-181. doi: 10.1352/1944-7558-126.2.167.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-126.2.167

AUTORES / AUTHORS: - Smith K;et al

INSTITUCIÓN / INSTITUTION: - Kayla Smith, Abigail L. Hogan, Elizabeth Will, and Jane E. Roberts, University of South Carolina. 

RESUMEN / SUMMARY: - Early identification of behavioral risk markers for anxiety is essential to optimize long-term outcomes in children with neurodevelopmental disorders. This study analyzed attentional avoidance and its relation to anxiety and autism spectrum disorder (ASD) symptomatology during social and nonsocial fear conditions in toddlers with fragile X syndrome (FXS) and Down syndrome (DS). Toddlers with FXS and DS exhibited increased nonsocial attentional avoidance relative to typically developing (TD) toddlers. Attentional avoidance was not related to anxiety symptom severity in any group; however, higher ASD symptom severity was related to more social attentional avoidance in the FXS and TD groups. Findings suggest that there may be different underlying mechanisms driving attentional avoidance across neurodevelopmental disorders.

TÍTULO / TITLE:   - A Meta-Analysis of Single-Case Research on Applied Behavior Analytic Interventions for People With Down Syndrome.

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REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2021 Mar 1;126(2):114-141. doi: 10.1352/1944-7558-126.2.114.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-126.2.114

AUTORES / AUTHORS: - Neil N;et al

INSTITUCIÓN / INSTITUTION: - Nicole Neil, Ashley Amicarelli, Brianna M. Anderson, and Kailee Liesemer, Western University, Canada. 

RESUMEN / SUMMARY: - This systematic review evaluates single-case research design studies investigating applied behavior analytic (ABA) interventions for people with Down syndrome (DS). One hundred twenty-five studies examining the efficacy of ABA interventions on increasing skills and/or decreasing challenging behaviors met inclusion criteria. The What Works Clearinghouse standards and Risk of Bias in N-of-1 Trials scale were used to analyze methodological characteristics, and Tau-U effect sizes were calculated. Results suggest the use of ABA-based interventions are promising for behavior change in people with DS. Thirty-six high-quality studies were identified and demonstrated a medium overall effect. A range of outcomes was targeted, primarily involving communication and challenging behavior. These outcomes will guide future research on ABA interventions and DS.

Quality of life - Calidad de vida

TÍTULO / TITLE:   - Computerized physical and cognitive training improves the functional architecture of the brain in adults with Down syndrome: A network science EEG study.

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REVISTA / JOURNAL:    - Netw Neurosci. 2021 Mar 1;5(1):274-294. doi: 10.1162/netn_a_00177. eCollection 2021.

Enlace a la Editora de la Revista http://dx.doi.org/10.1162/netn_a_00177

AUTORES / AUTHORS: - Anagnostopoulou A;et al.

INSTITUCIÓN / INSTITUTION: - Medical Physics Laboratory, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece. 

RESUMEN / SUMMARY: - Understanding the neuroplastic capacity of people with Down syndrome (PwDS) can potentially reveal the causal relationship between aberrant brain organization and phenotypic characteristics. We used resting-state EEG recordings to identify how a neuroplasticity-triggering training protocol relates to changes in the functional connectivity of the brain’s intrinsic cortical networks. Brain activity of 12 PwDS before and after a 10-week protocol of combined physical and cognitive training was statistically compared to quantify changes in directed functional connectivity in conjunction with psychosomatometric assessments. PwDS showed increased connectivity within the left hemisphere and from left-to-right hemisphere, as well as increased physical and cognitive performance. Our findings reveal a strong adaptive neuroplastic reorganization as a result of the training that leads to a less-random network with a more pronounced hierarchical organization. Our results go beyond previous findings by indicating a transition to a healthier, more efficient, and flexible network architecture, with improved integration and segregation abilities in the brain of PwDS. Resting-state electrophysiological brain activity is used here for the first time to display meaningful relationships to underlying Down syndrome processes and outcomes of importance in a translational inquiry. This trial is registered with ClinicalTrials.gov Identifier NCT04390321.

TÍTULO / TITLE:   - Specialty clinics for adults with Down syndrome: A clinic survey.

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REVISTA / JOURNAL:    - Am J Med Genet A. 2021 Mar 17. doi: 10.1002/ajmg.a.62169.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.62169

AUTORES / AUTHORS: - Santoro S et al.

INSTITUCIÓN / INSTITUTION: - Division of Medical Genetics, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA. 

RESUMEN / SUMMARY: - Specialty centers improve care for patients with Down syndrome. The cohort of adults with Down syndrome is increasing, but the capacity for specialty centers to meet their medical care needs is unknown. Electronic survey of staff of specialty clinics for adults with Down syndrome was conducted. Review of online clinic listings, and calculation of the number of adults with Down syndrome were performed. Analysis identified the percent of adults with Down syndrome who could have their medical care needs met in a current specialty clinic. Fourteen specialty clinics report providing care for 4038 adults with Down syndrome. Respondents reported gaps in care including: limitations of existing clinics, need for additional clinics, and knowledgeable health professionals in Down syndrome. Survey-respondent clinic capacity would meet needs of 3% of adults with Down syndrome. Twenty-five clinics for adults with Down syndrome were listed online with capacity to care for 6517 adults with Down syndrome meeting the needs of 5% of the population. Additional clinic capacity is needed to meet the needs of adults with Down syndrome. Survey of existing clinics provides guidance to create additional clinics, including: must-have team members, current sources of clinic financial support, and gaps in current clinical care.

TÍTULO / TITLE:   - Piloting the use of global health measures in a Down syndrome clinic

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REVISTA / JOURNAL:    - J Appl Res Intellect Disabil. 2021 Mar 23. doi: 10.1111/jar.12866.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jar.12866

AUTORES / AUTHORS: - Santoro SL... Skotko B

INSTITUCIÓN / INSTITUTION: - Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA. 

RESUMEN / SUMMARY: - People with Down syndrome (DS) have a unique medical profile which may impact views of health. We aimed to explore the use of global health measures in DS. METHODS: Prospective survey in the Mass General Hospital Down Syndrome Program (MGH DSP) from December 2018 to July 2019 with Patient Reported Outcomes Measurement Information System (PROMIS)® instruments of global health. Analyses included use of scoring manuals, descriptive statistics and dependent samples t test. RESULTS: Seventeen adolescents, 48 adults with DS and 88 caregivers returned surveys; 137 were complete. Incomplete responses and notes showed limitations of the instruments in this population. Global health T-scores did not differ from the available comparative standardized scores to these measures from PROMIS® reference population (p > 0.05). CONCLUSIONS: In the MGH DSP, pilot global health instruments were completed by some adults with DS and caregivers, with some limitations and scores similar to the PROMIS® reference population.

TÍTULO / TITLE:   - “I had to think: This is not a child.” A qualitative exploration of how women/couples articulate their relation to the fetus/child following termination of a wanted pregnancy due to Down syndrome.

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REVISTA / JOURNAL:    - Sex Reprod Healthc. 2021 Feb 16;28:100606. doi: 10.1016/j.srhc.2021.100606.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.srhc.2021.100606

AUTORES / AUTHORS: - Lou S;et al.

INSTITUCIÓN / INSTITUTION: - DEFACTUM - Public Health & Health Services Research, Central Denmark Region, Aarhus, Denmark; Center for Fetal Diagnostics, Aarhus University Hospital, Aarhus, Denmark.  

RESUMEN / SUMMARY: - Termination of a wanted pregnancy due to fetal anomaly may generate complex feelings of grief and loss. The aim of this study was to explore the different ways that women/couples articulated their relation to the fetus/child following a termination of pregnancy due to a prenatal diagnosis of Down syndrome. METHOD: Qualitative interview study with 21 women/couples who had recently terminated a wanted pregnancy. Data were analyzed using thematic analysis. RESULTS: The analysis identified how some women detached themselves from the fetus/child following the diagnosis by mentally separating from the fetus/child, by acting as if they were not pregnant (e.g., by drinking wine), or by deliberately using the term ‘fetus’ to designate the fetus/child as a biological entity. The analysis also identified accounts of attachment such as singing a lullaby to the fetus/child or using the term ‘our child’ or ‘my baby’. However, accounts of detachment and attachment often intermingled and changed over time. Following the termination, many women/couples felt ambiguous about the sonogram as a symbol of the potential child. Overall, the analysis showed that the relation to and the meaning of the fetus/child was ambiguous and open to reinterpretation. CONCLUSION: The main contribution of this study is the identification of how articulations of attachment and detachment are not mutually exclusive but coexist and may change over time. Furthermore, we argue that detachment does not equal indifference. Thus, healthcare professionals must support the couple in finding a terminology and a narrative that are meaningful for them.

TÍTULO / TITLE:   - Quality of Life: Changes in Self-Perception in People with down Syndrome as a Result of Being Part of a Football/Soccer Team. Self-Reports and External Reports.

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REVISTA / JOURNAL:    - Brain Sci. 2021 Feb 12;11(2):226. doi: 10.3390/brainsci11020226.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/brainsci11020226

AUTORES / AUTHORS: - Camacho R;et al

INSTITUCIÓN / INSTITUTION: - Department of Cellular Biology, Physiology and Immunology, University of Cordoba, 14071 Cordoba, España. 

RESUMEN / SUMMARY: - The hypothesis posed was whether being part of a football/soccer team influenced the quality of life (QL) of the people who participated in it since their perception of themselves is enhanced by factors, such as self-determination, social inclusion, emotional well-being, physical well-being, material well-being, rights, personal development, and internal relationships. The objective was to evaluate the QL of people with Down Syndrome (DS) using their self-perception (n = 39) and the perception of the informants (family members, teachers) (n = 39). The KidsLife-Down Scale, with a few modifications, was used. In general, differences of opinion between the subgroups of participants with DS and informants showed that results were higher in terms of perception for participants in the DS subgroup. Scores for all variables were higher for those participants with DS who said they did engage in practicing competitive football/soccer. Although the perception of informants provides a great deal of information regarding the QL of participants with DS, participants with DS should also be involved in the evaluation process and their self-perceptions taken into account. It is not participating in a football team that causes the conclusions of the study, but training (which includes the friendly matches that are played), the cause correlated with the improvements detected in the athlete’s DS.

TÍTULO / TITLE:   - Ancient Romans and Down Syndrome.

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REVISTA / JOURNAL:    - Pediatr Res. 2021 Feb 2. doi: 10.1038/s41390-021-01366-0.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41390-021-01366-0

AUTORES / AUTHORS: - Vecchio D;et al Rare Diseases and Medical Genetics Unit, Academic Department of Pediatrics, Bambino Gesù Childrens Hospital, Rome, Italy

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: -

Respiratory - Respiratorio

TÍTULO / TITLE:   - Efficacy and adherence of noninvasive ventilation treatment in children with Down syndrome

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REVISTA / JOURNAL:    - Pediatr Pulmonol. 2021 Mar 17. doi: 10.1002/ppul.25308.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ppul.25308

AUTORES / AUTHORS: - MacDonagh L; Farrell L;et al.

INSTITUCIÓN / INSTITUTION: - Department of Respiratory, Children’s Health Ireland, Crumlin, Dublin, Ireland. 

RESUMEN / SUMMARY: - Objective: Children with Down syndrome (DS) have an increased prevalence of obstructive sleep apnea (OSA). Noninvasive ventilation (NIV) is a common modality of OSA treatment in this cohort. This study aimed to measure adherence and efficiency of NIV delivery in children with DS. Study design: This was a retrospective cohort study involving 106 children with confirmed OSA and home NIV with downloadable data capacity. Children were divided into DS (n = 44) and non-DS cohorts (n = 62). Adherence, clinical outcomes apnea-hypopnoea index (AHI), positive airway pressure delivery, and leakage were recorded and compared between DS and non-DS cohorts and within the DS cohort based on past surgical history. Results: Significantly greater NIV usage was observed in the DS cohort, they showed more consistent use with an increased percentage of days used relative to their non-DS counterparts (78.95 ± 2.26 vs. 72.11 ± 2.14, p = .031). However, despite greater usage, poorer clinical outcomes in the form of increased AHI (p = .0493) was observed in the DS cohort, where significantly greater leakage was also shown 41.00 ± 1.61 L/min versus 36.52 ± 1.18 L/min (p = .022). Twenty children with DS had prior cardiac surgery; compliance across all parameters was significantly reduced relative to those without. Conclusion: These data confirm that satisfactory NIV adherence is achievable in children with DS. However, we have identified excessive system leak at the machine-patient interface as a factor, which could undermine NIV efficacy in children with DS.

Therapeutics - Terapéutica

TÍTULO / TITLE:   - Treatment outcomes for infantile spasms in Japanese children with Down Syndrome.

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REVISTA / JOURNAL:    - Pediatr Int. 2021 Feb 26. doi: 10.1111/ped.14668.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/ped.14668

AUTORES / AUTHORS: - Nishimoto S;et al.

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki-city, Osaka, 569-8686, Japan. 

RESUMEN / SUMMARY: - To assess the treatment response to conventional antiepileptic drugs and low-dose ACTH therapy for infantile spasms in children with Down syndrome. METHODS: We retrospectively investigated the response and relapse rates, electroencephalography findings, patient characteristics during drug withdrawal, and developmental outcome in 10 children with Down syndrome treated for infantile spasms in our hospital. RESULTS: All patients showed cessation of infantile spasms and achieved electroencephalographic normalization. Spasm relapse occurred in one of 10 patients (10%). Antiepileptic drugs have been withdrawn for seven of 10 patients (70%), none of whom have experienced seizure relapse since drug withdrawal. The median developmental quotient (n=8) was 20.5, which shows that the developmental outcome was unfavorable. Low-dose ACTH therapy achieved a low seizure remission rate of 28.6%. CONCLUSIONS: Elucidation of the optimal treatment for infantile spasms in children with Down syndrome is needed to reduce the duration of infantile spasms and improve the developmental outcome.

TÍTULO / TITLE:   - Computerized physical and cognitive training improves the functional architecture of the brain in adults with Down syndrome: A network science EEG study.

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REVISTA / JOURNAL:    - Netw Neurosci. 2021 Mar 1;5(1):274-294. doi: 10.1162/netn_a_00177. eCollection 2021.

Enlace a la Editora de la Revista http://dx.doi.org/10.1162/netn_a_00177

AUTORES / AUTHORS: - Anagnostopoulou A;et al.

INSTITUCIÓN / INSTITUTION: - Medical Physics Laboratory, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece. 

RESUMEN / SUMMARY: - Understanding the neuroplastic capacity of people with Down syndrome (PwDS) can potentially reveal the causal relationship between aberrant brain organization and phenotypic characteristics. We used resting-state EEG recordings to identify how a neuroplasticity-triggering training protocol relates to changes in the functional connectivity of the brain’s intrinsic cortical networks. Brain activity of 12 PwDS before and after a 10-week protocol of combined physical and cognitive training was statistically compared to quantify changes in directed functional connectivity in conjunction with psychosomatometric assessments. PwDS showed increased connectivity within the left hemisphere and from left-to-right hemisphere, as well as increased physical and cognitive performance. Our findings reveal a strong adaptive neuroplastic reorganization as a result of the training that leads to a less-random network with a more pronounced hierarchical organization. Our results go beyond previous findings by indicating a transition to a healthier, more efficient, and flexible network architecture, with improved integration and segregation abilities in the brain of PwDS. Resting-state electrophysiological brain activity is used here for the first time to display meaningful relationships to underlying Down syndrome processes and outcomes of importance in a translational inquiry. This trial is registered with ClinicalTrials.gov Identifier NCT04390321.

TÍTULO / TITLE:   - Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome.

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REVISTA / JOURNAL:    - Sci Rep. 2021 Feb 25;11(1):4715. doi: 10.1038/s41598-021-83757-1.

Enlace a la Editora de la Revista http://dx.doi.org/10.1038/s41598-021-83757-1

AUTORES / AUTHORS: - Starbuck JM;et al.... Martnez-Abadas N;

INSTITUCIÓN / INSTITUTION: - GREAB-Research Group in Biological Anthropology, Department of Evolutionary Biology, Ecology and Environmental Sciences (BEECA), Universitat de Barcelona (UB), Barcelona, España.  

RESUMEN / SUMMARY: - Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical studi

TÍTULO / TITLE:   - From the lab to the people: major challenges in the biological treatment of Down syndrome.

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REVISTA / JOURNAL:    - AIMS Neurosci. 2021 Feb 9;8(2):284-294. doi: 10.3934/Neuroscience.2021015. eCollection 2021.

Enlace a la Editora de la Revista http://dx.doi.org/10.3934/Neuroscience.2021015

AUTORES / AUTHORS: - Rondal JA;

INSTITUCIÓN / INSTITUTION: - University of Liège, Belgium. 

RESUMEN / SUMMARY: - Down syndrome (DS) refers to a genetic condition due to the triplication of human chromosome 21. It is the most frequent autosomal trisomy. In recent years, experimental work has been conducted with the aim of removing or silencing the extra chromosome 21 (C21) in cells and normalizing genetic expression. This paper examines the feasibility of the move from laboratory studies to biologically treating “bone and flesh” people with DS. A chromosome or a gene therapy for humans is fraught with practical and ethical difficulties. To prevent DS completely, genome editing would have to be performed early on embryos in the womb. New in vitro findings point toward the possibility of epigenetic silencing the extra C21 in later embryonic or fetal life, or even postnatally for some aspects of neurogenesis. These possibilities are far beyond what is possible or allowed today. Another approach is through epigenetic regulation of the overexpression of particular genes in C21. Research with mouse modeling of DS is yielding promising results. Human applications have barely begun and are questioned on ethical grounds.

Education - Educación

TÍTULO / TITLE:   - Evaluating working memory outcome measures for children with Down syndrome.

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REVISTA / JOURNAL:    - J Intellect Disabil Res. 2021 Mar 25. doi: 10.1111/jir.12833.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jir.12833

AUTORES / AUTHORS: - Schworer EK et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA. 

RESUMEN / SUMMARY: - There is a critical need for the psychometric evaluation of outcome measures to be used in clinical trials targeting cognition in Down syndrome (DS). This study examines a specific cognitive skill that is of particular importance in DS, working memory, and the psychometric properties of a set of standardised measurements to assess working memory in individuals with DS. METHODS: Ninety children and adolescents ages 6 to 18 years old with DS were assessed on a selection of verbal and visuospatial working memory subtests of standardised clinical assessments at two time points to examine feasibility, distributional qualities, test-retest reliability and convergent validity against a priori criteria. Caregivers also completed an adaptive behaviour questionnaire to address working memory subtests’ associations with broader developmental functioning. RESULTS: The Stanford Binet-5 Verbal Working Memory, Differential Ability Scales-2 Recognition of Pictures, Stanford Binet-5 Nonverbal Working Memory and Wechsler Intelligence Scale for Children-5 Picture Span measures met the most psychometric criteria overall across the full age and IQ range of the study. Although Differential Ability Scales-2 Recall of Sequential Order and Differential Ability Scales-2 Recall of Digits Backward met the fewest a priori criteria, follow-up analyses suggested greater feasibility in specific age and IQ ranges. CONCLUSIONS: Several working memory measures appear to be psychometrically sound and appropriate for use in clinical trials for children with DS, especially when focusing on raw scores. However, floor effects on standard scores and feasibility of some measures were problematic. Guidelines for use of the working memory subtests with this population are provided.

TÍTULO / TITLE:   - Feasibility of a syndrome-informed micro-intervention for infants with Down syndrome.

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REVISTA / JOURNAL:    - J Intellect Disabil Res. 2021 Apr;65(4):320-339. doi: 10.1111/jir.12814. Epub 2021 Jan 31.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jir.12814

AUTORES / AUTHORS: - Fidler DJ ... Daunhauer LA;

INSTITUCIÓN / INSTITUTION: - Human Development and Family Studies, Colorado State University, Fort Collins, CO, USA. 

RESUMEN / SUMMARY: - Infants with Down syndrome (DS) are at risk for a range of phenotypic outcomes, including delays in the onset of reaching behaviour, a critical skill that facilitates early learning. This parallel-group feasibility and pilot study presents findings from a parent-mediated micro-intervention that aimed to support the development of reaching behaviour in a sample of infants with DS. METHODS: Participants were 73 infants with DS and their caregivers. Infants who qualified for the home-based intervention (based on manual skill performance on Bayley Scales of Infant and Toddler Development, Third Edition items) were randomly assigned individually or by geographical region to a treatment or an alternative treatment condition that involved toy-based interactions with caregivers. Infants in the treatment condition experienced facilitated reaching during the toy-based interactions through the use of Velcro-affixed mittens and toys. RESULTS: Forty-two infants met criteria to participate in the intervention, and 37 participated in both baseline and post-treatment visits. At post-treatment, infants in the treatment condition demonstrated shorter latencies to make contact with objects and showed higher frequencies of reach attempts and swats at objects than infants in the alternative treatment group. These findings were more pronounced when examining a chronological age-restricted subgroup of infants 5 to 10 months. CONCLUSIONS: Findings suggest that a syndrome-informed approach to targeted intervention may be a promising application of phenotyping science in DS and other neurogenetic conditions associated with intellectual disability.

TÍTULO / TITLE:   - Sexual behaviours and education in adolescents and young adults with Down syndrome: A grounded theory study of experiences and opinions of their mothers in Turkey.

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REVISTA / JOURNAL:    - Res Dev Disabil. 2021 May;112:103907. doi: 10.1016/j.ridd.2021.103907. Epub 2021 Feb 26.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ridd.2021.103907

AUTORES / AUTHORS: - Gokgoz C;... Kabukcuoglu K;

INSTITUCIÓN / INSTITUTION: - Akdeniz University, Faculty of Nursing, Department of Obstetrics & Gynaecological Nursing, Antalya, Turkey.  

RESUMEN / SUMMARY: - This study aimed to gain a deeper understanding of the experiences and opinions of mothers about sexual behaviours and sexual education of their children with DS who are AYAs in Turkey. The study utilised a classic grounded theory approach. In-depth interviews were conducted with 12 mothers. Data were analyzed by the constant comparative method. Mothers expressed that they could not address the sexual needs of their child because they did not feel they could provide sufficient care to their child. Mothers used pressure and control tactics and neglect of the sexuality to cope with their children’s sexuality. Mothers described their meaning of the sexuality, fear of stigmatization and gender issues as determinant factors on the dealing with the sexuality. They stated their knowledge about sexuality is not enough to provide sexual education. Many cultural issues such as gender, meaning of the sexuality and burden of care was described as determinant factors and difficulties to providing sexual education. Therefore, educational and supportive programmes for parents should be conducted. Comprehensive, valid and individualized sexual education program also should be provided AYAs with DS.

TÍTULO / TITLE:   - Infant precursors of executive function in Down syndrome.

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REVISTA / JOURNAL:    - J Intellect Disabil Res. 2021 Mar 2. doi: 10.1111/jir.12824.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jir.12824

AUTORES / AUTHORS: - Schworer EK ... Daunhauer LA;

INSTITUCIÓN / INSTITUTION: - Human Development and Family Studies, Colorado State University, Fort Collins, CO, USA. 

RESUMEN / SUMMARY: - Although early features of infant cognition are predictive of executive function (EF) in typically developing (TD) children, there is little information regarding the developmental origins of EF in neurogenetic conditions, such as Down syndrome (DS). METHODS: The current study compared the performance of infants with and without DS on three dimensions that are hypothesised EF precursors: visual engagement, attention shifting and action planning. Additionally, the relationship between these EF precursors at Time 1 and EF performance at Time 2 (6 months later) was examined in the DS group. Participants were 36 infants with DS, M chronological = 12.65 months, SD = 2.11; M developmental age = 8.84 months, SD = 2.22, and 36 TD infants, M chronological age = 8.62, SD = 3.06; M developmental age = 8.64 months, SD = 3.40. RESULTS: Infants with DS visually engaged with objects for longer durations and demonstrated challenges with action planning compared with TD infants at Time 1. Attention shifting at Time 1 significantly predicted EF performance at Time 2 in the DS group. CONCLUSIONS: This study provides evidence that an early atypical presentation of EF precursors is detectable during infancy in DS and is predictive of subsequent EF performance. These findings contribute to the identification of areas of early cognitive risk in DS and can inform future interventions in this population.

TÍTULO / TITLE:   - Parent-based training of basic number skills in children with Down syndrome using an adaptive computer game.

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REVISTA / JOURNAL:    - Res Dev Disabil. 2021 May;112:103919. doi: 10.1016/j.ridd.2021.103919. Epub 2021 Mar 6.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ridd.2021.103919

AUTORES / AUTHORS: - Lanfranchi S;

INSTITUCIÓN / INSTITUTION: - University of Padova, Italy.  

RESUMEN / SUMMARY: - Numeracy is an area of difficulty for children with Down syndrome (DS). It has been demonstrated that The Number Race, a non-commercial adaptive computer game designed to foster basic mathematical abilities, represents a promising instrument to enhance these skills in children with DS when delivered by an expert in a clinical setting. AIMS: In the present study, we assessed the efficacy of The Number Race when administered at home by properly instructed and remotely supervised parents. METHODS AND PROCEDURES: Basic numerical skills were assessed before and after training, as well as at three-months follow-up. Performance of children with DS who worked at home with the parent (PG) was compared with that of children who received the training by an expert (EG). For both groups, the training lasted ten weeks, with two weekly sessions of 20-30 min. OUTCOMES AND RESULTS: Results show that both groups improved across various measures of numerical proficiency, including the overall score of the numeracy assessment battery, while only the EG showed an improvement in a measure of mental calculation. The improvements were maintained three months after the end of the training. CONCLUSIONS AND IMPLICATIONS: These findings confirm the efficacy of The Number Race and extend it to an home-based setting, whereby parents administer the training with external supervision.

TÍTULO / TITLE:   - Intelligibility in Down syndrome: Effect of measurement method and listener experience.

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REVISTA / JOURNAL:    - Int J Lang Commun Disord. 2021 Mar 30. doi: 10.1111/1460-6984.12602.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/1460-6984.12602

AUTORES / AUTHORS: - OLeary D... Gibbon F;

INSTITUCIÓN / INSTITUTION: - Department of Speech and Hearing Sciences, Brookfield Complex, University College Cork, Cork, Ireland. 

RESUMEN / SUMMARY: - Speech intelligibility is a global indicator of the severity of a speech problem. It is a measure that has been used frequently in research and clinical assessment of speech. Previous studies have shown that factors, such as measurement method and listener experience, can influence speech intelligibility scores. However, these factors of speech intelligibility assessment have not yet been investigated in people with Down syndrome (DS). AIMS: To compare the speech intelligibility scores in speakers with DS measured using two methods: orthographic transcription and visual analogue scale (VAS), by two groups of listeners, experienced listeners and naive listeners. Also, to examine the relationship across the four sets of speech intelligibility scores by means of correlational analysis. METHODS & PROCEDURES: A total of 30 adolescents and adults with DS read or repeated 12 sentences from a standardized test of intelligibility for adults with dysarthria. Each sentence was saved as a separate sound file and the 360 sentences were divided to form eight sets of stimuli. A total of 32 adults (16 experienced and 16 naive) served as listeners of speech intelligibility. Each listener heard a single set of sentences and independently estimated the level of intelligibility for each sentence using a VAS in one task and wrote down the words perceived (i.e., orthographic transcription) in another task. The order of the two tasks was counterbalanced across listeners and the tasks were completed at least 1 week apart. OUTCOMES & RESULTS: Repeated-measures analysis of variance (ANOVA), confirmed by mixed-methods analysis, showed that the scores obtained using orthographic transcription were significantly higher than those obtained using VAS; and the experienced listeners’ scores were significantly higher than the naive listeners’ scores. Spearman rank correlation analysis showed that the four sets of scores across all conditions were strongly positively correlated with each other. CONCL

TÍTULO / TITLE:   - Exploring Expressive Communication Skills in a Cross-Sectional Sample of Individuals With a Dual Diagnosis of Autism Spectrum Disorder and Down Syndrome.

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REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2021 Mar 1;126(2):97-113. doi: 10.1352/1944-7558-126.2.97.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-126.2.97

AUTORES / AUTHORS: - Cook A;et al.

INSTITUCIÓN / INSTITUTION: - Alexandria Cook, Emily D. Quinn, and Charity Rowland, Oregon Health and Science University, Institute on Development and Disability, Portland. 

RESUMEN / SUMMARY: - Individuals with a comorbid diagnosis of Down syndrome (DS) and autism spectrum disorder (ASD) have been found to exhibit greater deficits in expressive communication than individuals with DS only. We hypothesized that individuals with a comorbid diagnosis (n = 430) would have significantly lower Communication Matrix scores and specifically social communication scores than individuals with DS alone (n = 4,352). In a sample of 4,782 individuals with DS, scores for individuals with a comorbid diagnosis were on average 18.01 points and 7.26 points lower for total score and social score respectively as compared to individuals with DS. Comorbid diagnosis accounted for 10.5% of the variance in communication scores. Between-group differences in referential gestures and symbolic communication behaviors were also observed.

TÍTULO / TITLE:   - Early Regulatory Skills and Social Communication Development in Infants with Down Syndrome.

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REVISTA / JOURNAL:    - Brain Sci. 2021 Feb 9;11(2):208. doi: 10.3390/brainsci11020208.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/brainsci11020208

AUTORES / AUTHORS: - Schworer EK; et al.

INSTITUCIÓN / INSTITUTION: - Division of Developmental and Behavioral Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA. 

RESUMEN / SUMMARY: - Children with Down syndrome (DS) demonstrate substantial variability in communication and language outcomes. One potential source of variability in this skill area may be early regulatory function. Characterizing the early link between regulatory function and early social communication may benefit infants with DS at risk of difficulties with social communication and language skill acquisition. Forty-three infants with DS were assessed at two time points, six months apart. At Time 1, the average chronological age was 9.0 months (SD = 3.9) and caregivers completed the Infant Behavior Questionnaire-Revised (IBQ-R) to assess regulatory function. Six months later, caregivers rated infant communication at the second visit using the Communication and Symbolic Behavior Scales Infant Toddler Checklist (CSBS-ITC). Infant developmental level was assessed at both visits using the Bayley Scales of Infant and Toddler Development, Third Edition and caregivers reported on developmental history and biomedical comorbidities. Infant regulatory function at Time 1 predicted social communication outcomes at Time 2, six months later. Findings from this study suggest that elevated risk for pronounced communication challenges may be detectable as early as infancy in DS.

TÍTULO / TITLE:   - Analysing Touchscreen Gestures: A Study Based on Individuals with Down Syndrome Centred on Design for All.

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REVISTA / JOURNAL:    - Sensors (Basel). 2021 Feb 13;21(4):1328. doi: 10.3390/s21041328.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/s21041328

AUTORES / AUTHORS: - Martin-Gutierrez J; Del Rio Guerra MS

INSTITUCIÓN / INSTITUTION: - Department of Techniques and Projects in Engineering and Architecture, Universidad de La Laguna, Av. Angel Guimerá sn, 38071 Tenerife, Spain. 

RESUMEN / SUMMARY: - There has been a conscious shift towards developing increasingly inclusive applications. However, despite this fact, most research has focused on supporting those with visual or hearing impairments and less attention has been paid to cognitive impairments. The purpose of this study is to analyse touch gestures used for touchscreens and identify which gestures are suitable for individuals living with Down syndrome (DS) or other forms of physical or cognitive impairments. With this information, app developers can satisfy Design for All (DfA) requirements by selecting adequate gestures from existing lists of gesture sets. Twenty touch gestures were defined for this study and a sample group containing eighteen individuals with Down syndrome was used. A tool was developed to measure the performance of touch gestures and participants were asked to perform simple tasks that involved the repeated use of these twenty gestures. Three variables are analysed to establish whether they influence the success rates or completion times of gestures, as they could have a collateral effect on the skill with which gestures are performed. These variables are Gender, Type of Down syndrome, and Socioeconomic Status. Analysis reveals that significant difference is present when a pairwise comparison is performed, meaning individuals with DS cannot perform all gestures with the same ease. The variables Gender and Socioeconomic Status do not influence success rates or completion times, but Type of DS does.

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