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AGING - ENVEJECIMIENTO

TÍTULO / TITLE:    - Normalizing the gene dosage of Dyrk1A in a mouse model of Down syndrome rescues several Alzheimer’s disease phenotypes

REVISTA / JOURNAL:    - Neurobiol Dis. 2017 Jun 21;106:76-88. doi: 10.1016/j.nbd.2017.06.010

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.nbd.2017.06.010

AUTORES / AUTHORS: - Garcia-Cerro S; Rueda N; Vidal V; Lantigua S; Martinez-Cue C

INSTITUCIÓN / INSTITUTION: - Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Santander, España   martinec@unican.es

RESUMEN / SUMMARY: - The intellectual disability that characterizes Down syndrome (DS) is primarily caused by prenatal changes in central nervous system growth and differentiation. However, in later life stages, the cognitive abilities of DS individuals progressively decline due to accelerated aging and the development of Alzheimer’s disease (AD) neuropathology. The AD neuropathology in DS has been related to the overexpression of several genes encoded by Hsa21 including DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), which encodes a protein kinase that performs crucial functions in the regulation of multiple signaling pathways that contribute to normal brain development and adult brain physiology. Studies performed in vitro and in vivo in animal models overexpressing this gene have demonstrated that the DYRK1A gene also plays a crucial role in several neurodegenerative processes found in DS. The Ts65Dn (TS) mouse bears a partial triplication of several Hsa21 orthologous genes, including Dyrk1A, and replicates many DS-like abnormalities, including age-dependent cognitive decline, cholinergic neuron degeneration, increased levels of APP and Abeta, and tau hyperphosphorylation. To use a more direct approach to evaluate the role of the gene dosage of Dyrk1A on the neurodegenerative profile of this model, TS mice were crossed with Dyrk1A KO mice to obtain mice with a triplication of a segment of Mmu16 that includes this gene, mice that are trisomic for the same genes but only carry two copies of Dyrk1A, euploid mice with a normal Dyrk1A dosage, and CO animals with a single copy of Dyrk1A. Normalizing the gene dosage of Dyrk1A in the TS mouse rescued the density of senescent cells in the cingulate cortex, hippocampus and septum, prevented cholinergic neuron degeneration, and reduced App expression in the hippocampus, Abeta load in the cortex and hippocampus, the expression of phosphorylated tau at the Ser202 residue in the hippocampus and cerebellum and the levels

TÍTULO / TITLE:    - A Review of Biomarkers for Alzheimer’s Disease in Down Syndrome.

REVISTA / JOURNAL:    - Neurol Ther. 2017 Jul;6(Suppl 1):69-81. doi: 10.1007/s40120-017-0071-y. Epub 2017 Jul 21.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s40120-017-0071-y

AUTORES / AUTHORS: - Lee NC; et al; Chien YH; Hwu WL;

INSTITUCIÓN / INSTITUTION: - Department of Medical Genetics and Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.   ncleentu@ntu.edu.tw

RESUMEN / SUMMARY: - Down syndrome (Trisomy 21; DS) is a unique disease known to be associated with early-onset Alzheimer’s disease (AD). The initial presentation of AD in DS is usually difficult to recognize, owing to the underlying intellectual disabilities. Using biomarkers as a prediction tool for detecting AD in at-risk people with DS may benefit patient care. The objective of this review is to discuss the utility of biomarkers in DS on the basis of the pathophysiology of the disease and to provide an update on recent studies in this field. Only through the comprehensive assessment of clinical symptoms, imaging studies, and biomarker analyses can people with DS who are at risk for AD be diagnosed early. Studies for biomarkers of AD in DS have focused on the common pathophysiology of AD in people with DS and in the general population. The most extensively studied biomarkers are amyloid and tau. Owing to the nature of amyloid precursor protein overproduction in DS, the baseline beta-amyloid (Abeta) plasma levels are higher than those in controls. Hence, the changes in Abeta are considered to be a predictive marker for AD in DS. In addition, other markers related to telomere length, neuroinflammation, and methylation have been investigated for their correlation with AD progression. Future studies including different ethnic groups may be helpful to collect sufficient data to monitor drug safety and efficacy, stratify patients at risk for AD, and quantify the benefit of treatment.

TÍTULO / TITLE:    - Elucidating Pathogenic Mechanisms of Early-onset Alzheimer’s Disease in Down Syndrome Patients.

REVISTA / JOURNAL:    - Yakugaku Zasshi. 2017;137(7):801-805. doi: 10.1248/yakushi.16-00236-2.

Enlace a la Editora de la Revista 1248/yakushi.16-00236-2

AUTORES / AUTHORS: - Asai M; et al

INSTITUCIÓN / INSTITUTION: - Department of Genome-based Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University  

RESUMEN / SUMMARY: - Down syndrome (DS) patients demonstrate the neuropathology of Alzheimer’s disease (AD) characterized by the formation of senile plaques and neurofibrillary tangles by age 40-50 years. It has been considered for a number of years that 1.5-fold expression of the gene for the amyloid precursor protein (APP) located on chromosome 21 leading to overproduction of amyloid-beta peptide (Abeta) results in the early onset of AD in adults with DS. However, the mean age of onset of familial AD with the Swedish mutation on APP which has high affinity for beta-secretase associated with a dramatic increase in Abeta production is about 55 years. This paradox indicates that there is a poor correlation between average ages of AD onset and the theoretical amount of Abeta production and that there are factors exacerbating AD on chromosome 21. We therefore focused on dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), since overexpressing transgenic mice show AD-like brain pathology. The overexpression of DYRK1A caused suppression of the activity of neprilysin (NEP), which is a major Abeta-degrading enzyme in the brain, and phosphorylation at the NEP cytoplasmic domain. NEP activity was markedly reduced in fibroblasts derived from DS patients compared with that in fibroblasts derived from healthy controls. This impaired activity of NEP was rescued by DYRK1A inhibition. These results show that DYRK1A overexpression causes suppression of NEP activity through its phosphorylation in DS patients. Our results suggest that DYRK1A inhibitors could be effective against AD not only in adults with DS but also in sporadic AD patients.

TÍTULO / TITLE:    - Age exacerbates abnormal protein expression in a mouse model of Down syndrome.

REVISTA / JOURNAL:    - Neurobiol Aging. 2017 Sep;57:120-132. doi: 10.1016/j.neurobiolaging.2017.05.002. Epub 2017 May 10.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.neurobiolaging.2017.05.002

AUTORES / AUTHORS: - Ahmed MM; Gardiner KJ et al

INSTITUCIÓN / INSTITUTION: - Linda Crnic Institute for Down Syndrome, Aurora, CO, USA; Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, CO, USA; Human Medical Genetics and Genomics, and Neuroscience Programs, University of Colorado De   Katheleen.gardiner@ucdenver.edu

RESUMEN / SUMMARY: - The Ts65Dn is a popular mouse model of Down syndrome (DS). It displays DS-relevant features of learning/memory deficits and age-related loss of functional markers in basal forebrain cholinergic neurons. Here we describe protein expression abnormalities in brain regions of 12-month-old male Ts65Dn mice. We show that the magnitudes of abnormalities of human chromosome 21 and non-human chromosome 21 orthologous proteins are greater at 12 months than at approximately 6 months. Age-related exacerbations involve the number of components affected in the mechanistic target of rapamycin pathway, the levels of components of the mitogen-activated protein kinase pathway, and proteins associated with Alzheimer’s disease. Among brain regions, the number of abnormalities in cerebellum decreased while the number in cortex greatly increased with age. The Ts65Dn is being used in preclinical evaluations of drugs for cognition in DS. Most commonly, drug evaluations are tested in approximately 4- to 6-month-old mice. Data on age-related changes in magnitude and specificity of protein perturbations can be used to understand the molecular basis of changes in cognitive ability and to predict potential age-related specificities in drug efficacies.

TÍTULO / TITLE:    - Cognitive decline and brain amyloid-beta accumulation across 3 years in adults with Down syndrome.

REVISTA / JOURNAL:    - Neurobiol Aging. 2017 Jun 2;58:68-76. doi: 10.1016/j.neurobiolaging.2017.05.019.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.neurobiolaging.2017.05.019

AUTORES / AUTHORS: - Hartley SL; et al.

INSTITUCIÓN / INSTITUTION: - Department of Human Development & Family Studies, University of Wisconsin, Madison, WI, USA; University of Wisconsin-Madison, Waisman Center, Madison, WI, USA.   slhartley@wisc.edu

RESUMEN / SUMMARY: - Adults with Down syndrome (DS) have a high incidence of Alzheimer’s disease (AD), providing a unique opportunity to explore the early, preclinical stages of AD neuropathology. We examined change in brain amyloid-beta accumulation via the positron emission tomography tracer [11C] Pittsburgh compound B (PiB) across 2 data collection cycles, spaced 3 years apart, and decline in cognitive functioning in 58 adults with DS without clinical AD. PiB retention increased in the anterior cingulate gyrus, precuneus cortex, parietal cortex, and anterior ventral striatum. Across the 2 cycles, 14 (27.5%) participants were consistently PiB+, 31 (60.8%) were consistently PiB-, and 6 (11.7%) converted from PiB- at cycle 1 to PiB+ at cycle 2. Increased global amyloid-beta was related to decline in verbal episodic memory, visual episodic memory, executive functioning, and fine motor processing speed. Participants who were consistently PiB+ demonstrated worsening of episodic memory, whereas participants who were consistently PiB- evidenced stable or improved performance. Amyloid-beta accumulation may be a contributor to or biomarker of declining cognitive functioning in preclinical AD in DS.

TÍTULO / TITLE:    - Aging rather than aneuploidy affects monoamine neurotransmitters in brain regions of Down syndrome mouse models.

REVISTA / JOURNAL:    - Neurobiol Dis. 2017 Sep;105:235-244. doi: 10.1016/j.nbd.2017.06.007. Epub 2017 Jun 15.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.nbd.2017.06.007

AUTORES / AUTHORS: - Dekker AD; De Deyn PP; et al.

INSTITUCIÓN / INSTITUTION: - Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Univers   p.p.de.deyn@umcg.nl

RESUMEN / SUMMARY: - Altered concentrations of monoamine neurotransmitters and metabolites have been repeatedly found in people with Down syndrome (DS, trisomy 21). Because of the limited availability of human post-mortem tissue, DS mouse models are of great interest to study these changes and the underlying neurobiological mechanisms. Although previous studies have shown the potential of Ts65Dn mice - the most widely used mouse model of DS - to model noradrenergic changes, a comprehensive monoaminergic characterization in multiple brain regions has not been performed so far. Here, we used RP-HPLC with electrochemical detection to quantify (nor)adrenergic (NA, adrenaline and MHPG), dopaminergic (DA, HVA and DOPAC), and serotonergic compounds (tryptophan, 5-HT and 5-HIAA) in ten regionally dissected brain regions of Ts65Dn mice, as well as in Dp1Tyb mice - a novel DS mouse model. Comparing young adult aneuploid mice (2.5-5.5months) with their euploid WT littermates did not reveal generalized monoaminergic dysregulation, indicating that the genetic overload in these mice barely affected the absolute concentrations at this age. Moreover, we studied the effect of aging in Ts65Dn mice: comparing aged animals (12-13months) with their younger counterparts revealed a large number of significant changes. In general, the (nor)adrenergic system appeared to be reduced, while serotonergic compounds were increased with aging. Dopaminergic alterations were less consistent. These overall patterns appeared to be relatively similar for Ts65Dn and WT mice, though more observed changes were regarded significant for WT mice. Similar human post-mortem studies are necessary to validate the monoaminergic construct validity of the Ts65Dn and Dp1Typ mouse models.

TÍTULO / TITLE:    - A prospective 20-year longitudinal follow-up of dementia in persons with Down syndrome.

REVISTA / JOURNAL:    - J Intellect Disabil Res. 2017 Jun 29. doi: 10.1111/jir.12390.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jir.12390

AUTORES / AUTHORS: - McCarron M; et al.

INSTITUCIÓN / INSTITUTION: - School of Nursing and Midwifery, Trinity College Dublin, Dublin, Ireland.  

RESUMEN / SUMMARY: - GOAL: To examine dementia characteristics, age at onset and associated co-morbidities in persons with Down syndrome. METHOD: A total of 77 people with Down syndrome aged 35 years and older were followed up from 1996 to 2015. The diagnosis of dementia was established using the modified ICD 10 Criteria and a combination of objective and informant-based tests. Cognitive tests included the Test for Severe Impairment and the Down Syndrome Mental Status Examination; adaptive behaviour was measured using the Daily Living Skills Questionnaire, and data from the Dementia Questionnaire for People with Intellectual Disabilities have been available since 2005. RESULTS: Over the 20-year period, 97.4% (75 of 77) persons developed dementia with a mean age of dementia diagnosis of 55 years (SD = 7.1, median = 56 years). Clinical dementia was associated with cognitive and function decline and seizure activity. Risk for dementia increased from 23% in those aged 50 years to 80% in those aged 65 years and above. There were no differences by level of ID. CONCLUSION: The previously reported high risk levels for dementia among people with Down syndrome were confirmed in this data as was the relationship with late onset epilepsy. The value of the instruments utilised in tracking decline and helping to confirm diagnosis is further highlighted.

TÍTULO / TITLE:    - Dissociation of Down syndrome and Alzheimer’s disease effects with imaging.

REVISTA / JOURNAL:    - Alzheimers Dement (N Y). 2016 Jun;2(2):69-81. doi: 10.1016/j.trci.2016.02.004.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.trci.2016.02.004

AUTORES / AUTHORS: - Matthews DC; Rafii MS; et al

INSTITUCIÓN / INSTITUTION: - Alzheimer’s Disease Cooperative Study, Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, CA, USA.  

RESUMEN / SUMMARY: - INTRODUCTION: Down Syndrome (DS) adults experience accumulation of Alzheimer’s disease (AD)-like amyloid plaques and tangles and a high incidence of dementia and could provide an enriched population to study AD-targeted treatments. However, to evaluate effects of therapeutic intervention, it is necessary to dissociate the contributions of DS and AD from overall phenotype. Imaging biomarkers offer the potential to characterize and stratify patients who will worsen clinically but have yielded mixed findings in DS subjects. METHODS: We evaluated 18F fluorodeoxyglucose positron emission tomography (PET), florbetapir PET, and structural magnetic resonance (sMR) image data from 12 nondemented DS adults using advanced multivariate machine learning methods. RESULTS: Our results showed distinctive patterns of glucose metabolism and brain volume enabling dissociation of DS and AD effects. AD-like pattern expression corresponded to amyloid burden and clinical measures. DISCUSSION: These findings lay groundwork to enable AD clinical trials with characterization and disease-specific tracking of DS adults.

TÍTULO / TITLE:    - Microvascular changes in Down syndrome with Alzheimer-type pathology: Insights into a potential vascular mechanism for Down syndrome and Alzheimer’s disease.

REVISTA / JOURNAL:    - Alzheimers Dement. 2017 Jun 13. pii: S1552-5260(17)30219-4. doi:

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jalz.2017.05.003

AUTORES / AUTHORS: - Drachman DA, Smith TW; et al

INSTITUCIÓN / INSTITUTION: - Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA; Department of Pathology, University of Massachusetts Medical School, USA.   thomas.smith@umassmemorial.org

RESUMEN / SUMMARY: - INTRODUCTION: The mechanism triggering degeneration in Alzheimer’s disease (AD) remains uncertain. Therapeutic failure following amyloid beta (Abeta) removal casts doubt on amyloid neurotoxicity per se as the primary cause of AD. Impaired microvascular function has been suggested as an alternative etiology. People with Down syndrome (DS) develop Alzheimer pathology, but whether microvascular impairment also occurs in DS (as in AD) is unknown. METHODS: We examined brain microvasculature in five DS subjects with AD-type histopathology, seven AD cases, and seven controls without AD-type pathology. We counted microvessels in five anatomic regions and assessed endothelial integrity by CD31 immunohistochemistry. RESULTS: Microvascular numbers and endothelial integrity were significantly diminished in DS brains compared with controls and were similar to AD brains. DISCUSSION: People with DS and trisomy 21 produce a large amount of Abeta. If Alzheimer pathology occurred in DS without microvascular loss or endothelial impairment, a direct neurotoxic Abeta mechanism would be supported and microvascular impairment rejected. The observation of microvascular impairment in DS with Alzheimer changes fails to reject the microvascular hypothesis and provides some support for this potential mechanism of injury.

TÍTULO / TITLE:    - Early increased density of cyclooxygenase-2 (COX-2) immunoreactive neurons in Down syndrome.

REVISTA / JOURNAL:    - Folia Neuropathol. 2017;55(2):154-160. doi: 10.5114/fn.2017.68582.

Enlace a la Editora de la Revista http://dx.doi.org/10.5114/fn.2017.68582

AUTORES / AUTHORS: - Mulet M et al

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Neuroinflammation is one of the hallmarks of Alzheimer’s disease. One of the enzymes involved in neuroinflammation, even in early stages of the disease, is COX-2, an inducible cyclooxygenase responsible for the generation of eicosanoids and for the generation of free radicals. Individuals with Down syndrome develop Alzheimer’s disease early in life. Previous studies pointed to the possible overexpression of COX-2 and correlated it to brain regions affected by the disease. We analysed the COX-2 expression levels in individuals with Down syndrome and in young, adult and old mice of the Ts65Dn mouse model for Down syndrome. We have observed an overexpression of COX-2 in both, Down syndrome individuals and mice. Importantly, mice already presented an overexpression of COX-2 at postnatal day 30, before neurodegeneration begins; which suggests that neuroinflammation may underlie the posterior neurodegeneration observed in individuals with Down syndrome and in Ts65Dn mice and could be a factor for the premature appearance of Alzheimer’s disease

TÍTULO / TITLE:    - Longitudinal changes in amyloid positron emission tomography and volumetric magnetic resonance imaging in the nondemented Down syndrome population.

REVISTA / JOURNAL:    - Alzheimers Dement (Amst). 2017 May 23;9:1-9. doi: 10.1016/j.dadm.2017.05.001. eCollection 2017.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.dadm.2017.05.001

AUTORES / AUTHORS: - Lao PJ; et al

INSTITUCIÓN / INSTITUTION: - University of Wisconsin-Madison, Madison, WI, USA.  

RESUMEN / SUMMARY: - INTRODUCTION: Down syndrome (DS) arises from a triplication of chromosome 21, causing overproduction of the amyloid precursor protein and predisposes individuals to early Alzheimer’s disease (AD). METHODS: Fifty-two nondemented adults with DS underwent two cycles of carbon 11-labeled Pittsburgh compound B ([11C]PiB) and T1 weighted magnetic resonance imaging (MRI) scans 3.0 +/- 0.6 years apart. Standard uptake value ratio (SUVR) images (50-70 minutes; cerebellar gray matter [GM]) and GM volumes were analyzed in standardized space (Montreal Neurological Institute space). RESULTS: 85% of PiB(-) subjects remained PiB(-), whereas 15% converted to PiB(+), predominantly in the striatum. None reverted from PiB(+) to PiB(-). Increases in SUVR were distributed globally, but there were no decreases in GM volume. The PiB positivity groups differed in the percent rate of change in SUVR [PiB(-): 0.5%/year, PiB converters: 4.9%/year, and PiB(+): 3.7%/year], but not in GM volume. DISCUSSION: Despite the characteristic striatum-first pattern, the global rate of amyloid accumulation differs by pre-existing amyloid burden and precedes atrophy or dementia in the DS population, similar to general AD progression.

TÍTULO / TITLE:    - Disturbance of redox homeostasis in Down Syndrome: Role of iron dysmetabolism.

REVISTA / JOURNAL:    - Free Radic Biol Med. 2017 Jul 10. pii: S0891-5849(17)30681-0. doi: 10.1016/j.freeradbiomed.2017.07.0

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.freeradbiomed.2017.07.009

AUTORES / AUTHORS: - Barone E; Perluigi M; et al

INSTITUCIÓN / INSTITUTION: - Department of Biochemical Sciences, Sapienza University of Rome, P.le Aldo Moro, 5, 00185 Rome, Italy.   marzia.perluigi@uniroma1.it

RESUMEN / SUMMARY: - Down Syndrome (DS) is the most common genetic form of intellectual disability that leads in the majority of cases to development of early-onset Alzheimer-like dementia (AD). The neuropathology of DS has several common features with AD including alteration of redox homeostasis, mitochondrial deficits, and inflammation among others. Interestingly, some of the genes encoded by chromosome 21 are responsible of increased oxidative stress (OS) conditions that are further exacerbated by decreased antioxidant defense. Previous studies from our groups showed that accumulation of oxidative damage is an early event in DS neurodegeneration and that oxidative modifications of selected proteins affects the integrity of the protein degradative systems, antioxidant response, neuronal integrity and energy metabolism. In particular, the current review elaborates recent findings demonstrating the accumulation of oxidative damage in DS and we focus attention on specific deregulation of iron metabolism, which affects both the central nervous system and the periphery. Iron dysmetabolism is a well-recognized factor that contributes to neurodegeneration; thus we opine that better understanding how and to what extent the concerted loss of iron dyshomeostasis and increased OS occur in DS could provide novel insights for the development of therapeutic strategies for the treatment of Alzheimer-like dementia.

CARDIOLOGY - CARDIOLOGÍA

TÍTULO / TITLE:    - Congenital heart disease and cardiac procedural outcomes in patients with trisomy 21 and Turner syndrome.

REVISTA / JOURNAL:    - Congenit Heart Dis. 2017 Jul 24. doi: 10.1111/chd.12521.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/chd.12521

AUTORES / AUTHORS: - Morales-Demori R

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Congenital heart disease (CHD) is present in approximately 50% of patients with trisomy 21 (T21) and Turner syndrome (TS). According to the American Academy of Pediatrics, every patient with these genetic disorders should have a postnatal echocardiogram. T21 is usually associated with atrioventricular (30%-60%), atrial (16%-21%), or ventricular septal defects (14%-27%). TS is usually associated with left-sided heart disease. However, the spectrum of CHD in these genetic disorders is wider than those mentioned lesions. More cardiac surgical procedures are offered to these patients and that has influenced positively their life expectancy for some CHD conditions. Single ventricular anatomy is associated with high mortality in these genetic disorders (49% in T21 and 83%-91% in TS). The goal of this article is to describe the spectrum of CHD, screening guidelines, and cardiac surgical outcomes in patients with T21 or TS with CHD.

TÍTULO / TITLE:    - Genotype-phenotype correlation for congenital heart disease in Down syndrome through analysis of partial trisomy 21 cases.

REVISTA / JOURNAL:    - Genomics. 2017 Jun 23. pii: S0888-7543(17)30045-9. doi: 10.1016/j.ygeno.2017.06.004.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ygeno.2017.06.004

AUTORES / AUTHORS: - Pelleri MC; Vitale L et al.

INSTITUCIÓN / INSTITUTION: - Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Via Belmeloro 8, 40126 Bologna (BO), Italy.   lorenza.vitale@unibo.it

RESUMEN / SUMMARY: - Among Down syndrome (DS) children, 40-50% have congenital heart disease (CHD). Although trisomy 21 is not sufficient to cause CHD, three copies of at least part of chromosome 21 (Hsa21) increases the risk for CHD. In order to establish a genotype-phenotype correlation for CHD in DS, we built an integrated Hsa21 map of all described partial trisomy 21 (PT21) cases with sufficient indications regarding presence or absence of CHD (n=107), focusing on DS PT21 cases. We suggest a DS CHD candidate region on 21q22.2 (0.96Mb), being shared by most PT21 cases with CHD and containing three known protein-coding genes (DSCAM, BACE2, PLAC4) and four known non-coding RNAs (DSCAM-AS1, DSCAM-IT1, LINC00323, MIR3197). The characterization of a DS CHD candidate region provides a useful approach to identify specific genes contributing to the pathology and to orient further investigations and possibly more effective therapy in relation to the multifactorial pathogenesis of CHD.

TÍTULO / TITLE:    - Earlier Pulmonary Valve Replacement in Down Syndrome Patients Following Tetralogy of Fallot Repair.

REVISTA / JOURNAL:    - Pediatr Cardiol. 2017 Aug;38(6):1251-1256. doi: 10.1007/s00246-017-1653-2. Epub 2017 Jun 14.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s00246-017-1653-2

AUTORES / AUTHORS: - Sullivan RT; et al. Hill GD;

INSTITUCIÓN / INSTITUTION: - Pediatric Cardiology, Children’s Hospital of Wisconsin, 9000 W Wisconsin Ave, Milwaukee, WI, 53226, USA.   ghill@chw.org

RESUMEN / SUMMARY: - The association between Down syndrome and pulmonary hypertension could contribute to more severe pulmonary regurgitation after tetralogy of Fallot repair and possibly earlier pulmonary valve replacement. We compared cardiac magnetic resonance measures of pulmonary regurgitation and right ventricular dilation as well as timing of pulmonary valve replacement between those with and without Down syndrome after tetralogy of Fallot repair. Review of our surgical database from 2000 to 2015 identified patients with tetralogy of Fallot with pulmonary stenosis. Those with Down syndrome were compared to those without. The primary outcome of interest was time from repair to pulmonary valve replacement. Secondary outcomes included pulmonary regurgitation and indexed right ventricular volume on cardiac magnetic resonance imaging. The cohort of 284 patients included 35 (12%) with Down syndrome. Transannular patch repair was performed in 210 (74%). Down syndrome showed greater degree of pulmonary regurgitation (55 +/- 14 vs. 37 +/- 16%, p = 0.01) without a significantly greater rate of right ventricular dilation (p = 0.09). In multivariable analysis, Down syndrome (HR 2.3, 95% CI 1.2-4.5, p = 0.02) and transannular patch repair (HR 5.5, 95% CI 1.7-17.6, p = 0.004) were significant risk factors for valve replacement. Those with Down syndrome had significantly lower freedom from valve replacement (p = 0.03). Down syndrome is associated with an increased degree of pulmonary regurgitation and earlier pulmonary valve replacement after tetralogy of Fallot repair. These patients require earlier assessment by cardiac magnetic resonance imaging to determine timing of pulmonary valve replacement and evaluation for and treatment of preventable causes of pulmonary hypertension.

TÍTULO / TITLE:    - Concentrations of leptin, adiponectin and other metabolic parameters in non-obese children with Down syndrome.

REVISTA / JOURNAL:    - J Pediatr Endocrinol Metab. 2017 Aug 28;30(8):831-837. doi: 10.1515/jpem-2016-0422.

Enlace a la Editora de la Revista http://dx.doi.org/10.1515/jpem-2016-0422

AUTORES / AUTHORS: - Tenneti N; er al

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - BACKGROUND: Recent data indicates that adults with Down syndrome (DS) are at increased risk for cardiovascular disease (CVD) that significantly contributes to their morbidity and mortality. Although identification of cardiometabolic risk factors during childhood is desirable to design preventive interventions, the data on such risk factors in children with DS is scarce. The aim of this study was to study the cardiometabolic risk factors such as insulin resistance (IR), leptin and adiponectin concentrations, lipid abnormalities and leptin resistance in non-obese children with DS. METHODS: This cross-sectional case control study included karyotype confirmed trisomy-21 DS children aged 2-12 years and their matched healthy controls. After detailed anthropometry, weight, height and body mass index (BMI) standard deviation scores (SDSs) were calculated with reference data. Laboratory evaluation included determination of fasting lipid parameters, insulin, glucose, leptin and adiponectin concentrations. The homeostasis model assessment method (HOMA-IR) was used to assess IR and the ratio of leptin to BMI was used as an index of leptin resistance. RESULTS: Seventy-seven children (39 with DS and 38 controls) comprised the study cohort. The anthropometric parameters were similar in the two groups. Children with DS showed significantly higher mean leptin concentrations (2.098+/-1.68 ng/mL vs. 1.44+/-0.52 ng/mL, p-value: 0.00) and higher indices of leptin resistance (0.127+/-0.085 vs. 0.09+/-0.03, p-value: 0.001) as compared to controls. Fasting adiponectin concentrations were lower (20.64+/-19.87 ng/mL vs. 32.58+/-34.25 ng/mL, p-value: 0.21) and fasting glucose higher (89.25+/-8.12 mg/dL vs. 85.71+/-5.52 mg/dL, p-value: 0.06) in the DS group as compared to the controls but the differences did not reach statistical significance. The concentrations of insulin, various lipid parameters and calculated HOMA-IR values were similar in the two groups. In the DS group, five children wer

TÍTULO / TITLE:    - A rare case of pediatric primary cardiac tumor in a patient with Down syndrome.

REVISTA / JOURNAL:    - Asian Cardiovasc Thorac Ann. 2017 Jan 1:218492317721788. doi: 10.1177/0218492317721788.

Enlace a la Editora de la Revista http://dx.doi.org/10.1177/0218492317721788

AUTORES / AUTHORS: - Okada K; et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatric Cardiac Surgery, Saitama Medical University, International Medical Center, Hidaka City, Saitama, Japan.  

RESUMEN / SUMMARY: - Although hematological malignancies are a known complication of Down syndrome, few reports have described cases involving solid tumors. We describe the case of a 3-year-old Down syndrome girl with a primary solid cardiac tumor. Outpatient echocardiography after intracardiac repair of a ventricular septal defect at 6 months of age revealed a highly mobile pedunculated mass (8 x 9 mm) on the free wall of the right atrium. Due to potential incarceration of the mass in the tricuspid orifice, it was excised under extracorporeal circulation and cardiac arrest. Macroscopically, the tumor closely resembled a papillary fibroelastoma, although histopathological tests were inconclusive. 

TÍTULO / TITLE:    - Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension.

REVISTA / JOURNAL:    - BMC Cardiovasc Disord. 2017 Jul 4;17(1):177. doi: 10.1186/s12872-017-0569-3.

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s12872-017-0569-3

AUTORES / AUTHORS: - Beghetti M, Rudzinski A;

INSTITUCIÓN / INSTITUTION: - Pediatric Cardiology, Jagiellonian University, Golebia 24, 31-007, Cracow, Poland.  

RESUMEN / SUMMARY: - BACKGROUND: Despite the increased risk for pulmonary hypertension in children with Down syndrome, the response to treatment with targeted therapies for pulmonary hypertension in these patients is not well characterized. The Sildenafil in Treatment-naive children, Aged 1-17 years, with pulmonary arterial hypertension (STARTS-1) trial was a dose-ranging study of the short-term efficacy and safety of oral sildenafil in children with pulmonary arterial hypertension. We assessed the safety and efficacy of oral sildenafil in children with Down syndrome and pulmonary arterial hypertension. METHODS: This was a post-hoc analysis of children with Down syndrome and pulmonary arterial hypertension enrolled in the STARTS-1 trial. Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), and cardiac index (CI) were assessed at baseline and following 16 weeks of treatment with sildenafil. RESULTS: Of 234 patients randomized and treated in the STARTS-1 trial, 48 (20.5%) had Down syndrome. Although sildenafil produced dose-related reductions in PVRI and mPAP, compared with placebo, in non-Down syndrome patients and children developmentally able to exercise, this was not satisfactorily marked in patients with Down syndrome. The dose-related reductions in PVRI, compared with placebo, occurred in all subgroups, with the exception of the Down syndrome subgroup. Sildenafil appeared to be well tolerated in the Down syndrome subpopulation and the most frequently reported AEs were similar to those reported for the entire STARTS-1 population. CONCLUSION: Sildenafil treatment for 16 weeks had no effect on PVRI or mPAP in children with Down syndrome and pulmonary arterial hypertension. The results suggest that children with Down syndrome may be less responsive to sildenafil for pulmonary arterial hypertension, but the incomplete work-up for the etiology of pulmonary arterial hypertension may have introduced a potential bias. TRIAL

DENTAL - DENTAL

TÍTULO / TITLE:    - Salivary density of Streptococcus mutans and Streptococcus sobrinus and dental caries in children and adolescents with Down syndrome.

REVISTA / JOURNAL:    - J Appl Oral Sci. 2017 May-Jun;25(3):250-257. doi: 10.1590/1678-7757-2016-0241.

Enlace a la Editora de la Revista http://dx.doi.org/10.1590/1678-7757-2016-0241

AUTORES / AUTHORS: - Scalioni F; et al.

INSTITUCIÓN / INSTITUTION: - Universidade Federal de Juiz de Fora, Faculdade de Odontologia, Departamento de Odontopediatria, Juiz de Fora, MG, Brasil.  

RESUMEN / SUMMARY: - Objective: To assess and compare dental caries experience and salivary S. mutans, S. sobrinus, and streptococci counts between groups of Down syndrome and non-Down syndrome children and adolescents. Material and Methods: This study included a sample of 30 Down syndrome children and adolescents (G-DS) and 30 age- and sex-matched non-Down syndrome subjects (G-ND). Dental caries experience was estimated by the number of decayed, missing, and filled teeth in the primary dentition and the permanent dentition. Unstimulated whole saliva samples were collected from all participants. The fluorescence in situ hybridization technique was used to identify the presence and counts of the bacteria. The statistical analysis included chi-square, Student’s t-test and Spearman’s correlation. Results: The G-DS exhibited a significantly higher caries-free rate (p<0.001) and a lower S. mutans salivary density (p<0.001). No significant differences were found in the salivary densities of S. sobrinus or streptococci between the groups (p=0.09 and p=0.21, respectively). The salivary S. mutans or S. sobrinus densities were not associated with dental caries experience in neither group. Conclusion: The reduced dental caries experience observed in this group of Down syndrome children and adolescents cannot be attributed to lower salivary S. mutans densities, as determined with the fluorescence in situ hybridization technique.

TÍTULO / TITLE:    - Major salivary gland aplasia and hypoplasia in Down syndrome: review of the literature and report of a case.

REVISTA / JOURNAL:    - Clin Case Rep. 2017 May 4;5(6):939-944. doi: 10.1002/ccr3.975. eCollection 2017 Jun.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ccr3.975

AUTORES / AUTHORS: - Chadi MJ et al.

INSTITUCIÓN / INSTITUTION: - Faculty of Dentistry Universite de Montreal Montreal Quebec Canada.  

RESUMEN / SUMMARY: - Salivary gland aplasia and hypoplasia are rarely described in the medical literature. This article presents a case of aplasia and hypoplasia of the major salivary glands in a patient with Down syndrome. A literature review, as well as an overview of the diagnosis and management of this condition, is presented.

DERMATOLOGY - DERMATOLOGÍA

TÍTULO / TITLE:    - Prevalence of Hidradenitis Suppurativa Among Patients with Down Syndrome: a population based cross sectional analysis.

REVISTA / JOURNAL:    - Br J Dermatol. 2017 Jun 29. doi: 10.1111/bjd.15770.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/bjd.15770

AUTORES / AUTHORS: - Garg A; et al

INSTITUCIÓN / INSTITUTION: - Department of Dermatology, Hofstra Northwell School of Medicine, New Hyde Park, NY.  

RESUMEN / SUMMARY: - BACKGROUND: Hidradenitis Suppurativa (HS) has been linked to Down syndrome (DS). OBJECTIVE: To determine whether Down syndrome patients have a higher prevalence of HS, and whether diagnosis of HS occurs at an earlier age. METHODS: Cross-sectional analysis in a population sample of 11,936 DS patients and 16,813,290 non-DS patients. The primary outcome was diagnosis of HS. SNOMED-CT terms were used to identify patients with DS and HS. We used logistic regression models and significant interaction terms to evaluate the relationship between DS and HS. We also compared proportion of incident HS cases within five-year age groups to determine whether DS patients had earlier diagnosis of HS. RESULTS: Prevalence of HS among DS patients was 2.1%, compared to 0.3% for patients without DS (p<0.001). HS prevalence was greatest among DS patients who were aged 18-29 years. HS prevalence was not different between female and male DS patients or between white and non-white DS patients, after controlling for age, gender and obesity. Compared to those without DS, patients with the condition had increased odds of HS in unadjusted [OR 7.84, 95% CI 6.93-8.88] and adjusted [OR 5.24, 95% CI 4.62-5.94] analyses. Diagnosis of HS was made by the age of 29 years in 81.8% of patients with DS, compared to 34.0% of patients without the condition (p<0.001). CONCLUSION: HS is strongly associated with DS across demographic subgroups, and the disease may present earlier life in these patients. These findings have implications for surveillance and care of patients with DS. This article is protected by copyright. All rights reserved.

TÍTULO / TITLE:    - Hidradenitis Suppurativa in Down Syndrome: A Case Series.

REVISTA / JOURNAL:    - Pediatr Dermatol. 2017 Jul;34(4):461-464. doi: 10.1111/pde.13188. Epub 2017 Jun 21.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/pde.13188

AUTORES / AUTHORS: - Hamadah I; et al

INSTITUCIÓN / INSTITUTION: - King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.  

RESUMEN / SUMMARY: - BACKGROUND/OBJECTIVES: Many dermatologic and systemic diseases have been reported in association with hidradenitis suppurativa, but its association with Down syndrome is rarely mentioned in the literature. The objective of the current study was to assess the frequency of hidradenitis suppurativa in patients with Down syndrome who visited our clinic over 4 years. METHODS: We recorded the presenting complaints and dermatologic problems of patients with Down syndrome who visited our clinic from January 2011 to December 2014. Medical photographs were taken. Patients with hidradenitis suppurativa were assessed according to severity and treated with topical and systemic medications. RESULTS: Twenty-nine new patients with Down syndrome visited our clinic during this period. Eleven had hidradenitis suppurativa. Disease severity included Hurley stages I and II. CONCLUSION: The presence of hidradenitis suppurativa in 38% of patients with Down syndrome is far higher than would be expected by chance alone.

EAR/NASAL - OTORRINOLARINGOLOGÍA

TÍTULO / TITLE:    - Prevalence of pressure equalization tube placement and hearing loss in children with down syndrome.

REVISTA / JOURNAL:    - Int J Pediatr Otorhinolaryngol. 2017 Jul;98:48-52. doi: 10.1016/j.ijporl.2017.04.041. Epub 2017 Apr

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ijporl.2017.04.041

AUTORES / AUTHORS: - Bernardi GF; et al

INSTITUCIÓN / INSTITUTION: - Faculdade Evangelica do Parana, Curso de Medicina, Brazil.   gi.bernardi@yahoo.com.br

RESUMEN / SUMMARY: - OBJECTIVE: To determine the prevalence of pressure equalization tube (PET) placement and hearing loss in children with Down syndrome (DS). MATERIAL AND METHODS: We evaluated 90 DS children births between 1 and 11 years old and compared to 90 children without DS paired in sex and age. Medical records were analyzed consecutively. Were collected data about proceedings PET placement, age of the patient at each PET, adenoidectomy, tonsillectomy and results for audiometry and tympanometry. RESULTS: Among the 90 patients with DS, 49 (54.4%) were male, median age of 58 months (15-143 months). In this group, 75 PET were placed in 26/90 children (28.9%) mostly between 3 and 5 years old. In 10/26 (38.5%) was necessary PET replaced. When compared to the control group- 6/90 (6.7%)- children with DS presented OR = 13.7 (95% CI 4.0-47.3) times more likely to use PET. Adenoidectomy and tonsillectomy (44.4% and 42.2% respectively) were significantly more frequent in DS group. The prevalence of hearing loss was 32.1% in the right ear and 26.9% in the left ear. Type B timpanometry was found in more than half of the patients with DS. CONCLUSION: We found a 13-fold higher risk of PET in DS children, especially between the ages of 3-5 years. The high prevalence of hearing loss and PET placement in patients with DS reinforcing the importance of early and regular follow-up for hearing screening in this population, mostly in preschool-aged children.

TÍTULO / TITLE:    - Success of Tonsillectomy for Obstructive Sleep Apnea in Children With Down Syndrome.

REVISTA / JOURNAL:    - J Clin Sleep Med. 2017 Jul 14. pii: jc-17-00022.

AUTORES / AUTHORS: - Ingram DG et al

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common in children with Down syndrome (DS) and associated with significant morbidity. In the current study we examined polysomnographic outcomes of children with DS who underwent tonsillectomy. METHODS: A retrospective chart review of children with DS who underwent a tonsillectomy between 2009-2015 was performed. All children had either a concurrent adenoidectomy or had previously underwent an adenoidectomy. Children with preoperative and postoperative polysomnograms within 6 months of surgery were included in the analysis. Preoperative OSA severity was categorized by obstructive apnea-hypopnea index (OAHI) as follows: mild = 1.5-4.9 events/h; moderate = 5-9.9 events/h; severe> /= 10 events/h. RESULTS: Seventy-five children with DS met inclusion criteria. The cohort included 41 males and 34 females with mean age of 5.1 years (+/- 3.6 years), range of 0.51-16.60 years. Preoperative OSA severity was as follows, mild = 8/75; moderate = 16/75; severe = 51/75. Cure rates varied depending on definition: 12% for OAHI< 1 event/h and 21% for OAHI< 2 events/h. 48% had residual OAHI< 5 events/h. On postoperative PSG 16/75 saw resolution (OAHI< 2) in OSA; mild = 21/75; moderate = 20/75; severe = 18/75. 48% moderate/severe patients saw conversion to mild or cure. Overall, tonsillectomy resulted in significant improvements in multiple respiratory parameters, including OAHI (OAHI; 21.3 +/- 19.7 to 8.0 +/- 8.1, P< .001), percent sleep time with oxygen saturations < 90% (19.0 +/- 25.0 to 6.1 +/- 10.1, P< .001), and percent sleep time with end-tidal carbon dioxide above 50 mmHg (7.7 +/- 18.0 to 1.8 +/- 6.6, P = .001). Average asleep oxygen saturation was associated with postoperative OSA severity. CONCLUSIONS: Children with DS and OSA who undergo tonsillectomy experience improvements in both respiratory event frequency and gas exchange but approximately half still have moderate to severe residual OSA.

TÍTULO / TITLE:    - Audiologic Assessment in Adults With Down Syndrome.

REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2017 Jul;122(4):333-341. doi: 10.1352/1944-7558-122.4.333.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-122.4.333

AUTORES / AUTHORS: - Picciotti PM; et al.

INSTITUCIÓN / INSTITUTION: - Department of Gerontology, Neurosciences, Head and Neck and Orthopedics, Catholic University of the Sacred Heart, Rome, Italy.   Department of Gerontology, Neurosciences, Head and Neck and Orthopedics, Catholic University of the Sacred Heart, Rome, Italy.

RESUMEN / SUMMARY: - Increased life expectancy in persons with Down syndrome (DS) is associated with premature age-related changes. The aim of this study was to assess auditory function in adults with DS and to evaluate the prevalence of hearing loss in this population. Audiometric tests were performed in 72 adults with DS (mean age 37.3+/-10.1 years, 51.4% females). Air conduction pure tone average (PTA) thresholds at frequencies 0.5-1-2-4 kHz were calculated to assess hearing function. Hearing loss was present if the PTA threshold was > 20 dB hearing level. Higher frequencies of 4 and 8 kHz were also assessed. Hearing loss was shown in 47 (65.3%) participants. The prevalence of hearing loss increased with age, ranging from 42.86% in the 20-29 years group to 90.91% in the 50-59 years group. High frequencies (4 and 8 kHz) were more often impaired than other frequencies used to measure PTA. Thus, the study concluded hearing loss is common in adults with DS and shows a pattern compatible with precocious aging of the hearing system. Auditory evaluation is strongly recommended in adults with DS.

ENDOCRINOLOGY/NUTRITION - ENDOCRINOLOGÍA/NUTRICIÓN

TÍTULO / TITLE:    - Bone health in Down syndrome.

REVISTA / JOURNAL:    - Med Clin (Barc). 2017 Jul 21;149(2):78-82. doi: 10.1016/j.medcli.2017.04.020. Epub 2017 May 30.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.medcli.2017.04.020

AUTORES / AUTHORS: - Garcia-Hoyos M; Valero C; et al

INSTITUCIÓN / INSTITUTION: - Departamento de Medicina Interna, Hospital Universitario Marques de Valdecilla, Universidad de Cantabria, Instituto de Investigacion Sanitaria Valdecilla (IDIVAL), Santander, España   mirvdc@humv.es

RESUMEN / SUMMARY: - Patients with Down syndrome have a number of risk factors that theoretically could predispose them to osteoporosis, such as early aging, development disorders, reduced physical activity, limited sun exposure, frequent comorbidities and use of drug therapies which could affect bone metabolism. In addition, the bone mass of these people may be affected by their anthropometric and body composition peculiarities. In general terms, studies in adults with Down syndrome reported that these people have lower areal bone mineral density (g/cm2) than the general population. However, most of them have not taken the smaller bone size of people with Down syndrome into account. In fact, when body mineral density is adjusted by bone size and we obtain volumetric body mineral density (g/cm3), the difference between both populations disappears. On the other hand, although people with Down syndrome have risk factor of hypovitaminosis D, the results of studies regarding 25(OH)D in this population are not clear. Likewise, the studies about biochemical bone markers or the prevalence of fractures are not conclusive.

TÍTULO / TITLE:    - Nonalcoholic Fatty Liver Disease in Italian Children with Down Syndrome: Prevalence and Correlation with Obesity-Related Features.

REVISTA / JOURNAL:    - J Pediatr. 2017 Jun 26. pii: S0022-3476(17)30773-4. doi: 10.1016/j.jpeds.2017.05.077.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jpeds.2017.05.077

AUTORES / AUTHORS: - Valentini D; et al.

INSTITUCIÓN / INSTITUTION: - Pediatric and Infectious Disease Unit, Bambino Gesu Children’s Hospital, Institute for Research and Health Care (IRCCS), Rome, Italy.   diletta.valentini@opbg.net

RESUMEN / SUMMARY: - OBJECTIVE: To assess the prevalence of overweight/obesity in a cohort of Italian children with Down syndrome (DS) and to investigate the correlation of both obesity and DS with nonalcoholic fatty liver disease (NAFLD). STUDY DESIGN: We enrolled 280 children with DS (age range 5-18 years), who were referred to the DS outpatient clinic of the Bambino Gesu Children’s Hospital in Rome. For all children, we collected the clinical history and measured anthropometric variables. Eighty-four of 280 children with DS were selected to undergo liver ultrasound scanning to evaluate the presence of NAFLD. RESULTS: Italian children with DS exhibited a prevalence of 19.64% for overweight and 12.14% for obesity. The prevalence of NAFLD in nonobese (45%) and overweight/obese (82%) children with DS is greater than in the European pediatric nonobese (5.7%) or obese population (33%). Moreover, the severity of liver brightness on ultrasound scan correlated positively with body mass index, triglycerides, low-density lipoprotein-cholesterol, and leptin levels and negatively with adiponectin. CONCLUSIONS: We demonstrated that, independently from the obese phenotype, children with DS display a greater risk to develop NAFLD than the general pediatric population.

TÍTULO / TITLE:    - Caregiver-Reported Quality of Life in Youth with Down Syndrome.

REVISTA / JOURNAL:    - J Pediatr. 2017 Jul 24. pii: S0022-3476(17)30923-X. doi: 10.1016/j.jpeds.2017.06.073.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jpeds.2017.06.073

AUTORES / AUTHORS: - Xanthopoulos MS; et al.

INSTITUCIÓN / INSTITUTION: - Department of Child and Adolescent Psychiatry and Behavioral Sciences, Children’s Hospital of Philadelphia, Philadelphia, PA.   xanthop@email.chop.edu

RESUMEN / SUMMARY: - OBJECTIVES: To describe caregiver-reported quality of life (QOL) in youth with Down syndrome (DS) and to examine the role of obesity on QOL. STUDY DESIGN: Caregivers of youth with and without DS aged 10 through 20 years completed questionnaires examining QOL (Pediatric Quality of Life Questionnaire) and weight-related QOL (Impact of Weight on Quality of Life - Kids). Age- and sex-specific z scores were generated for body mass index. Obesity was defined as a body mass index >/=95th percentile for age and sex. RESULTS: Caregiver-reported Total QOL, Physical Health, and Psychosocial Health summary scores were all lower in the DS group compared with the non-DS controls (P < .001). Social and School Functioning were also lower (P < .001), but Emotional Functioning did not differ between DS and non-DS groups (P = .31). Physical Functioning (P = .003) and Total scores (P = .03) differed between youth without DS with and without obesity, but no differences were reported between youth with DS with and without obesity. On the Impact of Weight on Quality of Life - Kids, caregivers of youth with DS reported greater Body Esteem (P = .020) and Social Life scores (P = .03) than caregivers of non-DS youth. Caregivers of youth with obesity, regardless of DS status, reported significantly lower weight-specific QOL scores than caregivers of youth without obesity. CONCLUSION: Caregivers reported lower QOL in youth with DS compared with youth without DS with the exception of emotional functioning. Obesity influences most domains of weight-related QOL in youth with and without DS; therefore, providers should address weight concerns in youth with obesity even in the presence of DS. CLINICAL TRIAL REGISTRATION: NCT01821300.

TÍTULO / TITLE:    - Oral sucking habits among children with Down syndrome and cerebral palsy.

REVISTA / JOURNAL:    - Spec Care Dentist. 2017 Jul;37(4):176-180. doi: 10.1111/scd.12231.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/scd.12231

AUTORES / AUTHORS: - Carneiro NCR; et al.

INSTITUCIÓN / INSTITUTION: - Faculty of Dentistry, Department of Pediatric Dentistry and Orthodontics, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.  

RESUMEN / SUMMARY: - AIMS: Identify factors associated with the presence of oral sucking habits among children with Down syndrome (DS) and cerebral palsy (CP). METHODS: The sample consisted of 181 children with DS or CP from two public healthcare institutions that treat children with special needs in the city of Rio de Janeiro, Brazil. The children’s mothers answered a questionnaire about the individual and behavioral characteristics and the medical history of their children. The study was approved by the Research Ethics Committee of Universidade Federal de Minas Gerais. RESULTS: The presence of oral sucking habits (bottle feeding and pacifier/finger sucking) was observed in 83.0% of children. Children with artificial sucking habits had a 3.42 times greater chance of having a history of throat infection during the previous 6 months (5.61 to 48). A mother in the group of children with oral sucking habits had a 10.28 chance of not having breastfed her child (2.86 to 36.93). CONCLUSION: The history of throat infections in the preceding 6 months and the lack of breastfeeding were associated with the presence of oral sucking habits in children with DS and CP.

TÍTULO / TITLE:    - Oral sucking habits among children with Down syndrome and cerebral palsy.

REVISTA / JOURNAL:    - Spec Care Dentist. 2017 Jul;37(4):176-180. doi: 10.1111/scd.12231.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/scd.12231

AUTORES / AUTHORS: - Carneiro NCR; et al.

INSTITUCIÓN / INSTITUTION: - Faculty of Dentistry, Department of Pediatric Dentistry and Orthodontics, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.  

RESUMEN / SUMMARY: - AIMS: Identify factors associated with the presence of oral sucking habits among children with Down syndrome (DS) and cerebral palsy (CP). METHODS: The sample consisted of 181 children with DS or CP from two public healthcare institutions that treat children with special needs in the city of Rio de Janeiro, Brazil. The children’s mothers answered a questionnaire about the individual and behavioral characteristics and the medical history of their children. The study was approved by the Research Ethics Committee of Universidade Federal de Minas Gerais. RESULTS: The presence of oral sucking habits (bottle feeding and pacifier/finger sucking) was observed in 83.0% of children. Children with artificial sucking habits had a 3.42 times greater chance of having a history of throat infection during the previous 6 months (5.61 to 48). A mother in the group of children with oral sucking habits had a 10.28 chance of not having breastfed her child (2.86 to 36.93). CONCLUSION: The history of throat infections in the preceding 6 months and the lack of breastfeeding were associated with the presence of oral sucking habits in children with DS and CP.

TÍTULO / TITLE:    - Concentrations of leptin, adiponectin and other metabolic parameters in non-obese children with Down syndrome.

REVISTA / JOURNAL:    - J Pediatr Endocrinol Metab. 2017 Aug 28;30(8):831-837. doi: 10.1515/jpem-2016-0422.

Enlace a la Editora de la Revista http://dx.doi.org/10.1515/jpem-2016-0422

AUTORES / AUTHORS: - Tenneti N; er al

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - BACKGROUND: Recent data indicates that adults with Down syndrome (DS) are at increased risk for cardiovascular disease (CVD) that significantly contributes to their morbidity and mortality. Although identification of cardiometabolic risk factors during childhood is desirable to design preventive interventions, the data on such risk factors in children with DS is scarce. The aim of this study was to study the cardiometabolic risk factors such as insulin resistance (IR), leptin and adiponectin concentrations, lipid abnormalities and leptin resistance in non-obese children with DS. METHODS: This cross-sectional case control study included karyotype confirmed trisomy-21 DS children aged 2-12 years and their matched healthy controls. After detailed anthropometry, weight, height and body mass index (BMI) standard deviation scores (SDSs) were calculated with reference data. Laboratory evaluation included determination of fasting lipid parameters, insulin, glucose, leptin and adiponectin concentrations. The homeostasis model assessment method (HOMA-IR) was used to assess IR and the ratio of leptin to BMI was used as an index of leptin resistance. RESULTS: Seventy-seven children (39 with DS and 38 controls) comprised the study cohort. The anthropometric parameters were similar in the two groups. Children with DS showed significantly higher mean leptin concentrations (2.098+/-1.68 ng/mL vs. 1.44+/-0.52 ng/mL, p-value: 0.00) and higher indices of leptin resistance (0.127+/-0.085 vs. 0.09+/-0.03, p-value: 0.001) as compared to controls. Fasting adiponectin concentrations were lower (20.64+/-19.87 ng/mL vs. 32.58+/-34.25 ng/mL, p-value: 0.21) and fasting glucose higher (89.25+/-8.12 mg/dL vs. 85.71+/-5.52 mg/dL, p-value: 0.06) in the DS group as compared to the controls but the differences did not reach statistical significance. The concentrations of insulin, various lipid parameters and calculated HOMA-IR values were similar in the two groups. In the DS group, five children wer

TÍTULO / TITLE:    - Recurrent insulinoma in a 10-year-old boy with Down’s syndrome.

REVISTA / JOURNAL:    - Endocrinol Diabetes Metab Case Rep. 2017 May 24;2017. pii: 16-0155. doi: 10.1530/EDM-16-0155. eColle

Enlace a la Editora de la Revista http://dx.doi.org/10.1530/EDM-16-0155

AUTORES / AUTHORS: - Ahmad N; et al.

INSTITUCIÓN / INSTITUTION: - King Faisal Specialist Hospital and Research Centre, Pediatrics, Jeddah, SASaudi Arabia.  

RESUMEN / SUMMARY: - An insulinoma is a rare tumour with an incidence of four cases per million per year in adults. The incidence in children is not established. There is limited literature available in children with insulinoma, and only one case is reported in association with Down’s syndrome in adults. Insulinoma diagnosis is frequently missed in adults as well as in children. The Whipple triad is the most striking feature although it has limited application in young children. Hypoglycaemia with elevated insulin, C-peptide and absent ketones is highly suggestive of hyperinsulinism. We present a case of 10-year-old boy with Down’s syndrome with recurrent insulinoma. He was initially misdiagnosed as having an adrenal insufficiency and developed cushingoid features and obesity secondary to hydrocortisone treatment and excessive sugar intake. The tumour was successfully localised in the head of the pancreas with an MRI and octreotide scan on first presentation. Medical treatment with diazoxide and octreotide could not achieve normal blood glucose levels. The insulinoma was laparoscopically enucleated and pathological examination confirmed a neuroendocrine tumour. Subsequently, he had complete resolution of symptoms. He had a recurrence after 2 years with frequent episodes of hypoglycaemia. The biochemical workup was suggestive of hyperinsulinism. MRI and PET scan confirmed the recurrence at the same site (head of the pancreas). He had an open laparotomy for insulinoma resection. The pathology was consistent with benign insulinoma, and subsequently, he had complete resolution of symptoms. LEARNING POINTS: Insulinoma is a very rare tumour in children; it should be considered in the differential diagnosis of hypoglycaemia with absent ketones.Refractory neurological symptoms like seizure, migraine, mood changes and regression of learning abilities should suggest evaluation for hypoglycaemia.MRI with contrast and PET scan would localise the majority of pancreatic beta islet cell lesions.Medica

EPIDEMIOLOGY - EPIDEMIOLOGÍA

TÍTULO / TITLE:    - Demographics and co-occurring conditions in a clinic-based cohort with Down syndrome in the United Arab Emirates.

REVISTA / JOURNAL:    - Am J Med Genet A. 2017 Jul 7. doi: 10.1002/ajmg.a.38338.

Enlace a la Editora de la Revista http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=28686324&dopt=Abstract

AUTORES / AUTHORS: - Corder JP et al. Al Ahbabi FJS;

INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Tawam Hospital in Affiliation With Johns Hopkins International, Al Ain, United Arab Emirates.  

RESUMEN / SUMMARY: - The majority of studies describing demographics and co-occurring conditions in cohorts with Down syndrome come from regions outside of the Middle East, mainly from Europe and North America. This paper describes demographics and co-occurring conditions in a hospital-based cohort of individuals with Down syndrome living in the Middle Eastern country of the United Arab Emirates (UAE). The first dedicated Down syndrome clinic in the UAE was established in 2012 at Tawam Hospital in Al Ain. This paper describes a clinic-based cohort of 221 participants over 4 years from the Gulf Down Syndrome Registry, a new Down syndrome database and contact registry created at Tawam Hospital. Key demographic findings include mean maternal age of 37 years, among the highest described in the literature. Sixty-two percent of mothers are> 35 years. Over 90% of mothers received post-natal diagnosis of Down syndrome. High sex ratio, parental consanguinity, and large family size also characterize the group. The spectrum of many co-occurring conditions mirrors that of previously described populations, with some notable differences. Cardiovascular malformations are well represented, however, atrioventricular canal is not the most common. Genitourinary conditions are common, as evidenced by 12% of males with hypospadias and 15% with undescended testes. Glucose-6-phosphate dehydrogenase deficiency, alpha thalassemia trait, hypovitaminosis D, and dental caries are common in our cohort. This study describes a large hospital-based group with Down syndrome presenting to a new dedicated Down syndrome clinic in the UAE, highlighting unique demographic and co-occurring conditions found in that population.

TÍTULO / TITLE:    - Fetopathological examination for the fetuses with Down syndrome in Tunisia: Epidemiological study and associated malformations.

REVISTA / JOURNAL:    - Pathol Res Pract. 2017 May 8. pii: S0344-0338(17)30011-0. doi: 10.1016/j.prp.2017.05.001.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.prp.2017.05.001

AUTORES / AUTHORS: - Aloui M; et al

INSTITUCIÓN / INSTITUTION: - Faculte des Sciences de Bizerte, Universite de Carthage, 7021 Zarzouna, Bizerte, Tunisia; UR 06/SP14 Troubles du developpement embryo-foetal et placentaire, Service d’embryo-foetopathologie, Centre de Maternite et de Neonatologie de Tunis,   loui.meriem@gmail.com

RESUMEN / SUMMARY: - BACKGROUND: For Down syndrome (DS), traditional epidemiological studies to determine the prevalence, cause, and clinical significance of the syndrome have been conducted over the last 100 years. In Tunisia, the current work is the first in-depth study in epidemiology of DS from fetopathological data. AIM OF THE STUDY: The aim of this epidemiological study was to determine the impact of some feto-maternal characteristics in occurrence of DS and to search the frequency of associated congenital malformations with this syndrome. METHODS: Our retrospective study was realized for 144 fetuses with DS among 9321 autopsied fetuses in embryo-fetopathological service between 1994 and 2011. RESULTS: In our study, the majority of mothers (72.91%) were 35 years and older, with a statistically significant difference (p<10-6, OR=16.7, CI=8.7-32.4). The abnormalities of extremities (31%) were the most common fetal abnormalities followed by facial (23.51%) and digestive abnormalities (19.63%). CONCLUSION: One of the main conclusions of this research is that the most common risk factor for DS is maternal age. On the other hand, the type and the frequency of associated congenital anomalies with DS are still controversial.

GASTROENTEROLOGY - GASTROENTEROLOGÍA

TÍTULO / TITLE:    - An Unusual Manifestation of Celiac Disease in an Adolescent With Down Syndrome and Graves Disease.

REVISTA / JOURNAL:    - J Pediatr Gastroenterol Nutr. 2017 Jul;65(1):e20-e22. doi: 10.1097/MPG.0000000000000858.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/MPG.0000000000000858

AUTORES / AUTHORS: - Creo AL; et al.

INSTITUCIÓN / INSTITUTION: - The Warren Alpert Medical School of Brown University, Providence, RI daggerDivision of Pediatric Gastroenterology double daggerDivision of Pediatric Endocrinology, University of Massachusetts Medical School, Worcester, MA.  

RESUMEN / SUMMARY: -

TÍTULO / TITLE:    - Nonalcoholic Fatty Liver Disease in Italian Children with Down Syndrome: Prevalence and Correlation with Obesity-Related Features.

REVISTA / JOURNAL:    - J Pediatr. 2017 Jun 26. pii: S0022-3476(17)30773-4. doi: 10.1016/j.jpeds.2017.05.077.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jpeds.2017.05.077

AUTORES / AUTHORS: - Valentini D; et al.

INSTITUCIÓN / INSTITUTION: - Pediatric and Infectious Disease Unit, Bambino Gesu Children’s Hospital, Institute for Research and Health Care (IRCCS), Rome, Italy.   diletta.valentini@opbg.net

RESUMEN / SUMMARY: - OBJECTIVE: To assess the prevalence of overweight/obesity in a cohort of Italian children with Down syndrome (DS) and to investigate the correlation of both obesity and DS with nonalcoholic fatty liver disease (NAFLD). STUDY DESIGN: We enrolled 280 children with DS (age range 5-18 years), who were referred to the DS outpatient clinic of the Bambino Gesu Children’s Hospital in Rome. For all children, we collected the clinical history and measured anthropometric variables. Eighty-four of 280 children with DS were selected to undergo liver ultrasound scanning to evaluate the presence of NAFLD. RESULTS: Italian children with DS exhibited a prevalence of 19.64% for overweight and 12.14% for obesity. The prevalence of NAFLD in nonobese (45%) and overweight/obese (82%) children with DS is greater than in the European pediatric nonobese (5.7%) or obese population (33%). Moreover, the severity of liver brightness on ultrasound scan correlated positively with body mass index, triglycerides, low-density lipoprotein-cholesterol, and leptin levels and negatively with adiponectin. CONCLUSIONS: We demonstrated that, independently from the obese phenotype, children with DS display a greater risk to develop NAFLD than the general pediatric population.

TÍTULO / TITLE:    - Necrotizing Enterocolitis Incidence, Characteristics, and Outcomes in Neonatal Down Syndrome Patients.

REVISTA / JOURNAL:    - Am J Perinatol. 2017 Jun 2. doi: 10.1055/s-0037-1603688.

Enlace a la Editora de la Revista http://dx.doi.org/10.1055/s-0037-1603688

AUTORES / AUTHORS: - Cua CL;et al

INSTITUCIÓN / INSTITUTION: - Heart Center, Nationwide Children’s Hospital, Columbus, Ohio.  

RESUMEN / SUMMARY: -

TÍTULO / TITLE:    - Congenital duodenal and multiple jejunal atresia with malrotation in a patient with Down syndrome.

REVISTA / JOURNAL:    - Congenit Anom (Kyoto). 2017 Jul 4. doi: 10.1111/cga.12236.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/cga.12236

AUTORES / AUTHORS: - Shironomae T, Satomi M; et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatric Surgery, Kanazawa Medical University, Kahoku, Ishikawa, Japan.  

RESUMEN / SUMMARY: -

GENETICS - GENÉTICA

TÍTULO / TITLE:    - Genotype-phenotype correlation for congenital heart disease in Down syndrome through analysis of partial trisomy 21 cases.

REVISTA / JOURNAL:    - Genomics. 2017 Jun 23. pii: S0888-7543(17)30045-9. doi: 10.1016/j.ygeno.2017.06.004.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ygeno.2017.06.004

AUTORES / AUTHORS: - Pelleri MC; Vitale L et al.

INSTITUCIÓN / INSTITUTION: - Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Via Belmeloro 8, 40126 Bologna (BO), Italy.   lorenza.vitale@unibo.it

RESUMEN / SUMMARY: - Among Down syndrome (DS) children, 40-50% have congenital heart disease (CHD). Although trisomy 21 is not sufficient to cause CHD, three copies of at least part of chromosome 21 (Hsa21) increases the risk for CHD. In order to establish a genotype-phenotype correlation for CHD in DS, we built an integrated Hsa21 map of all described partial trisomy 21 (PT21) cases with sufficient indications regarding presence or absence of CHD (n=107), focusing on DS PT21 cases. We suggest a DS CHD candidate region on 21q22.2 (0.96Mb), being shared by most PT21 cases with CHD and containing three known protein-coding genes (DSCAM, BACE2, PLAC4) and four known non-coding RNAs (DSCAM-AS1, DSCAM-IT1, LINC00323, MIR3197). The characterization of a DS CHD candidate region provides a useful approach to identify specific genes contributing to the pathology and to orient further investigations and possibly more effective therapy in relation to the multifactorial pathogenesis of CHD.

TÍTULO / TITLE:    - Age exacerbates abnormal protein expression in a mouse model of Down syndrome.

REVISTA / JOURNAL:    - Neurobiol Aging. 2017 Sep;57:120-132. doi: 10.1016/j.neurobiolaging.2017.05.002. Epub 2017 May 10.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.neurobiolaging.2017.05.002

AUTORES / AUTHORS: - Ahmed MM; Gardiner KJ et al

INSTITUCIÓN / INSTITUTION: - Linda Crnic Institute for Down Syndrome, Aurora, CO, USA; Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, CO, USA; Human Medical Genetics and Genomics, and Neuroscience Programs, University of Colorado De   Katheleen.gardiner@ucdenver.edu

RESUMEN / SUMMARY: - The Ts65Dn is a popular mouse model of Down syndrome (DS). It displays DS-relevant features of learning/memory deficits and age-related loss of functional markers in basal forebrain cholinergic neurons. Here we describe protein expression abnormalities in brain regions of 12-month-old male Ts65Dn mice. We show that the magnitudes of abnormalities of human chromosome 21 and non-human chromosome 21 orthologous proteins are greater at 12 months than at approximately 6 months. Age-related exacerbations involve the number of components affected in the mechanistic target of rapamycin pathway, the levels of components of the mitogen-activated protein kinase pathway, and proteins associated with Alzheimer’s disease. Among brain regions, the number of abnormalities in cerebellum decreased while the number in cortex greatly increased with age. The Ts65Dn is being used in preclinical evaluations of drugs for cognition in DS. Most commonly, drug evaluations are tested in approximately 4- to 6-month-old mice. Data on age-related changes in magnitude and specificity of protein perturbations can be used to understand the molecular basis of changes in cognitive ability and to predict potential age-related specificities in drug efficacies.

TÍTULO / TITLE:    - Chromosome 21-Encoded microRNAs (mRNAs): Impact on Down’s Syndrome and Trisomy-21 Linked Disease.

REVISTA / JOURNAL:    - Cell Mol Neurobiol. 2017 Jul 7. doi: 10.1007/s10571-017-0514-0.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s10571-017-0514-0

AUTORES / AUTHORS: - Alexandrov PN; Lukiw WJ;

INSTITUCIÓN / INSTITUTION: - LSU Neuroscience Center, Louisiana State University Health Science Center, 2020 Gravier Street, Suite 904, New Orleans, LA, 70112-2272, USA.   wlukiw@lsuhsc.edu

RESUMEN / SUMMARY: - Down’s syndrome (DS; also known as trisomy 21; T21) is caused by a triplication of all or part of human chromosome 21 (chr21). DS is the most common genetic cause of intellectual disability attributable to a naturally-occurring imbalance in gene dosage. DS incurs huge medical, healthcare, and socioeconomic costs, and there are as yet no effective treatments for this incapacitating human neurogenetic disorder. There is a remarkably wide variability in the ‘phenotypic spectrum’ associated with DS; the progression of symptoms and the age of DS onset fluctuate, and there is further variability in the biophysical nature of the chr21 duplication. Besides the cognitive disruptions and dementia in DS patients other serious health problems such as atherosclerosis, altered lipogenesis, Alzheimer’s disease, amyotrophic lateral sclerosis (Lou Gehrig’s disease), autoimmune disease, various cancers including lymphoma, leukemia, glioma and glioblastoma, status epilepticus, congenital heart disease, hypotonia, manic depression, prostate cancer, Usher syndrome, motor disorders, Hirschsprung disease, and various physical anomalies such as early aging occur at elevated frequencies, and all are part of the DS ‘phenotypic spectrum.’ This communication will review the genetic link between these fore-mentioned diseases and a small group of just five stress-associated microRNAs (miRNAs)-that include let-7c, miRNA-99a, miRNA-125b, miRNA-155, and miRNA-802-encoded and clustered on the long arm of human chr21 and spanning the chr21q21.1-chr21q21.3 region.

TÍTULO / TITLE:    - Co-occurring Down syndrome and SUCLA2-related mitochondrial depletion syndrome.

REVISTA / JOURNAL:    - Am J Med Genet A. 2017 Jul 27. doi: 10.1002/ajmg.a.38351.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.38351

AUTORES / AUTHORS: - Couser NL et al.

INSTITUCIÓN / INSTITUTION: - University of North Carolina School of Medicine, Chapel Hill, North Carolina.  

RESUMEN / SUMMARY: - Mitochondrial DNA depletion syndrome 5 (MIM 612073) is a rare autosomal recessive disorder caused by homozygous or compound heterozygous pathogenic variants in the beta subunit of the succinate-CoA ligase gene located within the 13q14 band. We describe two siblings of Hispanic descent with SUCLA2-related mitochondrial depletion syndrome (encephalomyopathic form with methylmalonic aciduria); the older sibling is additionally affected with trisomy 21. SUCLA2 sequencing identified homozygous p.Arg284Cys pathogenic variants in both patients. This mutation has previously been identified in four individuals of Italian and Caucasian descent. The older sibling with concomitant disease has a more severe phenotype than what is typically described in patients with either SUCLA2-related mitochondrial depletion syndrome or Down syndrome alone. The younger sibling, who has a normal female chromosome complement, is significantly less affected compared to her brother. While the clinical and molecular findings have been reported in about 50 patients affected with a deficiency of succinate-CoA ligase caused by pathogenic variants in SUCLA2, this report describes the first known individual affected with both a mitochondrial depletion syndrome and trisomy 21.

GROWTH/DEVELOPMENT - CRECIMIENTO/DESARROLLO

TÍTULO / TITLE:    - Anthropometric charts and congenital anomalies in newborns with Down syndrome.

REVISTA / JOURNAL:    - Am J Med Genet A. 2017 Aug;173(8):2166-2175. doi: 10.1002/ajmg.a.38305. Epub 2017 Jun 2.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ajmg.a.38305

AUTORES / AUTHORS: - Mircher C et al

INSTITUCIÓN / INSTITUTION: - Jerome Lejeune Institute, Paris, France.  

RESUMEN / SUMMARY: - The objectives of this study were to obtain updated neonatal measurements in French newborns with Down Syndrome (DS) according to their gestational age, and to assess the frequency and distribution of congenital anomalies. Data on congenital malformations, birth weight, birth length and birth occipito-frontal circumference (OFC) according to the gestational age was gathered from 1,030 babies, born between 1980 and 2010. The mean gestational age was 38 weeks from the date of the last menstrual period (LMP) (range: 29-42 weeks). Repartition of complications was found to be similar to previous studies, with no difference according to the date of birth. For girls born after 37 weeks, the mean birth weight was 3,012 +/- 430 g, the mean birth length was 47.7 +/- 2 cm, and the mean birth OFC was 33 +/- 1.4 cm. For boys born after 37 weeks, the mean birth weight was 3,103 +/- 459, the mean birth length was 48.4 +/- 2.2 cm, and the mean birth OFC was 33.2 +/- 1.4 cm. We did not find any difference in these measurements when we compared children born before 1997 and after 2007. When compared to the general population (French data and WHO charts), newborns with DS have a more pronounced difference in their birth length and their birth OFC (15-25th) than in their birth weight (25-50th). The shape of the growth curves shows that growth velocity decreases during the last weeks of gestation in all measurements, which suggests that the modal age for delivery could be earlier in DS newborns than in the general population.

TÍTULO / TITLE:    - Bone health in Down syndrome.

REVISTA / JOURNAL:    - Med Clin (Barc). 2017 Jul 21;149(2):78-82. doi: 10.1016/j.medcli.2017.04.020. Epub 2017 May 30.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.medcli.2017.04.020

AUTORES / AUTHORS: - Garcia-Hoyos M; Valero C; et al

INSTITUCIÓN / INSTITUTION: - Departamento de Medicina Interna, Hospital Universitario Marques de Valdecilla, Universidad de Cantabria, Instituto de Investigacion Sanitaria Valdecilla (IDIVAL), Santander, España.   mirvdc@humv.es

RESUMEN / SUMMARY: - Patients with Down syndrome have a number of risk factors that theoretically could predispose them to osteoporosis, such as early aging, development disorders, reduced physical activity, limited sun exposure, frequent comorbidities and use of drug therapies which could affect bone metabolism. In addition, the bone mass of these people may be affected by their anthropometric and body composition peculiarities. In general terms, studies in adults with Down syndrome reported that these people have lower areal bone mineral density (g/cm2) than the general population. However, most of them have not taken the smaller bone size of people with Down syndrome into account. In fact, when body mineral density is adjusted by bone size and we obtain volumetric body mineral density (g/cm3), the difference between both populations disappears. On the other hand, although people with Down syndrome have risk factor of hypovitaminosis D, the results of studies regarding 25(OH)D in this population are not clear. Likewise, the studies about biochemical bone markers or the prevalence of fractures are not conclusive.

GYNECOLOGY - GINECOLOGÍA

TÍTULO / TITLE:    - Effect of extended oral contraception use on the prevalence of fetal trisomy 21 in women aged at least 35 years.

REVISTA / JOURNAL:    - Int J Gynaecol Obstet. 2017 Sep;138(3):261-266. doi: 10.1002/ijgo.12238. Epub 2017 Jul 5.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/ijgo.12238

AUTORES / AUTHORS: - Horanyi D; et al.

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Conjoint Szent Istvan and Szent Laszlo Hospital, Budapest, Hungary.  

RESUMEN / SUMMARY: - OBJECTIVE: To study factors influencing the number of ovulations in reproductive life as risk factors for common trisomies. METHODS: The present observational study examined data from genetic counseling sessions performed at the 1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary, between September 1, 2013, and September 1, 2015, and retrieved data on patients of advanced maternal age (>/=35 years) who had fetal trisomy 21, 18, or 13 confirmed. Consecutive patients of advanced maternal age with genetic amniocentesis-confirmed healthy fetal karyotypes were also included as a control group. Medical record details were confirmed through telephone interviews with patients; the estimated ovulation number was calculated and compared among patients, as were factors contributing to the number of ovulations each patient had. RESULTS: Data from 12 776 genetic counseling situations were examined; 35 patients with fetal trisomies and 100 patients in the control group were interviewed. Shorter mean length of oral contraceptive pill use before trisomic pregnancy (P<0.001) and a lower estimated ovulation number (P=0.012) were identified among patients with pregnancies with fetal trisomies. CONCLUSION: Fewer ovulatory cycles, potentially resulting from longer oral contraceptive pill use, was associated with healthy fetal karyotypes among patients of advanced reproductive age.

HEMATOLOGY/ONCOLOGY - HEMATOLOGÍA/ONCOLOGÍA

TÍTULO / TITLE:    - Down syndrome, RASopathies, and other rare syndromes.

REVISTA / JOURNAL:    - Semin Hematol. 2017 Apr;54(2):123-128. doi: 10.1053/j.seminhematol.2017.04.008. Epub 2017 Apr 28.

Enlace a la Editora de la Revista http://dx.doi.org/10.1053/j.seminhematol.2017.04.008

AUTORES / AUTHORS: - Kratz CP; Izraeli S

INSTITUCIÓN / INSTITUTION: - Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.   kratz.christian@mh-hannover.de

RESUMEN / SUMMARY: - In this article we discuss the occurrence of myeloid neoplasms in patients with a range of syndromes that are due to germline defects of the RAS signaling pathway and in patients with trisomy 21. Both RAS mutations and trisomy 21 are common somatic events contributing to leukemogenis. Thus, the increased leukemia risk observed in children affected by these conditions is biologically highly plausible. Children with myeloid neoplasms in the context of these syndromes require different treatments than children with sporadic myeloid neoplasms and provide an opportunity to study the role of trisomy 21 and RAS signaling during leukemogenesis and development.

TÍTULO / TITLE:    - Predispositions to Leukemia in Down Syndrome and Other Hereditary Disorders.

REVISTA / JOURNAL:    - Curr Treat Options Oncol. 2017 Jul;18(7):41. doi: 10.1007/s11864-017-0485-x.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s11864-017-0485-x

AUTORES / AUTHORS: - Saida S;

INSTITUCIÓN / INSTITUTION: - Oncogenesis and Development Section, National Human Genome Research Institute, National Institutes of Health, Bldg 49, RM 4A25 49 Convent DR, Bethesda, MD, 20892, USA.   satoshi.saida@nih.gov

RESUMEN / SUMMARY: - OPINION STATEMENT: Leukemia is the most common pediatric cancer and accounts for approximately one third of childhood malignancies. There are germline genetic alterations that significantly increase the risk of developing hematopoietic malignancies in childhood. In this review, we describe a number of these hereditary disorders and their clinical features. These predispositions to cancer syndromes can be attributed to DNA repair/genetic instability, RAS pathway dysfunction, bone marrow failure, telomeropathies, immunodeficiencies, transcription factor abnormalities, pure familial leukemia, and aneuploidy. We focus especially on acute myeloid leukemia associated with Down syndrome, but also include other hereditary syndromes in this review. Recent advances in high-throughput genotyping technology have identified new genetic variations prone to human leukemia. Understanding of the mechanism of leukemia development in these hereditary syndromes allows us to gain insight into leukemogenesis in general and suggests therapeutic strategies based on these findings.

INFECTIOUS DISEASES - INFECCIONES

TÍTULO / TITLE:    - Necrotizing Tenon’s capsule infection in a lymphopenic Down syndrome patient following strabismus surgery.

REVISTA / JOURNAL:    - J AAPOS. 2017 Jun 16. pii: S1091-8531(17)30480-9. doi: 10.1016/j.jaapos.2017.06.006.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jaapos.2017.06.006

AUTORES / AUTHORS: - Chang MY; Velez FG;

INSTITUCIÓN / INSTITUTION: - Department of Ophthalmology, Stein Eye Institute, UCLA Medical Center, Los Angeles; Doheny Eye Institute, UCLA Medical Center, Los Angeles; Olive View, UCLA Medical Center, Los Angeles; Department of Pathology and Laboratory Medicine, David   velez@jsei.ucla.edu

RESUMEN / SUMMARY: - Periocular infection is a rare complication of strabismus surgery. We describe a case of necrotizing Tenon’s capsule infection after uncomplicated strabismus surgery in a boy with Down syndrome and blepharitis. Pathologic diagnosis was severe acute necrotizing inflammation with Gram positive coccal forms. Resolution of infection occurred after surgical debridement and intravenous and topical antibiotics. Work-up revealed lymphopenia related to Down syndrome. Patients with Down syndrome may have risk factors for postoperative infection including blepharitis and immunologic abnormalities.

TÍTULO / TITLE:    - Early increased density of cyclooxygenase-2 (COX-2) immunoreactive neurons in Down syndrome.

REVISTA / JOURNAL:    - Folia Neuropathol. 2017;55(2):154-160. doi: 10.5114/fn.2017.68582.

Enlace a la Editora de la Revista http://dx.doi.org/10.5114/fn.2017.68582

AUTORES / AUTHORS: - Mulet M et al

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Neuroinflammation is one of the hallmarks of Alzheimer’s disease. One of the enzymes involved in neuroinflammation, even in early stages of the disease, is COX-2, an inducible cyclooxygenase responsible for the generation of eicosanoids and for the generation of free radicals. Individuals with Down syndrome develop Alzheimer’s disease early in life. Previous studies pointed to the possible overexpression of COX-2 and correlated it to brain regions affected by the disease. We analysed the COX-2 expression levels in individuals with Down syndrome and in young, adult and old mice of the Ts65Dn mouse model for Down syndrome. We have observed an overexpression of COX-2 in both, Down syndrome individuals and mice. Importantly, mice already presented an overexpression of COX-2 at postnatal day 30, before neurodegeneration begins; which suggests that neuroinflammation may underlie the posterior neurodegeneration observed in individuals with Down syndrome and in Ts65Dn mice and could be a factor for the premature appearance of Alzheimer’s disease.

TÍTULO / TITLE:    - Developmental expression and dysregulation of miR-146a and miR-155 in Down’s syndrome and mouse models of Down’s syndrome and Alzheimer’s disease.

REVISTA / JOURNAL:    - Curr Alzheimer Res. 2017 Jul 6. doi: 10.2174/1567205014666170706112701.

Enlace a la Editora de la Revista http://dx.doi.org/10.2174/1567205014666170706112701

AUTORES / AUTHORS: - Arena A; et al

INSTITUCIÓN / INSTITUTION: - Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Netherlands.  

RESUMEN / SUMMARY: - miR-146a and miR-155 are key regulators of the innate immune response. We hypothesized that an inflammation-mediated dysregulation of these miRNAs may occur in patients with Down syndrome (DS) and Alzheimer’s disease (AD). The miRNA expression patterns were investigated by in situ hybridization in developing hippocampus from controls, patients with DS and in adults with AD pathology (DS and sporadic AD; sAD). quantitative real-time PCR was employed to evaluate the miRNA levels in the hippocampus of sAD and in mouse models of DS and AD. Both miRNAs were expressed in prenatal human hippocampus. In DS we detected increased miR-146a expression in reactive astrocytes. Increased expression of miR-146a was found in the hippocampus of sAD and negatively correlated with its target IRAK-1. APP/PS1 mice showed a significant increase in the expression of both miRNAs at 11-13 months of age as compared to WT and mice at 3 months. A negative correlation between miR-146a levels and its target TRAF6 was observed in both Ts65Dn and APP/PS1 mice. These findings suggest a possible involvement of miR-146a and miR-155 in brain development and neurodegeneration. In particular, we provide evidence of a dysregulation of these two immunomodulatory miRNAs in AD with a potential therapeutical implication, deserving further investigation.

TÍTULO / TITLE:    - CRISPR/Cas9-Directed Reassignment of the GATA1 Initiation Codon in K562 Cells to Recapitulate AML in Down Syndrome.

REVISTA / JOURNAL:    - Mol Ther Nucleic Acids. 2017 Jun 16;7:288-298. doi: 10.1016/j.omtn.2017.04.009. Epub 2017 Apr 13.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.omtn.2017.04.009

AUTORES / AUTHORS: - Bloh KM; Kmiec EB;

INSTITUCIÓN / INSTITUTION: - Gene Editing Institute, Helen F. Graham Cancer Center & Research Institute, Christiana Care Health Services, Inc., Newark, DE 19713, USA   eric.b.kmiec@christianacare.org

RESUMEN / SUMMARY: - Using a CRISPR/Cas9 system, we have reengineered a translational start site in the GATA1 gene in K562 cells. This mutation accounts largely for the onset of myeloid leukemia in Down syndrome (ML-DS). For this reengineering, we utilized CRISPR/Cas9 to generate mammalian cell lines that express truncated versions of the Gata1s protein similar to that seen in ML-DS, as determined by analyzing specific genetic alterations resulting from CRISPR/Cas9 cleavage. During this work, 73 cell lines were clonally expanded, with allelic variance analyzed. Using Tracking of Indels by DEcomposition (TIDE) and Sanger sequencing, we defined the DNA sequence and variations within each allele. We found significant heterogeneity between alleles in the same clonally expanded cell, as well as among alleles from other clonal expansions. Our data demonstrate and highlight the importance of the randomness of resection promoted by non-homologous end joining after CRISPR/Cas9 cleavage in cells undergoing genetic reengineering. Such heterogeneity must be fully characterized to predict altered functionality inside target tissues and to accurately interpret the associated phenotype. Our data suggest that in cases where the objective is to rearrange specific nucleotides to redirect gene expression in human cells, it is imperative to analyze genetic composition at the individual allelic level.

MOLECULAR BIOLOGY/BIOCHEMISTRY - BIOLOGÍA MOLECULAR/BIOQUÍMICA

TÍTULO / TITLE:    - Amniotic Fluid Angiogenic and Inflammatory Factor Profiling in Foetal Down Syndrome.

REVISTA / JOURNAL:    - Fetal Diagn Ther. 2017 Jul 15. doi: 10.1159/000478260.

Enlace a la Editora de la Revista http://dx.doi.org/10.1159/000478260

AUTORES / AUTHORS: - Zbucka-Kretowska M; et al.

INSTITUCIÓN / INSTITUTION: - Department of Reproduction and Gynaecological Endocrinology, Medical University of Bialystok, Bialystok, Poland.  

RESUMEN / SUMMARY: - OBJECTIVES: Angiogenic factors are proteins that can potentially be related to certain foetal chromosomal abnormalities. The goal of this study was to determine the concentrations of 60 angiogenic factors in the amniotic fluid of women carrying foetuses with Down syndrome (DS). METHODS: After analysis of the karyotyping results, for the purpose of this study, we chose 12 women with foetal DS. For the control group, we selected 12 healthy patients with uncomplicated pregnancies (15-18 weeks of gestation) who delivered healthy newborns at term. To assess the concentrations of proteins in the amniotic fluid, we used a protein macroarray, which enabled the simultaneous determination of 60 angiogenic factors per sample. RESULTS: In the amniotic fluid of women with foetal DS compared to patients with healthy foetuses, we reported significant decreases in the concentrations of 14 angiogenic factors, including leptin, angiopoietin 1 (ANG-1), angiostatin, epidermal growth factor (EGF), interleukin 1-beta (IL-1b), interleukin 4 (IL-4), interleukin 12p40 (IL-12p40), monocyte chemotactic protein 2 (MCP-2), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-9 (MMP-9), platelet endothelial cell adhesion molecule 1 (PECAM-1), transforming growth factor alpha (TGF alpha), vascular endothelial growth factor 2 (VEGFR2), and vascular endothelial growth factor 3 (VEGFR3). CONCLUSIONS: Based on our findings, we hypothesise that angiogenic factors may play roles in the pathogenesis of DS. Defining the factors’ potential as biochemical factors of DS requires further investigation in a larger group of patients.

NEUROBIOLOGY - NEUROBIOLOGÍA

TÍTULO / TITLE:    - Aging rather than aneuploidy affects monoamine neurotransmitters in brain regions of Down syndrome mouse models.

REVISTA / JOURNAL:    - Neurobiol Dis. 2017 Sep;105:235-244. doi: 10.1016/j.nbd.2017.06.007. Epub 2017 Jun 15.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.nbd.2017.06.007

AUTORES / AUTHORS: - Dekker AD; De Deyn PP; et al.

INSTITUCIÓN / INSTITUTION: - Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Univers   p.p.de.deyn@umcg.nl

RESUMEN / SUMMARY: - Altered concentrations of monoamine neurotransmitters and metabolites have been repeatedly found in people with Down syndrome (DS, trisomy 21). Because of the limited availability of human post-mortem tissue, DS mouse models are of great interest to study these changes and the underlying neurobiological mechanisms. Although previous studies have shown the potential of Ts65Dn mice - the most widely used mouse model of DS - to model noradrenergic changes, a comprehensive monoaminergic characterization in multiple brain regions has not been performed so far. Here, we used RP-HPLC with electrochemical detection to quantify (nor)adrenergic (NA, adrenaline and MHPG), dopaminergic (DA, HVA and DOPAC), and serotonergic compounds (tryptophan, 5-HT and 5-HIAA) in ten regionally dissected brain regions of Ts65Dn mice, as well as in Dp1Tyb mice - a novel DS mouse model. Comparing young adult aneuploid mice (2.5-5.5months) with their euploid WT littermates did not reveal generalized monoaminergic dysregulation, indicating that the genetic overload in these mice barely affected the absolute concentrations at this age. Moreover, we studied the effect of aging in Ts65Dn mice: comparing aged animals (12-13months) with their younger counterparts revealed a large number of significant changes. In general, the (nor)adrenergic system appeared to be reduced, while serotonergic compounds were increased with aging. Dopaminergic alterations were less consistent. These overall patterns appeared to be relatively similar for Ts65Dn and WT mice, though more observed changes were regarded significant for WT mice. Similar human post-mortem studies are necessary to validate the monoaminergic construct validity of the Ts65Dn and Dp1Typ mouse models.

TÍTULO / TITLE:    - Neuroanatomical alterations and synaptic plasticity impairment in the perirhinal cortex of the Ts65Dn mouse model of Down syndrome.

REVISTA / JOURNAL:    - Neurobiol Dis. 2017 Jun 23;106:89-100. doi: 10.1016/j.nbd.2017.06.017.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.nbd.2017.06.017

AUTORES / AUTHORS: - Roncace V; Bartesaghi R; et al.

INSTITUCIÓN / INSTITUTION: - Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.   renata.bartesaghi@unibo.it

RESUMEN / SUMMARY: - Down syndrome (DS), a genetic condition due to triplication of Chromosome 21, is characterized by numerous neurodevelopmental alterations and intellectual disability. Individuals with DS and DS mouse models are impaired in several memory domains, including hippocampus-dependent declarative (spatial, in rodents) memory and visual recognition memory, a form of memory in which the perirhinal cortex (PRC) plays a fundamental role. The anatomo-functional substrates of hippocampus-dependent memory impairment have been largely elucidated in the Ts65Dn mouse model of DS. In contrast, there is a lack of corresponding information regarding visual recognition memory. Therefore, we deemed it of interest to examine at both an anatomical and functional level the PRC of Ts65Dn mice. We found that the PRC of adult (1.5-3.5month-old) Ts65Dn mice exhibited diffused hypocellularity and neurons with a reduced spine density. No difference between Ts65Dn and euploid mice was detected in the abundance of glutamatergic and GABAergic terminals. We examined brain slices for long-term potentiation (LTP), a form of synaptic plasticity involved in long-term memory. Theta burst stimulation of intracortical fibers was used in order to elicit LTP in the superficial layers of the PRC. We found that in trisomic slices LTP had a similar time-course but a reduced magnitude in comparison with euploid slices. While exposure to the GABAA receptor antagonist picrotoxin had no effect on LTP magnitude, exposure to the GABAB receptor antagonist CGP55845 caused an increase in LTP magnitude that became even larger than in euploid slices. Western blot analysis showed increased levels of the G-protein-activated inwardly rectifying K+ channel 2 (GIRK2) in the PRC of Ts65Dn mice, consistent with triplication of the gene coding for GIRK2. This suggests that the reduced magnitude of LTP may be caused by GIRK2-dependent exaggerated GABAB receptor-mediated inhibition. Results provide novel evidence for anatomo-functio

TÍTULO / TITLE:    - Decreasing the Expression of GABAA alpha5 Subunit-Containing Receptors Partially Improves Cognitive, Electrophysiological, and Morphological Hippocampal Defects in the Ts65Dn Model of Down Syndrome.

REVISTA / JOURNAL:    - Mol Neurobiol. 2017 Jul 17. doi: 10.1007/s12035-017-0675-3.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s12035-017-0675-3

AUTORES / AUTHORS: - Vidal V; Martinez-Cue C

INSTITUCIÓN / INSTITUTION: - Departamento de Fisiologia y Farmacologia, Facultad de Medicina, Universidad deCantabria, Santander, España.   martinec@unican.es

RESUMEN / SUMMARY: - Trisomy 21 or Down syndrome (DS) is the most common cause of intellectual disability of a genetic origin. The Ts65Dn (TS) mouse, which is the most commonly used and best-characterized mouse model of DS, displays many of the cognitive, neuromorphological, and biochemical anomalies that are found in the human condition. One of the mechanisms that have been proposed to be responsible for the cognitive deficits in this mouse model is impaired GABA-mediated inhibition. Because of the well-known modulatory role of GABAA alpha5 subunit-containing receptors in cognitive processes, these receptors are considered to be potential targets for improving the intellectual disability in DS. The chronic administration of GABAA alpha5-negative allosteric modulators has been shown to be procognitive without anxiogenic or proconvulsant side effects. In the present study, we use a genetic approach to evaluate the contribution of GABAA alpha5 subunit-containing receptors to the cognitive, electrophysiological, and neuromorphological deficits in TS mice. We show that reducing the expression of GABAA alpha5 receptors by deleting one or two copies of the Gabra5 gene in TS mice partially ameliorated the cognitive impairments, improved long-term potentiation, enhanced neural differentiation and maturation, and normalized the density of the GABAergic synapse markers. Reducing the gene dosage of Gabra5 in TS mice did not induce motor alterations and anxiety or affect the viability of the mice. Our results provide further evidence of the role of GABAA alpha5 receptor-mediated inhibition in cognitive impairment in the TS mouse model of DS.

TÍTULO / TITLE:    - Molecular Mechanism Underlying Abnormal Differentiation of Neural Progenitor Cells in the Developing Down Syndrome Brain.

REVISTA / JOURNAL:    - Yakugaku Zasshi. 2017;137(7):795-800. doi: 10.1248/yakushi.16-00236-1.

Enlace a la Editora de la Revista http://dx.doi.org/10.1248/yakushi.16-00236-1

AUTORES / AUTHORS: - Kurabayashi N; Sanada K

INSTITUCIÓN / INSTITUTION: - Molecular Genetics Research Laboratory, Graduate School of Science, The University of Tokyo.  

RESUMEN / SUMMARY: - wn syndrome (DS) is caused by trisomy for human chromosome 21. Individuals with DS commonly exhibit mental retardation, which is associated with abnormal brain development. In the neocortex of the DS brain, the density of neurons is markedly reduced, whereas that of astrocytes is increased. Similar to abnormalities seen in DS brains, mouse models of DS show deficits in brain development, and neural progenitor cells that give rise to neurons and glia show dysregulation in their differentiation. These suggest that the dysregulation of progenitor fate choices contributes to alterations in the numbers of neurons and astrocytes in the DS brain. Nevertheless, the molecular basis underlying these defects remains largely unknown. We showed that the overexpression of two human chromosome 21 genes, DYRK1A and DSCR1, contributes to suppressed neuronal differentiation of progenitors in the Ts1Cje mouse model of DS. In addition, the effect of DYRK1A and DSCR1 overexpression on neuronal differentiation is mediated by excessive attenuation of the transcription factor NFATc. Additionally, we demonstrated that an increased dosage of DYRK1A contributes to elevated potential of Ts1Cje progenitors to differentiate into astrocytes and enhanced astrogliogenesis in the Ts1Cje neocortex. Further, we linked the increased dosage of DYRK1A to dysregulation of STAT, a transcription factor critical for astrogliogenesis. Together, our studies identify critical pathways responsible for the proper differentiation of neural progenitors into neurons and astrocytes, with direct implications for the anomalies in brain development observed in DS.

TÍTULO / TITLE:    - Comprehensive Analyses of Molecules with Altered Expression in the Brain of a Mouse Model of Down Syndrome for Identification of Pharmacotherapeutic Targets.

REVISTA / JOURNAL:    - Yakugaku Zasshi. 2017;137(7):807-810. doi: 10.1248/yakushi.16-00236-3.

Enlace a la Editora de la Revista http://dx.doi.org/10.1248/yakushi.16-00236-3

AUTORES / AUTHORS: - Ishihara K;

INSTITUCIÓN / INSTITUTION: - Department of Pathological Biochemistry, Division of Pathological Sciences, Kyoto Pharmaceutical University.  

RESUMEN / SUMMARY: - Down syndrome, caused by the triplication of human chromosome 21, is the most frequent genetic cause of mental retardation. Mice with a segmental trisomy for mouse chromosome 16, which is orthologous to human chromosome 21, exhibit abnormalities similar to those in individuals with Down syndrome and therefore offer the opportunity for a genotype-phenotype correlation. In the current review, I present several mouse lines with trisomic regions of various lengths and discuss their usefulness for elucidating the mechanisms underlying Down syndrome-associated developmental cognitive disabilities. In addition, our recent comprehensive study attempting to identify molecules with disturbed expression in the brain of a mouse model of Down syndrome in order to develop a pharmacologic therapy for Down syndrome is described.

TÍTULO / TITLE:    - Early increased density of cyclooxygenase-2 (COX-2) immunoreactive neurons in Down syndrome.

REVISTA / JOURNAL:    - Folia Neuropathol. 2017;55(2):154-160. doi: 10.5114/fn.2017.68582.

Enlace a la Editora de la Revista Folia Neuropathol. 2017;55(2):154-160. doi: 10.5114/fn.2017.68582.

AUTORES / AUTHORS: - Mulet M et al

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - Neuroinflammation is one of the hallmarks of Alzheimer’s disease. One of the enzymes involved in neuroinflammation, even in early stages of the disease, is COX-2, an inducible cyclooxygenase responsible for the generation of eicosanoids and for the generation of free radicals. Individuals with Down syndrome develop Alzheimer’s disease early in life. Previous studies pointed to the possible overexpression of COX-2 and correlated it to brain regions affected by the disease. We analysed the COX-2 expression levels in individuals with Down syndrome and in young, adult and old mice of the Ts65Dn mouse model for Down syndrome. We have observed an overexpression of COX-2 in both, Down syndrome individuals and mice. Importantly, mice already presented an overexpression of COX-2 at postnatal day 30, before neurodegeneration begins; which suggests that neuroinflammation may underlie the posterior neurodegeneration observed in individuals with Down syndrome and in Ts65Dn mice and could be a factor for the premature appearance of Alzheimer’s disease.

TÍTULO / TITLE:    - Knockdown of Myo-Inositol Transporter SMIT1 Normalizes Cholinergic and Glutamatergic Function in an Immortalized Cell Line Established from the Cerebral Cortex of a Trisomy 16 Fetal Mouse, an Animal M

REVISTA / JOURNAL:    - Neurotox Res. 2017 Jul 10. doi: 10.1007/s12640-017-9775-0.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s12640-017-9775-0

AUTORES / AUTHORS: - Cardenas AM; et al

INSTITUCIÓN / INSTITUTION: - Centro Interdisciplinario de Neurociencia de Valparaiso, Facultad de Ciencias, Universidad de Valparaiso, Valparaiso, Chile.  

RESUMEN / SUMMARY: - The Na+/myo-inositol cotransporter (SMIT1) is overexpressed in human Down syndrome (DS) and in trisomy 16 fetal mice (Ts16), an animal model of the human condition. SMIT1 overexpression determines increased levels of intracellular myo-inositol, a precursor of phophoinositide synthesis. SMIT1 is overexpressed in CTb cells, an immortalized cell line established from the cerebral cortex of a Ts16 mouse fetus. CTb cells exhibit impaired cytosolic Ca2+ signals in response to glutamatergic and cholinergic stimuli (increased amplitude and delayed time-dependent kinetics in the decay post-stimulation), compared to our CNh cell line, derived from the cerebral cortex of a euploid animal. Considering the role of myo-inositol in intracellular signaling, we normalized SMIT1 expression in CTb cells using specific mRNA antisenses. Forty-eight hours post-transfection, SMIT1 levels in CTb cells reached values comparable to those of CNh cells. At this time, decay kinetics of Ca2+ signals induced by either glutamate, nicotine, or muscarine were accelerated in transfected CTb cells, to values similar to those of CNh cells. The amplitude of glutamate-induced cytosolic Ca2+ signals in CTb cells was also normalized. The results suggest that SMIT1 overexpression contributes to abnormal cholinergic and glutamatergic Ca2+ signals in the trisomic condition, and knockdown of DS-related genes in our Ts16-derived cell line could constitute a relevant tool to study DS-related neuronal dysfunction.

TÍTULO / TITLE:    - Deleterious Effects of Chronic Folate Deficiency in the Ts65Dn Mouse Model of Down Syndrome.

REVISTA / JOURNAL:    - Front Cell Neurosci. 2017 Jun 9;11:161. doi: 10.3389/fncel.2017.00161. eCollection 2017.

Enlace a la Editora de la Revista http://dx.doi.org/10.3389/fncel.2017.00161

AUTORES / AUTHORS: - Helm S; et al

INSTITUCIÓN / INSTITUTION: - Natural Science Division, Pepperdine UniversityMalibu, CA, United States.  

RESUMEN / SUMMARY: - Folate is an important B vitamin naturally found in the human diet and plays a critical role in methylation of nucleic acids. Indeed, abnormalities in this major epigenetic mechanism play a pivotal role in the pathogenesis of cognitive deficit and intellectual disability in humans. The most common cause of cognitive dysfunction in children is Down syndrome (DS). Since folate deficiency is very common among the pediatric population, we questioned whether chronic folate deficiency (CFD) exacerbates cognitive dysfunction in a mouse model of DS. To test this, adult Ts65Dn mice and their disomic littermates were chronically fed a diet free of folic acid while preventing endogenous production of folate in the digestive tract for a period of 8 weeks. Our results show that the Ts65Dn mouse model of DS was significantly more vulnerable to CFD in terms of plasma homocysteine and N5-methyltetrahydrofolate (5-MTHF) levels. Importantly, these changes were linked to degenerative alterations in hippocampal dendritic morphology and impaired nest building behavior in Ts65Dn mice. Based on our results, a rigorous examination of folate intake and its metabolism in individuals with DS is warranted.

NEUROLOGY - NEUROLOGÍA

TÍTULO / TITLE:    - Normalizing the gene dosage of Dyrk1A in a mouse model of Down syndrome rescues several Alzheimer’s disease phenotypes.

REVISTA / JOURNAL:    - Neurobiol Dis. 2017 Jun 21;106:76-88. doi: 10.1016/j.nbd.2017.06.010.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.nbd.2017.06.010

AUTORES / AUTHORS: - Garcia-Cerro S; Rueda N; Vidal V; Lantigua S; Martinez-Cue C

INSTITUCIÓN / INSTITUTION: - Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Santander, España.   martinec@unican.es

RESUMEN / SUMMARY: - The intellectual disability that characterizes Down syndrome (DS) is primarily caused by prenatal changes in central nervous system growth and differentiation. However, in later life stages, the cognitive abilities of DS individuals progressively decline due to accelerated aging and the development of Alzheimer’s disease (AD) neuropathology. The AD neuropathology in DS has been related to the overexpression of several genes encoded by Hsa21 including DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), which encodes a protein kinase that performs crucial functions in the regulation of multiple signaling pathways that contribute to normal brain development and adult brain physiology. Studies performed in vitro and in vivo in animal models overexpressing this gene have demonstrated that the DYRK1A gene also plays a crucial role in several neurodegenerative processes found in DS. The Ts65Dn (TS) mouse bears a partial triplication of several Hsa21 orthologous genes, including Dyrk1A, and replicates many DS-like abnormalities, including age-dependent cognitive decline, cholinergic neuron degeneration, increased levels of APP and Abeta, and tau hyperphosphorylation. To use a more direct approach to evaluate the role of the gene dosage of Dyrk1A on the neurodegenerative profile of this model, TS mice were crossed with Dyrk1A KO mice to obtain mice with a triplication of a segment of Mmu16 that includes this gene, mice that are trisomic for the same genes but only carry two copies of Dyrk1A, euploid mice with a normal Dyrk1A dosage, and CO animals with a single copy of Dyrk1A. Normalizing the gene dosage of Dyrk1A in the TS mouse rescued the density of senescent cells in the cingulate cortex, hippocampus and septum, prevented cholinergic neuron degeneration, and reduced App expression in the hippocampus, Abeta load in the cortex and hippocampus, the expression of phosphorylated tau at the Ser202 residue in the hippocampus and cerebellum and the levels

TÍTULO / TITLE:    - Down syndrome and Moyamoya disease: unusual cause of stroke.

REVISTA / JOURNAL:    - British Medical J (BMJ). Free access to the article (immediately). http://bmj.com/search.dtl

Enlace a la Editora de la Revista http://dx.doi.org/10.1136/bcr-2017-219894

AUTORES / AUTHORS: - Tavares Bello C; et al

INSTITUCIÓN / INSTITUTION: - Centro Hospitalar de Lisboa Ocidental-Hospital de Egas Moniz, Lisbon, Portugal.  

RESUMEN / SUMMARY: - Centro Hospitalar de Lisboa Ocidental-Hospital de Egas Moniz, Lisbon, Portugal. SUMMARY: Down syndrome is a frequent clinical entity, being considered one of the most frequent chromosomal aberrations. It is characterised by a typical clinical phenotype and is associated with a heterogeneous group of organ and system-specific abnormalities. The cardiovascular system is commonly affected and if so, it may be associated with an increased morbidity and mortality. Cerebrovascular events in patients with Down syndrome are multifactorial, being possibly related to congenital heart disease, vascular malformations and traditional cardiovascular risk factors. Moyamoya disease is a rare chronic occlusive vascular disease causing stenosis of the distal portion of the internal carotid artery, which has been associated with Down syndrome. The authors report the case of a 26-year-old woman with Down syndrome who presented with an acute stroke secondary to Moyamoya disease. The case is noteworthy for the rarity of this clinicopathological entity, and serves as a reminder for the possible association between these two conditions.

OPHTALMOLOGY - OFTALMOLOGÍA

TÍTULO / TITLE:    - Impairments in the Visual Processing of Global Biological Motion Cues in Down Syndrome.

REVISTA / JOURNAL:    - Perception. 2017 Jan 1:301006617718716. doi: 10.1177/0301006617718716.

Enlace a la Editora de la Revista http://dx.doi.org/10.1177/0301006617718716

AUTORES / AUTHORS: - Riddell H; et al

INSTITUCIÓN / INSTITUTION: - University of Munster, Germany.  

RESUMEN / SUMMARY: - Down syndrome (DS) is one of the most common chromosomal disorders and is often associated with a number of motor and cognitive impairments. Little research has been dedicated to investigating the perceptual abilities of individuals with DS. The visual processing of biological motion has been shown to be impaired in DS. It has been proposed that these impairments may stem from an inability to process the global patterns of full-body motion produced by a moving actor; however, this has not been explicitly investigated. We tested groups of participants with and without DS on a task requiring the visual discrimination of point-light walkers from spatially scrambled versions of point-light walkers. Participants with DS demonstrated poorer performance and slower reaction times on the task than healthy controls. From these results, we conclude that biological motion processing is impaired in DS and that this deficit is related to an inability to integrate global configural cues. In a second experiment, individuals with DS were able to discriminate the direction in which laterally translating walkers moved, suggesting that the global motion processing deficit observed in Experiment 1 is specific to biological motion recognition and does not generalise to other types of global motion.

TÍTULO / TITLE:    - Surgical, medical and developmental outcomes in patients with Down syndrome and cataracts.

REVISTA / JOURNAL:    - SAGE Open Med. 2017 Jun 19;5:2050312117715583. doi: 10.1177/2050312117715583. eCollection 2017.

Enlace a la Editora de la Revista http://dx.doi.org/10.1177_2050312117715583

AUTORES / AUTHORS: - Santoro SL; et al.

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

RESUMEN / SUMMARY: - BACKGROUND: Individuals with Down syndrome have an increased risk for congenital cataracts, but descriptions of surgical, medical and developmental outcomes are sparse. MATERIALS AND METHODS: Retrospective review of medical charts of patients with Down syndrome with visits to Cincinnati Children’s Hospital from 1988 to 2013 was performed. A case series of five patients with Down syndrome and cataracts is presented. A total of 47 patients with Down syndrome without cataracts were used as a developmental control. Developmental quotients were compared using an independent-sample, unequal variance t-test. RESULTS: Post-operative cataract complication rates ranged from 20% to 60%. Visual outcomes were varied; significant associations between complication rate and visual outcome were not found. Developmental quotients did not show an association with number of complications, but were lower for children with Down syndrome with cataracts requiring surgery compared to children with Down syndrome without cataracts. CONCLUSION: In children with Down syndrome and congenital cataract, surgical intervention has risk for post-operative complications. Further investigation is needed to determine if there is an association between surgical complications and visual or developmental outcomes.

TÍTULO / TITLE:    - Necrotizing Tenon’s capsule infection in a lymphopenic Down syndrome patient following strabismus surgery.

REVISTA / JOURNAL:    - J AAPOS. 2017 Jun 16. pii: S1091-8531(17)30480-9. doi: 10.1016/j.jaapos.2017.06.006.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jaapos.2017.06.006

AUTORES / AUTHORS: - Chang MY; Velez FG;

INSTITUCIÓN / INSTITUTION: - Department of Ophthalmology, Stein Eye Institute, UCLA Medical Center, Los Angeles; Doheny Eye Institute, UCLA Medical Center, Los Angeles; Olive View, UCLA Medical Center, Los Angeles; Department of Pathology and Laboratory Medicine, David   velez@jsei.ucla.edu

RESUMEN / SUMMARY: - Periocular infection is a rare complication of strabismus surgery. We describe a case of necrotizing Tenon’s capsule infection after uncomplicated strabismus surgery in a boy with Down syndrome and blepharitis. Pathologic diagnosis was severe acute necrotizing inflammation with Gram positive coccal forms. Resolution of infection occurred after surgical debridement and intravenous and topical antibiotics. Work-up revealed lymphopenia related to Down syndrome. Patients with Down syndrome may have risk factors for postoperative infection including blepharitis and immunologic abnormalities.

ORTHOPEDICS - ORTOPEDÍA

TÍTULO / TITLE:    - Bone health in Down syndrome.

REVISTA / JOURNAL:    - Med Clin (Barc). 2017 Jul 21;149(2):78-82. doi: 10.1016/j.medcli.2017.04.020. Epub 2017 May 30.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.medcli.2017.04.020

AUTORES / AUTHORS: - Garcia-Hoyos M; Valero C; et al

INSTITUCIÓN / INSTITUTION: - Departamento de Medicina Interna, Hospital Universitario Marques de Valdecilla, Universidad de Cantabria, Instituto de Investigacion Sanitaria Valdecilla (IDIVAL), Santander, España.   mirvdc@humv.es

RESUMEN / SUMMARY: - Patients with Down syndrome have a number of risk factors that theoretically could predispose them to osteoporosis, such as early aging, development disorders, reduced physical activity, limited sun exposure, frequent comorbidities and use of drug therapies which could affect bone metabolism. In addition, the bone mass of these people may be affected by their anthropometric and body composition peculiarities. In general terms, studies in adults with Down syndrome reported that these people have lower areal bone mineral density (g/cm2) than the general population. However, most of them have not taken the smaller bone size of people with Down syndrome into account. In fact, when body mineral density is adjusted by bone size and we obtain volumetric body mineral density (g/cm3), the difference between both populations disappears. On the other hand, although people with Down syndrome have risk factor of hypovitaminosis D, the results of studies regarding 25(OH)D in this population are not clear. Likewise, the studies about biochemical bone markers or the prevalence of fractures are not conclusive.

TÍTULO / TITLE:    - Bone mineral density in adults with Down syndrome.

REVISTA / JOURNAL:    - Osteoporos Int. 2017 Jul 6. doi: 10.1007/s00198-017-4133-x.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s00198-017-4133-x

AUTORES / AUTHORS: - Carfi A et al.

INSTITUCIÓN / INSTITUTION: - Department of Gerontology, Neurosciences, Head and Neck and Orthopedics, Catholic University of the Sacred Heart, Largo Agostino Gemelli, 8, 00168, Rome, Italy.  

RESUMEN / SUMMARY: - This study analyzed data of bone mineral density (BMD) from a large cohort of adults with Down syndrome (DS). BMD was found to decrease with age more rapidly in these subjects than in the general population, exposing adults with DS to an increased risk of osteoporosis and bone fracture. INTRODUCTION: Down syndrome (DS) in adulthood presents with a high prevalence of osteoporosis. However, in DS, bone mineral density (BMD) can be underestimated due to short stature. Furthermore, the rate of age-related decline in BMD and its association with gender in DS has been rarely evaluated or compared with the general population. The present study is aimed at assessing the variation of BMD with age and gender in a sample of adults with DS and to compare these data with those of the general population, after adjusting for anthropometric differences. METHODS: Adults with DS, aged 18 or older, were assessed dual-energy-X-ray-absorptiometry (DXA) at the femoral neck and at the lumbar spine. They were compared with the general population enrolled in the National Health and Nutrition Examination Survey (NHANES) 2009-2010 dataset. Bone mineral apparent density (BMAD) was calculated for each individual. RESULTS: DXA was evaluated in 234 subjects with DS (mean age 36.93 +/- 11.83 years, ranging from 20 to 69 years; 50.4% females). In the lumbar spine both mean BMD (DS 0.880 +/- 0.141 vs. NHANES 1.062 +/- 0.167, p < 0.001) and BMAD (DS 0.138 +/- 0.020 vs. NHANES 0.152 +/- 0.020, p < 0.001) were significantly lower in the DS sample than in the NAHNES cohort. The same trend was observed at the femoral neck in both BMD (DS 0.658 +/- 0.128 vs. NHANES 0.835 +/- 0.137, p < 0.001) and BMAD (DS 0.151 +/- 0.030 vs. NHANES 0.159 +/- 0.028, p<0.001). Age was associated with lower femoral neck BMAD in both samples; importantly, this association was significantly stronger in the DS sample. In the lumbar spine region, no significant association between BMAD and age could be observed in both samples.

PHYSIOTHERAPY - FISIOTERAPIA

TÍTULO / TITLE:    - Wii-based exercise program to improve physical fitness, motor proficiency and functional mobility in adults with Down syndrome.

REVISTA / JOURNAL:    - J Intellect Disabil Res. 2017 Aug;61(8):755-765. doi: 10.1111/jir.12384. Epub 2017 Jun 6.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jir.12384

AUTORES / AUTHORS: - Silva V; et al.

INSTITUCIÓN / INSTITUTION: - Polytechnic Institute of Porto, Health School, Porto, Portugal.  

RESUMEN / SUMMARY: - BACKGROUND: People with Down syndrome (DS) usually display reduced physical fitness (aerobic capacity, muscle strength and abnormal body composition), motor proficiency impairments (balance and postural control) and physical functional limitations. Exergames can be an appealing alternative to enhance exercise engagement and compliance, whilst improving physical fitness and motor function. This study aims to analyse the effects of a Wii-based exercise program on physical fitness, functional mobility and motor proficiency of adults with DS. METHODS: Twenty-seven adults with DS were randomly allocated to an experimental group (Wii; n = 14) or control group (n = 13). Participants in the experimental group completed a 2-month Wii-based exercise program, with three 1-h sessions per week that included training games for aerobic endurance, balance and isometric strength. Participants completed assessments regarding anthropometric measures, physical fitness, functional mobility and motor proficiency. RESULTS: Mixed ANOVA analysis showed a significant group by time interaction for aerobic endurance, explosive leg power and flexibility. Independent samples t-test for change scores indicated significant between-group differences favouring the experimental group regarding speed of limb movement, trunk strength and functional mobility, as well as a trend towards significance on body weight. Mann-Whitney’s U test for change scores demonstrated between-group differences favouring the experimental group for visceral fat as well as running speed and agility. Large within-group effect sizes were observed for explosive leg power (d = 1.691), body weight (d = 1.281), functional mobility (d = 1.218), aerobic endurance (d = 1.020), speed of limb movement (d = 0.867) and flexibility (d = 0.818) in the experimental group. CONCLUSIONS: Our findings suggest that Wii-based exercise can be an effective tool to improve physical fitness, functional mobility and motor proficiency of adults with DS

TÍTULO / TITLE:    - Hand span influences optimal grip span in adolescents with Down syndrome

REVISTA / JOURNAL:    - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=28627199&dopt=Abstrac

AUTORES / AUTHORS: - Casajus JA;

INSTITUCIÓN / INSTITUTION: -   joseant@unizar.es

RESUMEN / SUMMARY: - INTRODUCTION: The hand grip strength test provides useful and reliable information about overall health. Different studies have investigated the optimal grip span for determining maximal hand grip strength in different populations such as adults, adolescents and children without disabilities. OBJECTIVE: To ascertain whether there is an optimal grip span for determining maximal hand grip strength in adolescents with Down syndrome (DS). METHODS: Twenty-seven right-handed youths with DS (seven females) aged 15.5 +/- 3.6 years were evaluated in this methodological study. Each hand was randomly tested on ten times using five different grip spans, allowing one-minute rest between attempts. The hand span was measured from the tip of the thumb to the tip of the small finger with the hand widely opened. To confirm the usefulness of the optimal grip span, a new group of 15 adolescents with DS were recruited. RESULTS: An optimal grip span was identified for the dominant hand in adolescents with DS. The equation relating grip span as a function of dominant hand span in this group is formulated as follows: y = 0.342x - 1.161 cm (r = 0.63, p < 0.05). In the case of non-dominant hand, a tendency towards a linear association (p = 0.058) was found; the equation is formulated as follows: y = 0,210x + 1.324 cm. CONCLUSION: It is important to standardize the procedure and increase reliability when measuring hand grip strength in DS population. The values stated in this study are recommended to assess hand grip strength in adolescents with Down syndrome.

TÍTULO / TITLE:    - Oxidant production and SOD1 protein expression in single skeletal myofibers from Down syndrome mice.

REVISTA / JOURNAL:    - Oxidant production and SOD1 protein expression in single skeletal myofibers from Down syndrome mice.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.redox.2017.07.003

AUTORES / AUTHORS: - Cowley PM; DeRuisseau KC;

INSTITUCIÓN / INSTITUTION: - Syracuse University, Department of Exercise Science, Syracuse, NY, USA.   kcderuis@syr.edu

RESUMEN / SUMMARY: - Down syndrome (DS) is a genetic condition caused by the triplication of chromosome 21. Persons with DS exhibit pronounced muscle weakness, which also occurs in the Ts65Dn mouse model of DS. Oxidative stress is thought to be an underlying factor in the development of DS-related pathologies including muscle dysfunction. High-levels of oxidative stress have been attributed to triplication and elevated expression of superoxide dismutase 1 (SOD1); a gene located on chromosome 21. The elevated expression of SOD1 is postulated to increase production of hydrogen peroxide and cause oxidative injury and cell death. However, it is unknown whether SOD1 protein expression is associated with greater oxidant production in skeletal muscle from Ts65Dn mice. Thus, our objective was to assess levels of SOD1 expression and oxidant production in skeletal myofibers from the flexor digitorum brevis obtained from Ts65Dn and control mice. Measurements of oxidant production were obtained from myofibers loaded with 2’,7’-dichlorodihydrofluorescein diacetate (DCFH2-DA) in the basal state and following 15min of stimulated unloaded contraction. Ts65Dn myofibers exhibited a significant decrease in basal DCF emissions (p < 0.05) that was associated with an approximate 3-fold increase in SOD1 (p < 0.05). DCF emissions were not affected by stimulating contraction of Ts65Dn or wild-type myofibers (p > 0.05). Myofibers from Ts65Dn mice tended to be smaller and myonuclear domain was lower (p < 0.05). In summary, myofibers from Ts65Dn mice exhibited decreased basal DCF emissions that were coupled with elevated protein expression of SOD1. Stimulated contraction in isolated myofibers did not affect DCF emissions in either group. These findings suggest the skeletal muscle dysfunction in the adult Ts65Dn mouse is not associated with skeletal muscle oxidative stress.

TÍTULO / TITLE:    - Hting in Children and Adults With Down Syndrome: Developmental Delay or Specific Features? andwri

REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2017 Jul;122(4):342-353. doi: 10.1352/1944-7558-122.4.342.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-122.4.342

AUTORES / AUTHORS: - Tsao R;

INSTITUCIÓN / INSTITUTION: - Raphaele Tsao, Aix Marseille University.  

RESUMEN / SUMMARY: - While there is a long history and tradition of behavioral research on basic motor skills in Down syndrome (DS), there has been only limited research on handwriting ability. We analyzed the spatiotemporal features of handwriting produced by children and adults with DS (n = 24), and compared their productions with those of comparison groups matched for developmental (n = 24) or chronological (n = 24) age. Results indicated that the participants with DS performed an alphabet letter-writing task just as efficiently as the children of the same developmental age, in terms of the length, duration and speed of their handwriting, and the number and duration of their pauses. Our study highlights a substantial delay in the stages of writing acquisition.

PRENATAL DIAGNOSIS - DIAGNÓSTICO

TÍTULO / TITLE:    - Analysis of Down syndrome failed to be diagnosed after prenatal screening: A multicenter study.

REVISTA / JOURNAL:    - Medicine (Baltimore). 2017 Jun;96(24):e7166. doi: 10.1097/MD.0000000000007166.

Enlace a la Editora de la Revista http://dx.doi.org/10.1097/MD.0000000000007166

AUTORES / AUTHORS: - Jiang T; et al.

INSTITUCIÓN / INSTITUTION: - aObstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing bSuzhou Municipal Hospital affiliated to Nanjing Medical University, Suzhou cChangzhou Woman and Children Health Hospital Affiliated to Nanjing Medical Un  

RESUMEN / SUMMARY: - To analyze the characters of Down syndrome (DS) who failed to be diagnosed after prenatal screening and hope to be able to improve the programs of prenatal screening and reduce the missed diagnosis of DS. In this multicenter study, we collected the missed cases from 3 prenatal diagnosis centers and analyzed their characters. A total of 126 DS babies failed to be diagnosed after prenatal screening. Their mothers accepted the prenatal screening in second trimester. We collected the mothers’ blood and detected the levels of alpha-fetoprotein (AFP) and the free beta subunit of human chorionic gonadotropin (fbetahCG) by time-resolved fluoroimmunoassay. The values were also presented as multiples of the median (MoM) and determined the risk of carrying a fetus with DS by Wallace LifeCycle Elipse analysis software. Compared with normal control group, the level of fbetahCG and hCG MoM were dramatically increased, while AFP and AFP MoM were decreased. The area under the receiver-operating-characteristic curve of trisomy 21 was 0.8387 for hCG-MoM and AFP-MoM testing. The sensitivity, specificity, positive predictive value, and negative predictive value were 84.6%, 74.8%, 75.4%, and 83.6%, respectively. Meanwhile, the prediction mode was “0.39957 + 1.90897HCG-MOM -3.32713AFP-MOM”. It was worthwhile noting that the risk of 65.9% DS missed diagnosis group were higher than 1/1000, 92.9% higher than 1/3000. However, 72.5% cases in normal control group were lower than 1/3000. Only 9.2% mothers would be higher than the value of risk in 1/1000. The prediction mode of hCG MoM and AFP MoM might be able to help us reduce the missed diagnosis. It is also necessary to adjust more reasonable range of noninvasive prenatal testing with further clinical researches.

TÍTULO / TITLE:    - Age-based differences in the predictive accuracy of a one-size-fits-all risk-cutoff value in prenatal integrated screening for Down syndrome.

REVISTA / JOURNAL:    - Prenat Diagn. 2017 Jun 27. doi: 10.1002/pd.5101.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/pd.5101

AUTORES / AUTHORS: - Yan J; et al.

INSTITUCIÓN / INSTITUTION: - H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA, USA.  

RESUMEN / SUMMARY: - OBJECTIVE: The objective of this study is to assess variation in detection and false positive rates and adverse pregnancy outcomes across different age groups when a one-size-fits-all risk-cutoff value, such as 1/270, is used in integrated screening for Down syndrome. METHOD: A Monte Carlo simulation was utilized to estimate the detection and false positive rates as well as adverse pregnancy outcomes. RESULTS: Using a one-size-fits-all risk-cutoff value, such as 1/270, can result in considerably high variations in detection and false positive rates across maternal ages and lead to a higher than the minimum possible total number of adverse outcomes. CONCLUSION: Our findings indicate that the one-size-fits-all risk-cutoff value of 1/270, commonly used in DS screening, should be revisited and alternative (possibly age-based) cutoff values and strategies should be considered. © 2017 John Wiley& Sons, Ltd.

TÍTULO / TITLE:    - Abortion of Fetus with Down’s Syndrome: India Joins the Worldwide Controversy Surrounding Abortion Laws.

REVISTA / JOURNAL:    - Sci Eng Ethics. 2017 Jun 12. doi: 10.1007/s11948-017-9926-y.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s11948-017-9926-y

AUTORES / AUTHORS: - Taneja A; Menezes RG;

INSTITUCIÓN / INSTITUTION: - Forensic Medicine Division, Department of Pathology, College of Medicine, King Fahd Hospital of the University, University of Dammam, Dammam, Saudi Arabia.   mangalore971@yahoo.co.in

RESUMEN / SUMMARY: - Abortion continues to be a moral and ethical dilemma in medicine. While abortions in general have always faced social stigmas, the abortion of fetuses with Down’s syndrome in particular remains the subject of debate across the globe. In India, under the Medical Termination of Pregnancy Act, abortion is legal under prescribed circumstances only till 20 weeks of gestation. Laws for abortion after 20 week of gestation are ill defined. In a recent ruling of the Supreme Court in India, a woman was denied the right to abortion of her 26 week old fetus. With this ruling, India has joined the rest of the world in the debate surrounding abortion laws and the ethics of abortion.

TÍTULO / TITLE:    - Patients’ Knowledge of Prenatal Screening for Trisomy 21.

REVISTA / JOURNAL:    - J Genet Couns. 2017 Jul 14. doi: 10.1007/s10897-017-0126-3.

Enlace a la Editora de la Revista http://dx.doi.org/10.1007/s10897-017-0126-3

AUTORES / AUTHORS: - Sheinis M; Selk A et al

INSTITUCIÓN / INSTITUTION: - Department of Obstetrics & Gynaecology, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.   amanda.selk@utoronto.ca

RESUMEN / SUMMARY: - This study’s objective was to assess the knowledge of prenatal screening for Trisomy 21 in pregnant women in one institution in Canada. A cross-sectional survey measuring demographics, knowledge of screening, and health literacy, was administered to pregnant women. Of the 135 women who completed the survey, 74% had adequate knowledge of Trisomy 21 and associated screening procedures. Twenty-eight point one percent of women did not receive any counseling. Overall, 29.5% of women did not know that the screening test was optional and 10.2% of women underwent screening prior to having been counseled. Multigravidity (p < 0.05) and prior counseling (p < 0.001) were positively correlated with knowledge while first language other than English (p < 0.001) was negatively correlated with knowledge. Given these findings, an effort needs to be made on the part of health care providers to increase counseling rates to 100%, stressing the optional nature of the test to attain true informed consent.

TÍTULO / TITLE:    - Enhanced First Trimester Screening for Trisomy 21 with Contingent Cell-Free Fetal DNA: A Comparative Performance and Cost Analysis.

REVISTA / JOURNAL:    - J Obstet Gynaecol Can. 2017 Jun 14. pii: S1701-2163(16)39844-9. doi: 10.1016/j.jogc.2017.01.025.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jogc.2017.01.025

AUTORES / AUTHORS: - Huang T; et al

INSTITUCIÓN / INSTITUTION: - Genetics Program, North York General Hospital, Toronto, ON; Better Outcomes Registry& Network (BORN) Ontario, Ottawa, ON; The Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON.   tianhua.huang@nygh.on.ca

RESUMEN / SUMMARY: - OBJECTIVE: Prenatal screening for trisomy 21 is a standard of care. Emerging cell-free fetal DNA (cffDNA) technologies can improve screening performance, but they are expensive. This study was conducted to propose a contingent screening model that would incorporate cffDNA technology, would remain affordable, and could be applied equitably in a publically funded system. METHODS: Using performance and cost parameters from published literature, four prenatal screening strategies were compared. Scenario 1 modelled integrated prenatal screening (first trimester nuchal translucency and biochemical markers from both the first and second trimesters) with no cffDNA. Scenarios 2 and 3 modelled first trimester combined screening (FTS) and “enhanced FTS” (adding serum placental growth factor and alpha fetoprotein to FTS), respectively, with contingent cffDNA following a positive result. Scenario 4 modelled cffDNA as the primary screening test. RESULTS: Scenario 1 provides a known detection rate (DR) of 88%, with a false positive rate (FPR) of 3.3%. Scenarios 2 and 3 result in a DR of 94% and overall FPR of 0.59% and 0.33%, respectively, comparable to the DR of 96% and FPR of 0.1% with primary cffDNA (assuming the published test failure rate of 3%). The total cost, cost per woman screened, and cost per case of trisomy 21 detected were lower with scenario 3 (enhanced FTS with contingent cffDNA) compared with primary cffDNA or scenario 2 (FTS with contingent cffDNA). CONCLUSION: Enhanced FTS with contingent cffDNA following a positive result provides a similar performance to that of primary cffDNA at a substantially lower cost.

TÍTULO / TITLE:    - Strong impact of ethnicity on effectiveness of the first trimester maternal serum screen of fetal Down syndrome.

REVISTA / JOURNAL:    - J Matern Fetal Neonatal Med. 2017 Aug 2:1-5. doi: 10.1080/14767058.2017.1358264.

Enlace a la Editora de la Revista http://dx.doi.org/10.1080/14767058.2017.1358264

AUTORES / AUTHORS: - Lerthiranwong T; et al

INSTITUCIÓN / INSTITUTION: - a Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University , Chiang Mai , Thailand.  

RESUMEN / SUMMARY: - OBJECTIVES: The objective of this study is to compare the effectiveness of first-trimester maternal serum screening (MSS) for fetal Down syndrome among Thai women between the method using Caucasian reference ranges with racial factor correction (CRR-RC) and that using Thai reference ranges (TRR). METHODS: A prospective database of MSS was accessed. The levels of PAPP-A and beta-hCG were calculated to determine their MoMs (multiple of medians) by two methods: (1) CRR-RC for Asian women and (2) TRR. The MoMs from both methods were used to determine the fetal risk. RESULTS: Of 24,885 women including 36 fetuses with Down syndrome, the detection rates were significantly higher with TRR when compared with CRR-RC, 77.8 and 63.9%, respectively, p < .001. Additionally, the false-positive rates were significantly lower with TRR when compared to CRR-RC (7.5 versus 12.5%, respectively, p < .001) Conclusions: The effectiveness of MSS was much better by using our own reference ranges rather than the method of racial factor correction. The important insight is that ethnicity strongly impacts on the effectiveness that cannot be completely corrected by ethnic factor. MSS derived by the CRR-RC in other regions should be interpreted with high precaution, especially where the biophysical characteristics of the women are much different from Caucasian population

TÍTULO / TITLE:    - Impact of prenatal screening on the prevalence of Down syndrome in Slovenia.

REVISTA / JOURNAL:    - PLoS One. 2017 Jun 30;12(6):e0180348. doi: 10.1371/journal.pone.0180348. eCollection 2017.

Enlace a la Editora de la Revista http://dx.doi.org/10.1371/journal.pone.0180348

AUTORES / AUTHORS: - Rudolf G; et al.

INSTITUCIÓN / INSTITUTION: - Clinical Institute of Medical Genetics (CIMG), University Medical Centre Ljubljana, Ljubljana, Slovenia.  

RESUMEN / SUMMARY: - OBJECTIVES: To evaluate the impact of prenatal screening and genetic testing for trisomy 21 (T21) on the prevalence of T21 in Slovenia. DESIGN AND SETTING: Data about all prenatally and postnatally confirmed cases of T21 in Slovenia between 1981 and 2012 were collected retrospectively from all genetic laboratories in Slovenia. The expected number of babies with T21 according to maternal age was calculated. MAIN OUTCOME MEASURES: The primary outcomes measures were number of fetuses and newborn infants with T21 diagnosed prenatally and postnatally and the impact of advances in screening and genetic diagnostics on the prevalence of newborns with T21 in Slovenia. RESULTS: Despite a significantly increased mean maternal age from 25.4 years in year 1981 to 30.3 years in year 2012 the prevalence of newborn infants with T21 was 0.51 per 1000 births compared to 0.55 per 1000 births, respectively. The prevalence of prenatally diagnosed cases increased from 0.03 per 1000 births to 2.06 per 1000. The detection rate of T21 in year 2012 was 78,9%. The total number of prenatal invasive procedures (chorionic villous sampling and amniocenteses) carried out during that period was rising until 2002, since when it is stable at around 7%. CONCLUSION: The advancement and implementation of screening tests and prenatal diagnostic procedures in Slovenia caused an important improvement in the efficiency of the prenatal detection of T21.

TÍTULO / TITLE:    - Systematic review and meta-analysis of non-invasive prenatal DNA testing for trisomy 21: implications for implementation in China.

REVISTA / JOURNAL:    - Prenat Diagn. 2017 Jul 7. doi: 10.1002/pd.5111.

Enlace a la Editora de la Revista http://dx.doi.org/10.1002/pd.5111

AUTORES / AUTHORS: - Jin J et al

INSTITUCIÓN / INSTITUTION: - School of Public Health, Fudan University, Shanghai, China. Key Laboratory of Health Technology Assessment, National Health and Family Planning Committee (Fudan University), Shanghai, China.  

RESUMEN / SUMMARY: - OBJECTIVES: To systematically review clinical validation studies of massive parallel sequencing (MPS) technology in prenatal screening for trisomy 21 and to explore the potential implementation strategies in China compared with those in developing countries. METHODS: Searches of the Cochrane Library, Medline, EMBASE, Web of Science, Biosis Previews, and three major Chinese databases were performed to identify all the peer-reviewed articles published between 1 January 2011 and 15 October 2016. We also reviewed and discussed the potential challenges and risks in the future promotion of MPS technology in China compared with those in developing countries. RESULTS: The weighted pooled sensitivity and specificity of MPS technology for the prenatal detection of trisomy 21 were 99.7% (95% CI 98.3-99.9%) and 100.0% (95% CI 99.9-100.0%), respectively, based on a meta-analysis of 44 included studies. An additional meta-analysis was conducted based on the 25 included studies that were performed in medical/genetic sequencing institutions in mainland China, showing a weighted pooled sensitivity and specificity of MPS technology as 99.5% (95% CI 98.7-99.8%) and 100% (95% CI 99.9-100%), respectively. CONCLUSION: MPS technology offers effective screening performance for trisomy 21 but should be cautiously promoted due to its clinical limitations and challenges that stem from the ethics and business aspects. © 2017 John Wiley& Sons, Ltd.

PSYCHIATRY - PSIQUIATRÍA

TÍTULO / TITLE:    - A cross-sectional analysis of executive function in Down syndrome from 2 to 35 years.

REVISTA / JOURNAL:    - J Intellect Disabil Res. 2017 Jul 20. doi: 10.1111/jir.12396.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jir.12396

AUTORES / AUTHORS: - Loveall SJ; et al

INSTITUCIÓN / INSTITUTION: - Department of Communication Sciences and Disorders, University of Mississippi, Oxford, MS, USA. Department of Psychology, University of Alabama, Tuscaloosa, AL, USA.  

RESUMEN / SUMMARY: - BACKGROUND: Previous research has indicated a unique profile of executive function (EF) in children and adolescents with Down syndrome (DS). However, there is a paucity of research on EF in adults with DS. This study aimed to gain a broader understanding of strengths and weaknesses in EF in DS from 2 to 35 years. METHOD: Parents of 112 individuals with DS between 2 and 35 years participated in this study. Parents either completed the Behaviour Rating Inventory of Executive Function - for individuals 6+ years - or the Behaviour Rating Inventory of Executive Function Preschool Version - for children 2-5 years. RESULTS: Results suggest not only overall difficulties but also patterns of strength and weakness within EF for individuals with DS. For the 2 to 5-year-old group, emotional control and shift were relative strengths, planning/organisation and inhibit were intermediate skills, and working memory was a relative weakness. For the 6 to 18-year-old group, emotional control and organisation of materials were relative strengths, inhibit and initiate were intermediate skills, and working memory, monitor, planning/organisation, and shift were relative weaknesses. Most abilities were consistent from 2 to 18 years, except shift, which decreased in preadolescence before beginning to recover in adolescence. Across the full age range (2-35 years), composite scores indicated quadratic trends in inhibit, working memory, and planning/organisation, and a cubic trend in shift, with EF abilities generally declining in middle childhood before recovering in adulthood. CONCLUSIONS: This study extends previous research on EF in DS by providing an initial description of EF profiles across the lifespan. More longitudinal and behavioural research is needed to further characterise the development of EF in DS.

TÍTULO / TITLE:    - BACKGROUND: Previous research has indicated a unique profile of executive function (EF) in children and adolescents with Down syndrome (DS). However, there is a paucity of research on EF in adults wit

REVISTA / JOURNAL:    - Child Adolesc Psychiatry Ment Health. 2017 Jul 24;11:40. doi: 10.1186/s13034-017-0177-0. eCollection

Enlace a la Editora de la Revista http://dx.doi.org/10.1186/s13034-017-0177-0

AUTORES / AUTHORS: - Del Cole CG; et al.

INSTITUCIÓN / INSTITUTION: - Laboratorio Interdisciplinar de Neurociencias Clinicas (LiNC), Departamento de Psiquiatria, Universidade Federal de Sao Paulo, Edificio de Pesquisas II - UNIFESP, Rua Pedro de Toledo, 669-3 degrees andar fundos, Vila Clementino, Sao Paulo,  

RESUMEN / SUMMARY: - BACKGROUND: Adaptive behavior can be impaired in different neurodevelopmental disorders and may be influenced by confounding factors, such as intelligence quotient (IQ) and socioeconomic classification. Our main objective was to verify whether adaptive behavior profiles differ in three conditions-Williams Beuren syndrome (WBS), Down syndrome (DS), and autism spectrum disorder (ASD), as compared with healthy controls (HC) and with each other. Although the literature points towards each disorder having a characteristic profile, no study has compared profiles to establish the specificity of each one. A secondary objective was to explore potential interactions between the conditions and socioeconomic status, and whether this had any effect on adaptive behavior profiles. METHODS: One hundred and five adolescents were included in the study. All adolescents underwent the following evaluations: the Vineland Adaptive Behavior Scale (VABS), the Wechsler Intelligence Scale for Children (WISC), and the Brazilian Economic Classification Criteria. RESULTS: Our results demonstrated that the WBS group performed better than the DS group in the communication domain, beta = -15.08, t(3.45), p = .005, and better than the ASD group in the socialization domain, beta = 8.92, t(-2.08), p = .013. The DS group also performed better than the ASD group in socialization, beta = 16.98, t(-2.32), p = .024. IQ was an important confounding factor, and socioeconomic status had an important effect on the adaptive behavior of all groups. CONCLUSIONS: There is a heterogeneity regarding adaptive behavior profiles in WBS, DS, and ASD. These data are important to better design specific strategies related to the health and social care of each particular group.

TÍTULO / TITLE:    - Repetitive Behaviours and Restricted Interests in Individuals with Down Syndrome-One Way of Managing Their World?

REVISTA / JOURNAL:    - Brain Sci. 2017 Jun 15;7(6). pii: E66. doi: 10.3390/brainsci7060066.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/brainsci7060066

AUTORES / AUTHORS: - Glenn S;

INSTITUCIÓN / INSTITUTION: - School of Natural Sciences and Psychology, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool L3 3AF, UK   s.m.glenn@ljmu.ac.uk

RESUMEN / SUMMARY: - This paper argues that the repetitive behaviour and restrictive interests (RBRI) displayed by individuals with Down syndrome have mostly positive functions. However, as research has developed from interests in Obsessional Compulsive Disorder or Autistic Spectrum Disorder, unfortunately a view has arisen that RBRI in individuals with Down syndrome are also likely to be pathological. This is particularly the case in adults. The paper reviews: (a) measures employed and the perspectives that have been used; (b) the development in typically developing individuals, those with Down syndrome, and those with other conditions associated with intellectual disability; (c) positive and possible negative effects of RBRI; and (d) the need for more research. The conclusion is that, for their level of development, RBRI are helpful for most individuals with Down syndrome.

QUALITY OF LIFE - CALIDAD DE VIDA

TÍTULO / TITLE:    - Caregiver-Reported Quality of Life in Youth with Down Syndrome.

REVISTA / JOURNAL:    - J Pediatr. 2017 Jul 24. pii: S0022-3476(17)30923-X. doi: 10.1016/j.jpeds.2017.06.073.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jpeds.2017.06.073

AUTORES / AUTHORS: - Xanthopoulos MS; et al.

INSTITUCIÓN / INSTITUTION: - Department of Child and Adolescent Psychiatry and Behavioral Sciences, Children’s Hospital of Philadelphia, Philadelphia, PA.   xanthop@email.chop.edu

RESUMEN / SUMMARY: - OBJECTIVES: To describe caregiver-reported quality of life (QOL) in youth with Down syndrome (DS) and to examine the role of obesity on QOL. STUDY DESIGN: Caregivers of youth with and without DS aged 10 through 20 years completed questionnaires examining QOL (Pediatric Quality of Life Questionnaire) and weight-related QOL (Impact of Weight on Quality of Life - Kids). Age- and sex-specific z scores were generated for body mass index. Obesity was defined as a body mass index >/=95th percentile for age and sex. RESULTS: Caregiver-reported Total QOL, Physical Health, and Psychosocial Health summary scores were all lower in the DS group compared with the non-DS controls (P < .001). Social and School Functioning were also lower (P < .001), but Emotional Functioning did not differ between DS and non-DS groups (P = .31). Physical Functioning (P = .003) and Total scores (P = .03) differed between youth without DS with and without obesity, but no differences were reported between youth with DS with and without obesity. On the Impact of Weight on Quality of Life - Kids, caregivers of youth with DS reported greater Body Esteem (P = .020) and Social Life scores (P = .03) than caregivers of non-DS youth. Caregivers of youth with obesity, regardless of DS status, reported significantly lower weight-specific QOL scores than caregivers of youth without obesity. CONCLUSION: Caregivers reported lower QOL in youth with DS compared with youth without DS with the exception of emotional functioning. Obesity influences most domains of weight-related QOL in youth with and without DS; therefore, providers should address weight concerns in youth with obesity even in the presence of DS. CLINICAL TRIAL REGISTRATION: NCT01821300.

TÍTULO / TITLE:    - Parenting children with down syndrome: An analysis of parenting styles, parenting dimensions, and parental stress.

REVISTA / JOURNAL:    - Res Dev Disabil. 2017 Sep;68:9-19. doi: 10.1016/j.ridd.2017.06.010. Epub 2017 Jul 7.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ridd.2017.06.010

AUTORES / AUTHORS: - Phillips BA; et al

INSTITUCIÓN / INSTITUTION: - Ouachita Baptist University, Arkadelphia, AR, 71998, USA.   phillipsa@obu.edu

RESUMEN / SUMMARY: - BACKGROUND: Effective parenting is vital for a child’s development. Although much work has been conducted on parenting typically developing children, little work has examined parenting children with Down syndrome. AIMS: The purpose of the current study was to compare the parenting styles and dimensions in mothers of children with DS and mothers of TD children. METHODS AND PROCEDURES: Thirty-five mothers of children with DS and 47 mothers of TD children completed questionnaires about parenting, parental stress, child behavior problems, and child executive function. OUTCOMES AND RESULTS: We found that mothers of children with DS use an authoritative parenting style less and a permissive parenting style more than mothers of TD children. Additionally, we found that mothers of children with DS use reasoning/induction and verbal hostility less and ignoring misbehavior more than mothers of TD children. All of these differences, except for those of reasoning/induction, were at least partially accounted for by the higher levels of parental stress in the DS group. CONCLUSIONS AND IMPLICATIONS: Parenting interventions should be focused on reducing parental stress and training mothers to parent under stress in an effort to improve parenting techniques, which would, in theory, improve long-term child outcomes for children with DS.

TÍTULO / TITLE:    - Distress and everyday problems in Dutch mothers and fathers of young adolescents with Down syndrome.

REVISTA / JOURNAL:    - Res Dev Disabil. 2017 Aug;67:19-27. doi: 10.1016/j.ridd.2017.05.005. Epub 2017 Jun 12.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ridd.2017.05.005

AUTORES / AUTHORS: - Marchal JP, van Oers HA, Maurice-Stam H, Grootenhuis, MA, van Trotsenburg P, Haverman L.

INSTITUCIÓN / INSTITUTION: - Academic Medical Center, University of Amsterdam, Psychosocial Department, Emma Children’s Hospital, Amsterdam Public Health research institute, Post Box 22660, 1100 DD, Amsterdam, The Netherlands; Academic Medical Center, University of Ams   j.p.marchal@amc.uva.nl

RESUMEN / SUMMARY: - BACKGROUND: To provide targeted support to parents of children with DS, knowledge of their distress and everyday problems is crucial. For this purpose, psychosocial screening instruments can be a valuable addition to routine clinical practice. AIMS: To determine differences on a psychosocial screener concerning distress and everyday problems in parents of young adolescents (YAs) with DS versus control parents and in mothers of YAs with DS versus fathers. METHODS AND PROCEDURES: We compared outcomes of the Distress Thermometer for Parents in 76 mothers and 44 fathers of 11-13-year-olds with DS versus 64 mothers and 52 fathers of age-matched children without DS (comparing mothers and fathers separately). Additionally, we compared mothers and fathers within 34 parent couples of YAs with DS. OUTCOMES AND RESULTS: Clinical distress was not more frequent than in control parents. Mothers further did not report more everyday problems and only differed from their controls on one problem domain and some problem items. Fathers, however, reported more problems than their controls across most domains and wished to talk to a professional about their situation more frequently. Outcomes in mothers and fathers within parent couples did not differ significantly. CONCLUSIONS AND IMPLICATIONS: This is one of few studies to report on the use of psychosocial screening instruments in parents of children with DS. Our results suggested that attention for fathers of YAs with DS is required. Psychosocial screening instruments that inquire about specific problems and the wish for referral can play an important role in achieving this.

TÍTULO / TITLE:    - Social Inclusion of Children With Down Syndrome: Jewish and Muslim Mothers’ Knowledge, Attitudes, Beliefs, and Behavioral Intentions.

REVISTA / JOURNAL:    - J Pediatr Nurs. 2017 Jul - Aug;35:50-56. doi: 10.1016/j.pedn.2017.02.035. Epub 2017 Mar 9.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.pedn.2017.02.035

AUTORES / AUTHORS: - Barnoy S; et al Itzhaki M;

INSTITUCIÓN / INSTITUTION: - Nursing Department, School of Health Professions, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.   itzhakim@post.tau.ac.il

RESUMEN / SUMMARY: - PURPOSE: The current study examined mothers’ knowledge, beliefs, attitudes, and intention to socially integrate children with Down syndrome (DS) in the family, with children without disabilities and school system. DESIGN AND METHODS: A questionnaire based on a descriptive, cross-sectional design was administered to Jewish and Muslim mothers. The questionnaire included demographics, knowledge, beliefs, attitudes, and intention to integrate children with DS. Analysis included a regression test of intention to integrate children with DS and a one-way ANOVA for differences between Jewish and Muslim mothers. RESULTS: Nearly all the Jewish mothers (93.7%) and about half the Muslim mothers (52.8%) had performed screening tests for DS during their pregnancy. All mothers displayed low knowledge level about DS. Being Jewish (t=2.89; p=0.005) and holding more positive beliefs (t=3.39; p=0.001) were associated with a higher intention to socially integrate children with DS. Significant positive correlations were found between beliefs and attitudes (r=0.65; p<0.001) and between attitudes and intention to socially integrate children with DS (r=0.39; p<0.001). CONCLUSIONS: This study shows that Jewish and Muslim mothers’ beliefs and attitudes towards social inclusion of children with DS are quite positive and the intention to integrate children with DS in the family, with children without disabilities, and in the mainstream school system is high. However, their level of knowledge about DS is low. PRACTICE IMPLICATIONS: Nurses, as a critical source of information about DS, should develop an ethno-cultural sensitivity to diverse populations in order to influence attitudes and beliefs regarding the social integration of children with DS.

TÍTULO / TITLE:    - A Retrospective, Longitudinal, Claims-Based Comparison of Concomitant Diagnoses Between Individuals with and Without Down Syndrome.

REVISTA / JOURNAL:    - J Manag Care Spec Pharm. 2017 Jul;23(7):761-770. doi: 10.18553/jmcp.2017.23.7.761.

Enlace a la Editora de la Revista http://dx.doi.org/10.18553/jmcp.2017.23.7.761

AUTORES / AUTHORS: - Kong AM;et al.

INSTITUCIÓN / INSTITUTION: - 1 Truven Health Analytics, an IBM Company, Ann Arbor, Michigan.  

RESUMEN / SUMMARY: - BACKGROUND: Individuals with Down syndrome (DS) experience various comorbidities in excess of the prevalence seen among the non-DS population. However, the extent of the excess burden of comorbidities specifically within commercially and publicly insured DS populations aged < 21 years is not currently known. OBJECTIVES: To (a) describe the most common diagnoses among individuals with DS who have either commercial or Medicaid insurance and (b) compare the prevalence of those diagnoses between DS cases and non-DS controls. METHODS: This was a longitudinal, retrospective study using health care claims of commercially insured and Medicaid-insured individuals in the Truven Health MarketScan Databases from 2008 to 2015. Individuals aged < 2, 2-5, 6-11, and 12-20 years with a DS diagnosis (cases; commercial: n = 15,948; Medicaid: n = 11,958) were matched to individuals without DS (controls; commercial: n = 47,844; Medicaid: n = 35,874) using a 1:3 ratio. The annual number of diagnoses was compared between cases and controls within age groups using t-tests, and the prevalence of the most common diagnoses was compared using chi-square tests. RESULTS: Cases in all age groups in both databases had more diagnoses annually than controls (mean =9-17 per year vs. 4-10 per year, P < 0.001), and the number of diagnoses decreased with age for cases and controls. Among the most common case diagnoses were upper respiratory infections (28.9%-59.1% vs. 19.5%-52.9%); suppurative otitis media (25.1%-56.8% vs. 8.7%-51.2%); nutrition/metabolic/developmental symptoms (37.9%-50.4% vs. 7.7%-10.6%); delays in development (22.8%-52.8% vs. 4.1%-10.9%); and general symptoms (35.1%-47.2% vs. 22.1%-37.2%), and the prevalence of each was greater among cases versus controls in all age groups in both databases (P < 0.001). The most common diagnoses among controls included some of the same as among cases, as well as acute pharyngitis (18.7%-31.8% vs. 19.2%-30.5%); allergic rhinitis (19.9%-24.3% vs. 15.3%

TÍTULO / TITLE:    - Repetitive Behaviours and Restricted Interests in Individuals with Down Syndrome-One Way of Managing Their World?

REVISTA / JOURNAL:    - Brain Sci. 2017 Jun 15;7(6). pii: E66. doi: 10.3390/brainsci7060066.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/brainsci7060066

AUTORES / AUTHORS: - Glenn S;

INSTITUCIÓN / INSTITUTION: - School of Natural Sciences and Psychology, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool L3 3AF, UK.   s.m.glenn@ljmu.ac.uk

RESUMEN / SUMMARY: - This paper argues that the repetitive behaviour and restrictive interests (RBRI) displayed by individuals with Down syndrome have mostly positive functions. However, as research has developed from interests in Obsessional Compulsive Disorder or Autistic Spectrum Disorder, unfortunately a view has arisen that RBRI in individuals with Down syndrome are also likely to be pathological. This is particularly the case in adults. The paper reviews: (a) measures employed and the perspectives that have been used; (b) the development in typically developing individuals, those with Down syndrome, and those with other conditions associated with intellectual disability; (c) positive and possible negative effects of RBRI; and (d) the need for more research. The conclusion is that, for their level of development, RBRI are helpful for most individuals with Down syndrome.

RESPIRATORY - RESPIRATORIO

TÍTULO / TITLE:    - Sleep-disordered breathing and cognitive functioning in preschool children with and without Down syndrome.

REVISTA / JOURNAL:    - J Intellect Disabil Res. 2017 Aug;61(8):778-791. doi: 10.1111/jir.12387. Epub 2017 Jun 14.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jir.12387

AUTORES / AUTHORS: - Joyce A; Dimitriou D

INSTITUCIÓN / INSTITUTION: - Centre for Research in Psychology, Behaviour and Achievement, Coventry University, Coventry, UK.  

RESUMEN / SUMMARY: - BACKGROUND: Sleep affects children’s cognitive development, preparedness for school and future academic outcomes. People with Down syndrome (DS) are particularly at risk for sleep-disordered breathing (SDB). To our knowledge, the association between SDB and cognition in preschoolers with DS is unknown. METHODS: We assessed sleep by using cardiorespiratory polygraphy in 22 typically developing (TD) preschoolers and 22 with DS. Cognition was assessed by using the Mullen Scales of Early Learning and behaviour by using the Strengths and Difficulties Questionnaire (SDQ). The MacArthur Communicative Development Inventory (MCDI) measured language level. We predicted that sleep problems would be associated with lower cognitive and behavioural functioning. RESULTS: In TD children, longer sleep duration was associated with higher scores on MCDI expressive language and fewer emotional symptoms such as fear and unhappiness on the SDQ, whilst SDB was associated with increased conduct problems and less prosocial behaviour on the SDQ. Conversely, for children with DS, SDB was associated with increased language understanding and use of actions and gestures on the MCDI. CONCLUSIONS: The findings in the TD group support our hypotheses. We recommend that sleep problems are screened for and treated as even mild SDB may prompt poorer cognition and behaviour. For children with DS, we expect that multiple factors in this complex syndrome mask or mediate the association between sleep and cognitive development and tighter controls are necessary to uncover effects of sleep. We propose longitudinal studies as a necessary tool to assess the precise impact of sleep on cognitive development in accounting for individual differences in DS.

TÍTULO / TITLE:    - Sleep

REVISTA / JOURNAL:    - Children (Basel). 2017 Jun 30;4(7). pii: E55. doi: 10.3390/children4070055.

Enlace a la Editora de la Revista http://dx.doi.org/10.3390/children4070055

AUTORES / AUTHORS: - Fan Z; et al.

INSTITUCIÓN / INSTITUTION: - Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.   zhengfan@med.unc.edu

RESUMEN / SUMMARY: - Patients with Down syndrome (DS) are at risk for both obstructive sleep apnea (OSA) and central sleep apnea (CSA); however, it is unclear how these components evolve as patients age and whether patients are also at risk for hypoventilation. A retrospective review of 144 diagnostic polysomnograms (PSG) in a tertiary care facility over 10 years was conducted. Descriptive data and exploratory correlation analyses were performed. Sleep disordered breathing was common (seen in 78% of patients) with an average apnea-hypopnea index (AHI) = 10. The relative amount of obstructive apnea was positively correlated with age and body mass index (BMI). The relative amount of central sleep apnea was associated with younger age in the very youngest group (0-3 years). Hypoventilation was common occurring in more than 22% of patients and there was a positive correlation between the maximum CO(2) and BMI. Sleep disordered breathing, including hypoventilation, was common in patients with DS. The obstructive component increased significantly with age and BMI, while the central component occurred most in the very young age group. Due to the high risk of hypoventilation, which has not been previously highlighted, it may be helpful to consider therapies to target both apnea and hypoventilation in this population.

TÍTULO / TITLE:    - Success of Tonsillectomy for Obstructive Sleep Apnea in Children With Down Syndrome.

REVISTA / JOURNAL:    - J Clin Sleep Med. 2017 Jul 14. pii: jc-17-00022.

AUTORES / AUTHORS: - Ingram DG et al

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common in children with Down syndrome (DS) and associated with significant morbidity. In the current study we examined polysomnographic outcomes of children with DS who underwent tonsillectomy. METHODS: A retrospective chart review of children with DS who underwent a tonsillectomy between 2009-2015 was performed. All children had either a concurrent adenoidectomy or had previously underwent an adenoidectomy. Children with preoperative and postoperative polysomnograms within 6 months of surgery were included in the analysis. Preoperative OSA severity was categorized by obstructive apnea-hypopnea index (OAHI) as follows: mild = 1.5-4.9 events/h; moderate = 5-9.9 events/h; severe> /= 10 events/h. RESULTS: Seventy-five children with DS met inclusion criteria. The cohort included 41 males and 34 females with mean age of 5.1 years (+/- 3.6 years), range of 0.51-16.60 years. Preoperative OSA severity was as follows, mild = 8/75; moderate = 16/75; severe = 51/75. Cure rates varied depending on definition: 12% for OAHI< 1 event/h and 21% for OAHI< 2 events/h. 48% had residual OAHI< 5 events/h. On postoperative PSG 16/75 saw resolution (OAHI< 2) in OSA; mild = 21/75; moderate = 20/75; severe = 18/75. 48% moderate/severe patients saw conversion to mild or cure. Overall, tonsillectomy resulted in significant improvements in multiple respiratory parameters, including OAHI (OAHI; 21.3 +/- 19.7 to 8.0 +/- 8.1, P< .001), percent sleep time with oxygen saturations < 90% (19.0 +/- 25.0 to 6.1 +/- 10.1, P< .001), and percent sleep time with end-tidal carbon dioxide above 50 mmHg (7.7 +/- 18.0 to 1.8 +/- 6.6, P = .001). Average asleep oxygen saturation was associated with postoperative OSA severity. CONCLUSIONS: Children with DS and OSA who undergo tonsillectomy experience improvements in both respiratory event frequency and gas exchange but approximately half still have moderate to severe residual OSA.

TÍTULO / TITLE:    - Predicting the presence of sleep-disordered breathing in children with Down syndrome.

REVISTA / JOURNAL:    - Sleep Med. 2017 Aug;36:104-108. doi: 10.1016/j.sleep.2017.03.032. Epub 2017 May 31.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.sleep.2017.03.032

AUTORES / AUTHORS: - Nehme J; Katz SL; et al.

INSTITUCIÓN / INSTITUTION: - Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canad   skatz@cheo.on.ca

RESUMEN / SUMMARY: - OBJECTIVE: Sleep-disordered breathing (SDB) is highly prevalent in children with Down syndrome. Given the scarcity of resources and the presence of risk factors for SDB in this population, the objective of this study is to identify the clinical predictors of SDB, which would assist prioritization of children with Down syndrome for SDB evaluation. METHODS: A retrospective cohort study was conducted on children enrolled in the Down syndrome clinic at CHEO who underwent polysomnography in 2004-2014. Total apnea-hypopnea index (AHI) or obstructive AHI (OAHI) > 5 events/hour was considered clinically significant. Associations between SDB and concurrent diagnoses, referral reasons, and sleep symptoms assessed by questionnaire were examined using Pearson’s chi-square test or Fisher’s exact test as appropriate. Univariate and multivariate logistic regression analyses were used to examine the predictors of SDB. RESULTS: SDB was present in 42.9% of 119 children, with its highest prevalence at age 8 years. Symptoms were not significantly associated with AHI > 5 events/hour or OAHI > 5 events/hour. Gastroesophageal reflux was associated with lower odds of OAHI > 5 events/hour on univariate testing (odds ratio 0.16, 95% CI 0.04-0.72; p = 0.02) and multivariate analysis (odds ratio 0.05, 95% CI 0.0006-0.50; p = 0.002). CONCLUSIONS: SDB is highly prevalent at all ages in children with Down syndrome. Symptoms did not predict SDB in this population, although gastroesophageal reflux may mimic SDB, which indicates that clinicians should continue to perform ongoing surveillance for SDB throughout the lifespan of children with Down syndrome.

SURGERY - CIRUGÍA

TÍTULO / TITLE:    - Congenital duodenal and multiple jejunal atresia with malrotation in a patient with Down syndrome.

REVISTA / JOURNAL:    - Congenit Anom (Kyoto). 2017 Jul 4. doi: 10.1111/cga.12236.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/cga.12236

AUTORES / AUTHORS: - Shironomae T, Satomi M; et al

INSTITUCIÓN / INSTITUTION: - Department of Pediatric Surgery, Kanazawa Medical University, Kahoku, Ishikawa, Japan.  

RESUMEN / SUMMARY: -

THERAPEUTICS - TERAPÉUTICA

TÍTULO / TITLE:    - Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome.

REVISTA / JOURNAL:    - Behav Brain Res. 2017 Jul 22. pii: S0166-4328(17)30434-5. doi: 10.1016/j.bbr.2017.07.022.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.bbr.2017.07.022

AUTORES / AUTHORS: - Corrales A; et al. Rueda N;

INSTITUCIÓN / INSTITUTION: - Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, Santander, España.   ruedan@unican.es

RESUMEN / SUMMARY: - Melatonin administered during adulthood induces beneficial effects on cognition and neuroprotection in the Ts65Dn (TS) mouse model of Down syndrome. Here, we investigated the effects of pre- and post-natal melatonin treatment on behavioral and cognitive abnormalities and on several neuromorphological alterations (hypocellularity, neurogenesis impairment and increased oxidative stress) that appear during the early developmental stages in TS mice. Pregnant TS females were orally treated with melatonin or vehicle from the time of conception until the weaning of the offspring, and the pups continued to receive the treatment from weaning until the age of 5 months. Melatonin administered during the pre- and post-natal periods did not improve the cognitive impairment of TS mice as measured by the Morris Water maze or fear conditioning tests. Histological alterations, such as decreased proliferation (Ki67+ cells) and hippocampal hypocellularity (DAPI+ cells), which are typical in TS mice, were not prevented by melatonin. However, melatonin partially regulated brain oxidative stress by modulating the activity of the primary antioxidant enzymes (superoxide dismutase in the cortex and catalase in the cortex and hippocampus) and slightly decreasing the levels of lipid peroxidation in the hippocampus of TS mice. These results show the inability of melatonin to prevent cognitive impairment in TS mice when it is administered at pre- and post-natal stages. Additionally, our findings suggest that to induce pro-cognitive effects in TS mice during the early stages of development, in addition to attenuating oxidative stress, therapies should aim to improve other altered processes, such as hippocampal neurogenesis and/or hypocellularity.

URINARY/RENAL - URINARIO/RENAL

TÍTULO / TITLE:    - Nephro-urological malformations in children with Down syndrome.

REVISTA / JOURNAL:    - Rev Chil Pediatr. 2017 Jun;88(3):431-432. doi: 10.4067/S0370-41062017000300019.

Enlace a la Editora de la Revista http://dx.doi.org/10.4067/S0370-41062017000300019

AUTORES / AUTHORS: - Cavagnaro F;

INSTITUCIÓN / INSTITUTION: - Clinica Alemana de Santiago, Chile.  

RESUMEN / SUMMARY: -

EDUCATION - EDUCACIÓN

TÍTULO / TITLE:    - Assessing pragmatic communication in children with Down syndrome.

REVISTA / JOURNAL:    - J Commun Disord. 2017 Jun 9;68:10-23. doi: 10.1016/j.jcomdis.2017.06.003.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.jcomdis.2017.06.003

AUTORES / AUTHORS: - Smith E; Naess KB; Jarrold C;

INSTITUCIÓN / INSTITUTION: - University of Oslo, Norway.   mailto:k.a.b.nass@uv.uio.no

RESUMEN / SUMMARY: - PURPOSE: Successful communication depends on language content, language form, and language use (pragmatics). Children with Down syndrome (DS) experience communication difficulties, however little is known about their pragmatic profile, particularly during early school years. The purpose of the present study was to explore the nature of pragmatic communication in children with DS. METHOD: Twenty-nine six-year-old children with DS were assessed, in the areas of 1) initiation, 2) scripted language, 3) understanding context and 4) nonverbal communication, as reported by children’s parents via the Children’s Communication Checklist-2 (Bishop, 2003). Additionally, the relationships between pragmatics and measures of vocabulary, nonverbal mental ability and social functioning were explored. RESULTS: Children with DS were impaired relative to norms from typically developing children in all areas of pragmatics. A profile of relative strengths and weaknesses was found in the children with DS; the area of nonverbal communication was significantly stronger, while the area of understanding context was significantly poorer, relative to the other areas of pragmatics assessed in these children. Relationships between areas of pragmatics and other linguistic areas, as well as aspects of vocabulary and social functioning were observed. CONCLUSIONS: By the age of six children with DS experience significantly impaired pragmatic communication, with a clear profile of relative strengths and weaknesses. The study highlights the need to teach children with DS pragmatic skills as a component of communication, alongside language content and form.

TÍTULO / TITLE:    - Parenting children with down syndrome: An analysis of parenting styles, parenting dimensions, and parental stress.

REVISTA / JOURNAL:    - Res Dev Disabil. 2017 Sep;68:9-19. doi: 10.1016/j.ridd.2017.06.010. Epub 2017 Jul 7.

Enlace a la Editora de la Revista http://dx.doi.org/10.1016/j.ridd.2017.06.010

AUTORES / AUTHORS: - Phillips BA; et al

INSTITUCIÓN / INSTITUTION: - Ouachita Baptist University, Arkadelphia, AR, 71998, USA.   phillipsa@obu.edu

RESUMEN / SUMMARY: - BACKGROUND: Effective parenting is vital for a child’s development. Although much work has been conducted on parenting typically developing children, little work has examined parenting children with Down syndrome. AIMS: The purpose of the current study was to compare the parenting styles and dimensions in mothers of children with DS and mothers of TD children. METHODS AND PROCEDURES: Thirty-five mothers of children with DS and 47 mothers of TD children completed questionnaires about parenting, parental stress, child behavior problems, and child executive function. OUTCOMES AND RESULTS: We found that mothers of children with DS use an authoritative parenting style less and a permissive parenting style more than mothers of TD children. Additionally, we found that mothers of children with DS use reasoning/induction and verbal hostility less and ignoring misbehavior more than mothers of TD children. All of these differences, except for those of reasoning/induction, were at least partially accounted for by the higher levels of parental stress in the DS group. CONCLUSIONS AND IMPLICATIONS: Parenting interventions should be focused on reducing parental stress and training mothers to parent under stress in an effort to improve parenting techniques, which would, in theory, improve long-term child outcomes for children with DS.

TÍTULO / TITLE:    - A cross-sectional analysis of executive function in Down syndrome from 2 to 35 years.

REVISTA / JOURNAL:    - J Intellect Disabil Res. 2017 Jul 20. doi: 10.1111/jir.12396.

Enlace a la Editora de la Revista http://dx.doi.org/10.1111/jir.12396

AUTORES / AUTHORS: - Loveall SJ; et al

INSTITUCIÓN / INSTITUTION: - Department of Communication Sciences and Disorders, University of Mississippi, Oxford, MS, USA.  

RESUMEN / SUMMARY: - Previous research has indicated a unique profile of executive function (EF) in children and adolescents with Down syndrome (DS). However, there is a paucity of research on EF in adults with DS. This study aimed to gain a broader understanding of strengths and weaknesses in EF in DS from 2 to 35 years. METHOD: Parents of 112 individuals with DS between 2 and 35 years participated in this study. Parents either completed the Behaviour Rating Inventory of Executive Function - for individuals 6+ years - or the Behaviour Rating Inventory of Executive Function Preschool Version - for children 2-5 years. RESULTS: Results suggest not only overall difficulties but also patterns of strength and weakness within EF for individuals with DS. For the 2 to 5-year-old group, emotional control and shift were relative strengths, planning/organisation and inhibit were intermediate skills, and working memory was a relative weakness. For the 6 to 18-year-old group, emotional control and organisation of materials were relative strengths, inhibit and initiate were intermediate skills, and working memory, monitor, planning/organisation, and shift were relative weaknesses. Most abilities were consistent from 2 to 18 years, except shift, which decreased in preadolescence before beginning to recover in adolescence. Across the full age range (2-35 years), composite scores indicated quadratic trends in inhibit, working memory, and planning/organisation, and a cubic trend in shift, with EF abilities generally declining in middle childhood before recovering in adulthood. CONCLUSIONS: This study extends previous research on EF in DS by providing an initial description of EF profiles across the lifespan. More longitudinal and behavioural research is needed to further characterise the development of EF in DS.

TÍTULO / TITLE:    - Handwriting in Children and Adults With Down Syndrome: Developmental Delay or Specific Features?

REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2017 Jul;122(4):342-353. doi: 10.1352/1944-7558-122.4.342.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-122.4.342

AUTORES / AUTHORS: - Tsao R;

INSTITUCIÓN / INSTITUTION: - Raphaele Tsao, Aix Marseille University.  

RESUMEN / SUMMARY: - While there is a long history and tradition of behavioral research on basic motor skills in Down syndrome (DS), there has been only limited research on handwriting ability. We analyzed the spatiotemporal features of handwriting produced by children and adults with DS (n = 24), and compared their productions with those of comparison groups matched for developmental (n = 24) or chronological (n = 24) age. Results indicated that the participants with DS performed an alphabet letter-writing task just as efficiently as the children of the same developmental age, in terms of the length, duration and speed of their handwriting, and the number and duration of their pauses. Our study highlights a substantial delay in the stages of writing acquisition.

TÍTULO / TITLE:    - The Evaluation of a Personal Narrative Language Intervention for School-Age Children With Down Syndrome.

REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2017 Jul;122(4):310-332. doi: 10.1352/1944-7558-122.4.310.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-122.4.310

AUTORES / AUTHORS: - Finestack L; et al.

INSTITUCIÓN / INSTITUTION: - Lizbeth Finestack, Katy H. O’Brien, Jolene Hyppa-Martin, and Kristen A. Lyrek, University of Minnesota, Speech-Language-Hearing Sciences, Minneapolis, MN.  

RESUMEN / SUMMARY: - The purpose of this study was to evaluate the feasibility of an intervention focused on improving personal narrative skills of school-age children with Down syndrome (DS) using an approach involving visual supports. Four females with DS, ages 10 through 15 years, participated in this multiple baseline across participants single-subject experimental design study. Participants completed 18 intervention sessions that targeted personal narrative goals. Parents completed a survey regarding their perspectives of the intervention. Two participants made small treatment gains in mean length of utterance. One participant had small to medium gains on all macrostructural measures. Parent perspectives were positive. Results support the feasibility of personal narrative interventions for individuals with DS when visual support is provided.

TÍTULO / TITLE:    - A Multi-Method Investigation of Pragmatic Development in Individuals With Down Syndrome.

REVISTA / JOURNAL:    - Am J Intellect Dev Disabil. 2017 Jul;122(4):289-309. doi: 10.1352/1944-7558-122.4.289.

Enlace a la Editora de la Revista http://dx.doi.org/10.1352/1944-7558-122.4.289

AUTORES / AUTHORS: - Lee M; et al.

INSTITUCIÓN / INSTITUTION: -  

RESUMEN / SUMMARY: - This longitudinal study examined pragmatic language in boys and girls with Down syndrome (DS) at up to three time points, using parent report, standardized and direct assessments. We also explored relationships among theory of mind, executive function, nonverbal mental age, receptive and expressive vocabulary, grammatical complexity, and pragmatic competence. Controlling for cognitive and language abilities, children with DS demonstrated greater difficulty than younger typically developing controls on parent report and standardized assessments, but only girls with DS differed on direct assessments. Further, pragmatic skills of individuals with DS developed at a delayed rate relative to controls. Some sex-specific patterns of pragmatic impairments emerged. Theory of mind and executive function both correlated with pragmatic competence. Clinical and theoretical implications are discussed.
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