Down Syndrome Children Research Articles

Methylenetetrahydrofolate reductase polymorphism is not risk factor for Down syndrome in North India.

BACKGROUND:Down syndrome (DS) is the most common cause of mental retardation of genetic etiology with the prevalence rate of 1/700 to 1/1000 live births worldwide. Several polymorphisms in folate/homocysteine metabolism pathways genes have been reported as a risk factor in women for bearing DS child, but very few studies investigated these polymorphisms in DS cases whether there are a risk factor for being DS or not.OBJECTIVE:We have investigated the association of methylenetetrahydrofolate reductase (MTHFR) with the occurrence of DS in Indian population. MTHFR is one of the key regulatory enzymes involved in the metabolic pathway of homocysteine responsible for the reduction of methyltetrahydrofolate. A total of 32 DS cases and 64 age, sex matched controls were genotyped for MTHFR C677T polymorphism by polymerase chain reaction-restriction fragment length polymorphism.RESULTS:The observed genotype frequencies were CC = 0.81; CT = 0.17 and TT = 0.02 in controls and CC = 0.81 and CT = 0.19 in DS cases. Frequency of T allele in DS and controls were 0.09 and 0.1, respectively. Significant difference in the distribution of mutant 677T allele was not observed between DS cases and controls (odds ratio = 0.915; 95% confidence intervals: 0.331-2.53; P = 0.864).CONCLUSION:Results of this study indicate that MTHFR C677T polymorphism is not risk factor for DS.

Infections in children with down syndrome and acute myeloid leukemia: a report from the Canadian infections in AML research group

BackgroundChildren with Down syndrome (DS) are at high risk of infectious toxicity when treated with acute lymphoblastic leukemia chemotherapy protocols optimized in children without DS. Our objective was to determine if children with DS and acute myeloid leukemia (AML) have a different risk of infection when treated with chemotherapy protocols developed for children with DS compared to AML treatment protocols developed for children without DS.MethodsWe conducted a retrospective, population-based cohort study that included DS children ≤ 18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, and treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease or death (whichever occurred first). Trained research associates abstracted all information from each site.ResultsThere were 31 children with DS included; median age was 1.7 (range 0.1-11.1) years. Eleven were treated according to a DS-specific protocol while 20 were treated with non-DS specific protocols. A total of 157 courses of chemotherapy were delivered. Microbiologically documented sterile site infection occurred in 11.9% and 14.3% of DS-specific and non-DS specific AML treatment courses respectively. Sepsis was rare and there were no infection-related deaths. In multiple regression, treatment with a DS-specific protocol was independently associated with a reduction in microbiologically documented sterile site infection (adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42-0.99; P = 0.044), and clinically documented infection (adjusted OR 0.36, 95% CI 0.14-0.91; P = 0.031) but not bacteremia (adjusted OR 0.73, 95% CI 0.44-1.22; P = 0.231).ConclusionsOur study suggests that children with DS do not experience excessive infectious toxicity during treatment for AML compared to children without DS. Incorporation of DS-specific AML treatment protocols is associated with a more favorable infection profile for children with DS-AML.

Assessment of salivary total antioxidant levels and oral health status in children with Down syndrome

Down syndrome (DS) is an autosomal chromosomal disorder caused by trisomy of all or a critical part of chromosome 21. Individuals with DS have high levels of oxidative stress throughout their lifespan. It has been suggested that levels of antioxidants could be altered in response to an infection or disease. To assess the total antioxidant capacity (TAC), nitric oxide (NO), and sialic acid (SA) of saliva in children with DS and its relation to their oral health status. Thirty-four noninstitutionalized children in the age group of 7-12 years having DS formed the study group. The control group consisted of 34 normal, healthy children. The W.H.O. criteria were used for diagnosis and recording of dental caries. Oral hygiene status was assessed using the simplified oral hygiene index. Estimation of TAC, NO, and SA levels in saliva was done. Data obtained were subjected to statistical analysis. In comparison to normal children, DS children showed significantly lower TAC of saliva and significantly higher salivary SA levels. In both groups of children, dental caries was higher in primary dentition when compared to their permanent dentition.

The MTR 2756A>G polymorphism and maternal risk of birth of a child with Down syndrome: a case–control study and a meta-analysis

Methionine synthase (MTR) is required for the conversion of homocysteine (hcy) to methionine in the one-carbon metabolic pathway. Previous studies investigating a common MTR 2756A>G polymorphism as a maternal risk factor for the birth of a child with Down syndrome (DS) are conflicting and limited by small case-control cohorts, and its contribution to circulating hcy levels is still debated. We performed a large case-control study and a meta-analysis of the literature to further address the role of MTR 2756A>G as a maternal risk factor for the birth of a child with DS. 286 mothers of a DS child (MDS) and 305 control mothers of Italian origin were included in the case-control study. Genotyping was performed by means of PCR/RFLP technique. Data on circulating levels of hcy, folates, and vitamin B12 were available for 189 MDS and 194 control mothers. The meta analysis of previous and present data involved a total of 8 studies (1,171 MDS and 1,402 control mothers). Both the case-control study and the meta-analysis showed no association of MTR 2756A>G with the maternal risk of birth of a child with DS (OR=1.15; 95% CI 0.85-1.55, and OR=1.08; 95% CI 0.93-1.25, respectively), even after stratification of the overall data available for the meta-analysis into ethnic groups. No association of the studied polymorphism with circulating levels of hcy, folates, and vitamin B12 was observed. Present data do not support a role for MTR 2756A>G as independent maternal risk factor for a DS birth.

Understanding goals and intentions in low-functioning autism

We investigated ability to understand goals and attribute intentions in the context of two imitation studies in low-functioning, nonverbal children with autism (L-F CWA), a population that is rarely targeted by research in the domain. Down syndrome children (DSC) and typically developing children (TDC) were recruited to form matched comparison groups. In the two sets of simple action demonstrations only contextual indicators of the model's intentions were manipulated. In the Head touch experiment the model activated a button on a toy by pushing it with the forehead, whereas in the Hidden box experiment the model used a ball with a magnet to lift a box out of its container. Both actions were unusual and non-affordant with regards to the objects involved, none of the children in the baseline condition produced them. L-F CWA imitated the experimenter exactly, regardless of the model's intention. TDC showed appreciation of the model's intention by imitating her actions selectively. DSC reproduced only the intentional action as often as they imitated the experimenter exactly. It is concluded that L-F CWA attributed goals to the observed model, but did not show an appreciation of the model's intentions even in these simplified, nonverbal contexts.

The effects of low arched feet on foot rotation during gait in children with Down syndrome.

In children with Down syndrome (DS) hypotonia and ligament laxity are characteristic features which cause a number of orthopaedic issues, such as flat foot. The aim of this study was to determine if children with flat foot are characterised by an accentuated external foot rotation during walking. Fifty-five children with DS and 15 typically developing children recruited as control group were assessed using three-dimensional gait analysis, using an optoelectronic system, force platforms and video recording. Parameters related to foot rotation were identified and calculated and the participants' foot morphology was assessed using the arch index. Data obtained in this study showed that while DS children without flat foot displayed the foot position on the transverse plane globally close to controls during the whole gait cycle, the DS children with flat foot were characterised by higher extra-rotation of the foot in comparison with those without flat foot and controls. Our results suggest that the presence of flatfoot lead the children with DS to extra-rotate their feet more than the children without flat foot. From a clinical point of view, these results could enhance the rehabilitative programmes in DS.

Identification of dysregulated microRNAs in lymphocytes from children with Down syndrome

Given the important roles of miRNAs in post-transcriptional regulation and its implications for the development of immune tissues and cells, characterization of miRNAs promotes us to uncover the molecular mechanisms underlying the pathway of trisomic chromosome 21 that disrupts the disomic genes expression and immunological defects related to Down syndrome (DS). In the present study, we analyzed global changes and chromosome distribution characteristics of miRNAs expression in lymphocytes from children with trisomy 21 by means of the Illumina high-throughput sequencing technology. Two small libraries were constructed using pool RNA of normal and DS children. The results have been further validated by stem-loop quantitative RT-PCR. Comparison between DS and normal profiles revealed that most of identified miRNAs were expressed at similar levels. The chromosome 21 that contributes to the abundantly expressed miRNAs was small, and not all Hsa21-derived miRNAs were over-expressed with ratios significantly ≥1.5 in Down syndrome children lymphocytes. Based on the deep sequencing technology, 108 novel candidate miRNAs have been identified, and 2 of them were derived from human chromosome 21. For the 114 significantly differentially expressed miRNAs, function annotation of target genes indicated that a set of highly abundantly and significantly differentially expressed miRNAs were involved in hematopoietic or lymphoid organ development, thymus development, and T/B cell differentiation and activation. Our results indicated that these abnormally expressed miRNAs might be associated with the mechanisms that trisomy 21 results in dysregulation of disomic genes and involved in the immunological defects seen in DS.

A Review of the Neurological and Neurosurgical Implications of Down Syndrome in Children

Down syndrome is the most commonly encountered chromosomal translation and has been associated with significant congenital abnormalities in various organ systems. Along with classic facial findings, it may involve the gastroenterologic, cardiac, ophthalmologic, endocrine, immunologic, orthopedic, or neurologic systems. With respect to the neurological system, a higher incidence of moyamoya, seizure disorders, strokes, and spinal ligamentous laxity has been described in these children. We have summarized the current available literature with respect to children who have Down syndrome and the varying neurological pathologic entities associated to help health care providers better understand these patients.

Cytogenetic Findings and Risk Factors for Down Syndrome in Punjab

The aim of the present study was to analyse karyotypic pattern, clinical features and factors responsible for the risk of Down syndrome (DS). Chromosomal investigations were done on 114 cases of Down syndrome referred to the Department of Human Genetics, Guru Nanak Dev University, Amritsar. Among 114 cases, 100(87.71%) showed free trisomy 21, mosaicism was present in 6(5.26%) cases and translocations were seen in 3(2.63%) cases. A case of double aneulpoidy was also seen. Average maternal age at the time of birth of DS child was 27.5 years. We found that 25.44% mothers experienced one miscarriage before the birth of a DS child and 7.89% had death/still birth. Average age of DS child referred to the Department was 3.5 years (44 months 6 days) and most of them were either first or second born. In the present study, 49.12% of DS children were diagnosed within first year of life. About 14.9% parents of DS were daily wagers. Birth of DS children was higher in the month of February and least in the month of October. Early diagnosis, karyotyping and awareness about screening tests can prove helpful in decreasing genetic burden.

Betaine–homocysteine methyltransferase 742G>A polymorphism and risk of down syndrome offspring in a Brazilian population

Down syndrome (DS) is the most common form of mental retardation of genetic etiology. Several polymorphisms in genes involved with the folic acid cycle have been associated to the risk of bearing a DS child; however, the results are controversial. Betaine-homocysteine methyltransferase (BHMT) is a key enzyme of folate pathway, and catalyzes the remethylation of homocysteine into methionine. Recent studies suggest that the polymorphism BHMT 742G>A may be associated with a decreased risk of having a DS child. We herein investigate the association of this polymorphism with the occurrence of DS in a Brazilian population. We have genotyped 94 mothers of DS infants (DSM) and 134 control mothers (CM) for this polymorphism through PCR-RFLP, and found significant differences for both BHMT 742G>A genotype (P=0.04) and allele (P=0.03) frequencies between DSM and CM. The observed genotypic frequencies were GG=0.45; GA=0.45 and AA=0.10 in CM, and GG=0.54; GA=0.38 and AA=0.02 in DSM. Allelic frequencies were G=0.68 and A=0.32 in CM and G=0.78 and A=0.22 in DSM. The presence of the mutant BHMT 742 A allele decreases 40% the risk of bearing a DS child (OR=0.61; 95% CI: 0.40-0.93; P=0.03), and the risk is diminished up to >80% in association with the homozygous genotype (OR=0.17; 95% CI: 0.04-0.80; P=0.01). Our results indicate that women harboring the single nucleotide polymorphism BHMT 742G>A have a decreased risk of a DS pregnancy, and further studies are necessary to confirm this protective effect.

Health Related Physical Fitness for Down Syndrome in Children and Adults

Physical fitness is related to health at all ages. Information about physical fitness in the Down syndrome (DS) population, however, is scarce, especially when we consider children and adolescents. A review of the current data available on this topic would be both timely and important as it would serve as a starting point to stimulate new research perspectives. The data we reviewed from the literature showed a general trend toward lower values of physical fitness parameters and worse body composition variables in children and adolescents with DS compared with the population without intellectual disability (ID) or even with the population with ID without DS. Notably, children and adolescents with DS have been described as less active or overprotected; however, these factors may not be the cause of their poor physical fitness.

A very rare cancer in Down syndrome: medulloblastoma. Epidemiological data from 13 countries

Persons with Down syndrome (DS) uniquely have an increased frequency of leukemias but a decreased total frequency of solid tumors. The distribution and frequency of specific types of brain tumors have never been studied in DS. We evaluated the frequency of primary neural cell embryonal tumors and gliomas in a large international data set. The observed number of children with DS having a medulloblastoma, central nervous system primitive neuroectodermal tumor (CNS-PNET) or glial tumor was compared to the expected number. Data were collected from cancer registries or brain tumor registries in 13 countries of Europe, America, Asia and Oceania. The number of DS children with each category of tumor was treated as a Poisson variable with mean equal to 0.000884 times the total number of registrations in that category. Among 8,043 neural cell embryonal tumors (6,882 medulloblastomas and 1,161 CNS-PNETs), only one patient with medulloblastoma had DS, while 7.11 children in total and 6.08 with medulloblastoma were expected to have DS. (p 0.016 and 0.0066 respectively). Among 13,797 children with glioma, 10 had DS, whereas 12.2 were expected. Children with DS appear to be specifically protected against primary neural cell embryonal tumors of the CNS, whereas gliomas occur at the same frequency as in the general population. A similar protection against neuroblastoma, the principal extracranial neural cell embryonal tumor, has been observed in children with DS. Additional genetic material on the supernumerary chromosome 21 may protect against embryonal neural cell tumor development.

Relationship between flat foot condition and gait pattern alterations in children with Down syndrome

In patients with Down syndrome (DS) one of the most common abnormalities is flat foot which can interfere significantly with normal daily activities, such as gait. The aim of this study was to quantitatively assess the relationship between the flat foot and the gait alterations in DS children. Twenty-nine patients with DS and 15 non-affected subjects were assessed using 3D Gait Analysis, using an optoelectronic system, force platforms and video recording. The degree of flat foot was assessed using the arch index and kinematic and kinetic parameters were identified and calculated from 3D Gait Analysis for each study participant. Data showed that ankle plantarflexion moment and ankle power during terminal stance were significant to differentiate the patients with and without flat feet: their peak values were significantly lower for the patients with flat foot. In addition, the research for correlation demonstrated that the higher the arch index value, the lower the peak of ankle moment and of the generated ankle power during terminal stance and the minimum of absorbed ankle power. Children with flat foot displayed a less functional gait pattern in terms of ankle kinetics than children without flat foot, suggesting that the presence of flat foot may lead to a weaker efficient walking. Then, the increasing flat foot tended to result in lower push-off ability, leading to a less functional walking.

Increased Risk of RSV Infection in Children with Down's Syndrome: Clinical Implementation of Prophylaxis in the European Union

Prospective cohort studies show that Down's syndrome (DS) is an independent risk factor for hospitalization for RSV bronchiolitis. It is unknown whether this observation has been translated into specific management for DS children. The primary goal was to assess the knowledge of healthcare providers in the European Union about RSV infection in DS children and to determine whether it influenced the implementation of prophylaxis. DS caregivers were surveyed using a standardized questionnaire, and country-specific guidelines were obtained. Fifty-three caregivers participated. Thirty-nine (86.7%) had knowledge of the increased risk of severe RSV infection in DS children, and 30 (71.4%) graded that it was important to have a statement on the use of RSV prophylaxis in existing guidelines. Twenty-eight participants had a local DS guideline; hard copies of twelve unique guidelines were obtained. Only one (8.3%) contained a statement on RSV prophylaxis for DS, and five considered such a statement for the next version. Conclusion. Most pediatricians had knowledge that DS children have an increased risk of severe RSV infection. Despite the lack of a specific RSV prophylaxis trial in DS, they felt that a statement on RSV prophylaxis in DS guidelines was important, but this was rarely present in current guidelines.

Dietary Practice and Physical Activity in Children with Down Syndrome and Their Siblings in Saudi Arabia

Background: Feeding difficulties and inappropriate nutrition are common problems among children with Down Syndrome (DS). Objective: The aim of this study is to investigate the dietary practice and physical activity among children with DS. Methodology: The study groups were pre-pubertal DS boys and girls, aged 5 to 12 years clinically and cytogenetically proven to be suffering from DS. Healthy siblings, closest in age to the DS children were used as a control group. Breast feeding, eating difficulties, fast food intake, and physical activity were measured for both groups. Results: During infancy period, 36.4% of the DS children were bottle fed, compared to only 5.5% of the normal siblings. Nearly half of the breast-fed DS children were fed for duration of less than 6 months. The percentage of the DS children experiencing dietary difficulties is significantly higher compared to the siblings. Concerning physical activity, 73.1% of DS children did not exercise as compared to 44.2% of the control siblings. Conclusion: Controlling feeding practices and encouraging Down syndrome children to participate in physical activity either through support from parents or through designing special programs and facilities and are two avenues that can be used for obesity prevention.

Prevalence of methylenetetrahydrofolate reductase 677 C-T polymorphism among mothers of Down syndrome children

INTRODUCTION:The relationship between chromosomal non-disjunction leading to aneuploidy and folate metabolism has drawn attention in the recent years. In this study, we examined the polymorphism in the gene encoding the folate metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR), namely, 677 C-T in women having Down syndrome (DS) children.MATERIALS AND METHODS:The prevalence of these variant genotypes (MTHFR 677 C-T polymorphism) in women having DS children (case mothers) (n = 110) was compared with controls (n = 111) from Punjab. Genotyping was done using the polymerase chain reaction method followed by restriction fragment length polymorphism.RESULTS:In the present study, 1.8% of case mothers had TT genotype while none of the control mothers showed this genotype. T allele frequency among cases was 0.13 and 0.11 in controls. The Chi-square value showed a non-significant difference between cases and controls.CONCLUSION:No association has been observed between 677 C-T polymorphism and risk of non-disjunction in case mothers. Detection of polymorphisms in more genes of folate pathway is required to find out the exact cause of non-disjunction.

Posture control after 5 months body balance training in Down syndrom children and youth

AbstractAim of the study: The aim of this study was to verify whether the 5-month training exercises using specific balance exercises of the authorial program improves body balance control in children with Down syndrome (DS).Materials and methods: The purpose of this study was the verification if the 5-months posture control exercises training by original program relays to posture control in Down syndrome (DS) children and youth. The subjects were 8 DS persons: 4 males and 4 females, aged 13-24. Two 20-seconds consecutive trails of natural bipedal standing position on 2 force platforms AccuSway (AMTI), one under each foot, were performed during research. On the basis of COP (centre of pressure) time series the following indices were computed: range, variability, velocity and area of COP shifts. There were 2 sessions of the research: one just before and the second just after 5-month lasting specific posture control training based on the original exercise program.Results: The results revealed decreasing of the COP velocity of right lower limb and the COP range in anterior-posterior direction of both lower limbs after the training, comparing to the values from the first research session.Conclusions: It is concluded that the specific posture control training by the presenting of the original exercises program influenced the posture control improving it and the program can be used in therapy of DS children and youth.

Echocardiography in children with Down syndrome.

Congenital heart disease is a common problem in children with Down syndrome (DS). Echocardiography plays an important role in the detection of both structural and functional abnormalities in this group of patients. Fetal echocardiography can help in the early recognition of DS by detecting soft markers of DS, but its main role is to define the exact nature of the suspected cardiac problem in the fetus. Postnatal echocardiography is mandatory in the first month of life for all neonates with DS. It is also indicated before any cardiac surgery and for serial follow-up after cardiac surgery. In this article, we discuss the types and mechanism of cardiac abnormalities in DS children and the role of both fetal and postnatal echocardiography in the detection of these abnormalities.

Maternal SNPs in the p53 Pathway: Risk Factors for Trisomy 21?

The p53 family and its regulatory pathway play an important role as regulators of developmental processes, limiting the propagation of aneuploid cells. Its dysfunction or imbalance can lead to pathological abnormalities in humans. The aim of this study was to evaluate the effect of maternal polymorphismsTP53c.215G>C (P72R),TP734 c.-30G>A and 14 c.-20C>T,MDM2c.14+309T>G (SNP309),MDM4c.753+572C>T andUSP7c.2719-234G>A as risk factors for Down Syndrome (DS) birth. A case-control study was conducted with 263 mothers of DS children and 196 control mothers. The distribution of these genotypic variants was similar between case and control mothers. However, the combined allelesTP53C andMDM2G, andTP53C andUSP7A increased the risk of having offspring with DS (OR = 1.84 and 1.77; 95% CI;P< 0.007 and 0.018, respectively). These results suggest that, although the individual polymorphisms were not associated with DS birth, the effect of the combined genotypes amongTP53,MDM2andUSP7genes indicates a possible role ofTP53and its regulatory pathway as a risk factor for aneuploidy.

Comparative study: Parameters of gait in Down syndrome versus matched obese and healthy children

Being severely overweight is a distinctive clinical feature of Down syndrome (DS). Down syndrome is a complex multisystem disorder, representing the most common form of genetic obesity. The purpose of this study was to compare the spatiotemporal parameters of gait in genetically obese DS children and non-genetically obese children and compare their results with those obtained in a group of normal-weight control subjects. Fifteen patients with DS, 15 obese matched children and 15 healthy subjects from both sexes represented the sample of this study. Their age ranged from 12 to 14years. Spatiotemporal gait parameters (total distance, step length, average step cycle, and walking speed) were assessed by using a Biodex Gait Trainer 2™. Obese DS patients walked slower for a short distance, had a shorter step length and a lower cadence compared with both matched non-genetically obese and healthy subjects. Also, non-genetically obese matched children showed spatio-temporal gait parameters significantly different from healthy subjects. Subjects with DS had a gait pattern significantly different from obese children despite that both groups had a similar body mass index (BMI). Gait abnormalities in children with DS may be related to abnormalities in the development of motor skills in childhood, due to precocious obesity. A tailored rehabilitation program in the early childhood of DS patients could prevent gait pattern changes.