Number skills for individuals with Down syndrome - An overview

Down syndrome (DS) or Trisomy 21, occurring in 1/700 and 1/1000 livebirths, is the most common genetic disorder, characterized by a third copy of the human chromosome 21 (Hsa21). DS is associated with various defects, including congenital heart diseases, craniofacial abnormalities, immune system dysfunction, mental retardation (MR), learning and memory deficiency. The phenotypic features in DS are a direct consequence of overexpression of genes located within the triplicated region on Hsa21. In addition to developmental brain abnormalities and disabilities, people with DS by the age of 30-40 have a greatly increased risk of early-onset of Alzheimer’s disease (AD) and an apparent tendency toward premature aging. Many of the immunological anomalies in DS can be enclosed in the spectrum of multiple signs of early senescence. People with DS have an increased vulnerability to oxidative damage and many factors, including amyloid beta protein (Abeta), genotype ApoE4, oxidative stress, mutations in mitochondrial DNA (mtDNA), impairment of antioxidant enzymes, accelerated neuronal cell apoptosis, are related to neuronal degeneration and early aging in DS. SUBJECTS and METHODS: Since 2007 a population of 50 adolescents and adults with DS, 26 males and 24 females (sex-ratio: M/F = 1.08), has been evaluated for the presence of neurological features, biomarkers and genetic factors correlated with neuronal degeneration and premature aging. The control group was determined by the mother and the siblings of the patients. A neuropsychiatric evaluation was obtained from all patients. The levels of thyroid antibodies (antiTg and antiTPO) and of some biochemical markers of oxidative stress, including homocysteine (tHcy), uric acid, cobalamin, folate were measured. All patients, the mother and the siblings were genotyped for ApoE gene. RESULTS: 40% of patients, with a mild prevalence of females aged between 19 and 30 years, showed increased levels of antiTg and antiTPO. The levels of tHcy were normal in 52% patients and mildly increased in 40%; hyperomocysteinemia was associated with normal levels of thyroid antibodies in 75% of patients (p<0.005). The levels of uric acid were elevated in 26%. Our study showed a prevalence of severe MR in patients aged between 1-18 years and over 30 years. Only 3 patients, 2 females and one male, over 30 years of age, showed dementia. According to the literature, the rate of Down left-handers was high (25%) compared to the rest of population and the laterality was associated with increased levels of thyroid antibodies (70%). 21.5% of patients were ApoE4 positive (ApoE4+) with a mean/severe MR. CONCLUSIONS: Until now no biochemical evidence of oxidative damage and no deficiency or alteration of antioxidant function in our patients with DS were found. mtDNA sequencing could show some mutations age-related and associated with oxidative damage and neurocognitive decline in the early aging of DS. The final aim is found predictive markers of early-onset dementia and a target strategy for the prevention and the treatment of diseases caused by oxidative stress. REFERENCES: 1) Rachidi M, Lopes C: “Mental retardation and associated neurological dysfunctions in Down syndrome: a consequence of dysregulation in critical chromosome 21 genes and associated molecular pathways.” - Eur J Paediatr Neurol. May;12(3):168-82 (2008). 2) Lott IT, Head E: “Down syndrome and Alzheimer's disease: a link between development and aging.” - Ment Retard Dev Disabil Res Rev, 7(3):172-8 (2001). 3) Lee HC, Wei YH: “Oxidative Stress, Mitochondrial DNA Mutation, and Apoptosis in Aging.” - Exp Biol Med (Maywood), May;232(5):592-606 (2007).

More people with an intellectual disability are now living to older age and there is a paucity of information about this group of people. Mental illness is 2-3 times more prevalent in people with an intellectual disability than in the general community; however, this often goes undiagnosed and undetected. Additional issues complicate assessment if the person is also ageing. Little is known about the prevalence and nature of mental illness in this group of older people. Instruments used to assist in the diagnosis of mental illness in the general community are not suitable for use with individuals who have an intellectual disability. The Developmental Behavioural Checklist for Adults (DBC-A) (Mohr, Tonge & Einfeld, 2005) is a well established screen for psychopathology; however, it has no standardised norms and has not been specifically validated for older adults. Lack of knowledge and inadequate assessment processes can result in inappropriate service delivery and therefore reduced quality of life for older people with an intellectual disability and their carers. The general aim of the research was to contribute knowledge about older people with an intellectual disability and more specifically to investigate their mental health. In addition, the validity of the DBC-A for use with older adults was examined. An epidemiological study of adults aged 55 years and older, who lived in representative areas in South Australia, and who were registered with intellectual disability service agencies, were surveyed. Familiar informants completed a questionnaire booklet (see Appendix A). The Adaptive Behaviour Dementia Questionnaire (ABDQ) (Prasher, Farooq & Holder, 2004) and, for a subset of the participants, the Dementia Screening Questionnaire for Individuals with Intellectual Disability (DSQIID) (Deb, Hare, Bhaumik et al., 2007a) were also completed (see Appendices F and G). There was a participation rate of 91.7% and participants’ ages ranged from 55-86 years, the majority being males (56.6%), except in the oldest cohort. Those aged 55-64 years appears to differ from those who are older and younger. They have more severe intellectual impairments, more chronic health conditions, they are less likely to be engaged in activities, and have fewer relationships. Those older than 65 years are more similar to older people without an intellectual disability except that more live in nursing homes or larger congregate care settings. Standardised normative data was established for the DBC-A for older people. The DBC-A profile showed age-associated decline in psychopathology; however, the intensity of behaviours was higher in older people with more severe cognitive impairment. Significant psychopathology was found in 16% of older adults. There were no gender differences but those with a moderate level of intellectual disability had the highest rates. Being younger, having fewer hours in activity, living in large congregate care and significant life events were all risk factors. Rates of dementia of between 5-7% were found using the ABDQ, DSQIID and respondent report. A dementia screen using items from the DBC-A (DBC-A Dem) identified almost double that number. There was no association between age and dementia status in this study, which differs from other research, as does the lack of relationship between having Down syndrome and dementia status. The results of this study confirm a picture of differential mortality and the presence of a healthy survivor cohort who have fewer chronic health problems and are more likely to have a mild level of intellectual disability. Although there is an age-related decline in the prevalence of mental illness, rates are still one and a half times more than older people who do not have an intellectual disability. With minor amendments, the DBC-A is a valid screening instrument for use with older people with an intellectual disability. It can record changes in a wide range of emotional and behaviour disturbances including those that may affect older people, including dementia. When used with other DBCs for children and adolescents (Einfeld & Tonge, 1995) it provides a simple and familiar way to record psychopathology throughout the lifespan. This offers clinicians, researchers and service providers a means to monitor and maintain the mental health and well-being of older people with an intellectual disability.

Objective To assess the clinical application values of the protein markers associated with Down syndrome （DS）in maternal serum which were screened and identified. Methods Seven maternal serum samples with DS fetus （DS group） and 7 maternal serum samples with normal fetus （control group） in the second trimester were separated by two-dimensional gel electrophoresis （2-DE）.The differentinal expression profile of proteome in maternal serum from DS group was established.The differentially expressed proteins were screened by mass spectrometry （MS） and some proteins were verified by Western blotting （WB）. Results Twenty-nine proteins were discovered to be differentially expressed by more than 1.5 folds in maternal serum from DS group, among which 19 proteins were up-regulated and 10 proteins were down- regulated.Eight proteins displayed 2 or more folds changes in maternal serum from DS group were identified by MS and possibly matched with 12 proteins in Ameracan National Center of Biotchnology Information （NCBI） protein sequence database, such as dGTPase and Beta2-Glycoprotein I （β2-GPI）, etc.The results of WB showed that the mean a values of dGTPase and β2-GPI were 21 567.0±3009.4 and 22 097.0±3958.9 in the DS group, 3957.7±250.9 and 1799.7±105.5 in the control group respectively, which presented that the expression of dGTPase and β2-GPI significantly increased in DS group (t′dGTPase=-17.66，t′β2-GPI=-14.83，P＜0.0001). Conclusions 2-DE and MS are effective methods for preliminary identification of protein markers associated with DS in maternal serum.dGTPase and β2-GPI verified by WB laid a solid fundation for further screening new biologic markers for early diaglosis of DS.(Chin J Lab Med， 2012,35：328-332) Key words: Down syndrome; Blood proteins; Biological markers; Proteomics

Objective: The maternal use of folic acid supplementation particularly during the preconception period has been suggested to thwart Down syndrome, thus the awareness among the mothers of Down syndrome children regarding folic acid consumption and other factors was assessed in this study. Methods: In this population-based case study, mothers of children with Down syndrome [n=192] living in the city of Riyadh, Kingdom of Saudi Arabia, were enrolled through schools run by The Down syndrome society. Using a specially structured questionnaire that included questions on socio-demographic variables, women’s knowledge about folic acid supplementation, and timing of supplementation was evaluated. Results: Analysis of data indicated children born to mothers who were 35 and above failed to follow recommended Folic acid supplementation. Around 70% percent of the DS mothers started taking supplementation after a confirmed pregnancy. Children were more likely to be born with DS if they were the 4th or more, child born to the same mother in the family. The rate was observed to be higher if they were born to mothers with even higher parity [>4]. Conclusion: The results of this study imply that folic acid supplementation is crucial for the prevention of Down syndrome before conception, as well as for the post-conception period in all women, especially for women who are 35 years and over and women with high parity.

Down syndrome or trisomy 21 is a condition where extra genetic material causes mental and physical delays and deficits. It affects 1 in every 650 babies. Abnormalities of the cardiovascular system are common in down syndrome. Approximately half of all infants born with down syndrome have a heart defect. The most common heart defects in down syndrome are the following: atrioventricular septal defect (45%), ventricular septal defect (35%), atrial septal defects (8%) and patent ductus arteriosus (7%), tetralogy of Fallots (4%). A Two years one-month-old baby was admitted in cardiac surgery department of Dhaka Shishu Hospital, with the diagnosis of Down syndrome with VSD,ASD& PDA with moderate pulmonary arterial hypertension. Clinical examination revealed diastolic murmur over mitral area. The child was treated with face musk oxygen, diuretics and digoxin and was stabilized medically and then was selected for surgery. We used balanced anesthetic technique using oxygen, air, fentanyl, midazolam and vecuronium. Patient was operated under cardiopulmonary bypass (CPB) with moderate hypothermia. Patient tolerated the whole procedure well and was ventilated electively for 4hrs in the intensive care unit. He was discharged on the 8thpostoperative day. Journal of Bangladesh Society of Anaesthesiologists 2015; 28(1): 39-42

Isokinetic arm and leg strength of adults with Down syndrome: a comparative study.

Down syndrome is a common chromosomal abnormality associated with many different structural anomalies. Tracheomalacia results in tracheal collapse when increased airflow is demanded due to the flaccidity of the tracheal support cartilage. Sufficient research and data are currently not available on airway malformations associated with Down syndrome, including tracheomalacia. In this case report, we discuss a Down syndrome patient with pneumonia found to have narrowing of his airway which resulted in prolonged hospital stay and difficulty in management. In most children with Down syndrome, tracheomalacia, tracheobronchomalacia, and bronchomalacia are all under diagnosed, yet these anomalies are more commonly missed in adults with Down syndrome. This can result from the patient’s presentation, which tends to be non-specific, and unless a specific obstruction is considered, it is unlikely that such forms of narrowing will be discovered. Severe adult tracheomalacia is a severe condition that can be difficult to treat, especially when associated with an airway infection that may result in increased mortality rates. J Med Cases. 2015;6(10):460-462 doi: https://doi.org/10.14740/jmc2287w

Chromosome 21 is the smallest human chromosome and represents a model for physical mapping of the entire human genome. Three copies of this autosome cause Down syndrome, the most frequent genetic disorder associated with significant mental retardation. Five years ago, in the framework of the international human genome project, and as an integrated part of the chromosome 21 community, a consortium, of academic groups from Japan and Germany was formed to map and sequence this chromosome. Several whole-genome and chromosome-specific DNA libraries were constructed for mapping purposes. Using a combination of nested-deletion [1] and shotgun sequencing approaches, our center determined and analyzed over 17 million bases of high-quality data. In total, over 33.5 million basepairs of DNA, distributed over four contigs, were sequenced with very high accuracy [2]. The largest of these contigs is nearly 25.5Mb long. Only three small clone gaps remain, which together comprise approximately 100kb. Thus, we achieved a coverage of 99.7% of 21q. In addition, 211,116 bp from the short arm were also sequenced. Analysis of the chromosome revealed far fewer genes than previously estimated. Instead of 800-1000 expected genes, we found only 225 genes, of which 127 are known genes and 98 are predicted genes. In addition, 59 pseudogenes were identified. The completion of the 21q sequence provides a unique resource for understanding the molecular pathophysiology of Down syndrome, as well as all other monogenic and complex disorders that map to this chromosome, including Alzheimer’s disease, leukemia, autoimmune disease, epilepsy and manic-depressive psychosis. It also stands as a structural framework from which the complete molecular architecture of the chromosome can be determined. With the announcement of the first “working draft” of the human genome by the international human genome sequencing consortium this past June, there has been a great interest in the total number of genes in the human genome[3]. Some of the current estimates range from as low as 34,000 genes to as high as 140,000 genes. The low gene-density of chromosome 21 was quite unexpected. Most striking is a 7-Mb region near the region near the centromere that contains only one gene. This region is much larger than the whole genome of some species, such as Escherichia coli, yet evolutionary processes permitted the existence of such a gene-poor SNA segment. This finding leads us to propose that there are additional large gene-less regions in other human/mammalian chromosomes. By combining the gene numbers of chromosomes 21 and 22 [4] (770genes; 2-3% of human genome) and assuming that together they represent the average gene content of the human genome, we estimate that the total number of human genes may be close to 40,000. As part of the international human genome sequencing project, we are also sequencing parts of chromosomes 11 and 18. Our high-throughput sequence production line generates about 10 Mb per day. In order to handle such a high volume of output, we have developed a system for automated data assembly, annotation and release. All the data is released through our website and through the DNA Database of Japan immediately according to the policies established by the international consortium. In addition to chromosomes 11, 18 and 21, we are also interested in the structure of the entire human genome. In collaboration with the University of Tokyo, we have developed a database called HGREP [5] (Human Genome Reconstruction Project) that contains working draft and finished sequences which cover more than 85% of the human genomic sequences. Sequence entries are aligned along the chromosomes based on sequence similarities to STS markers, BAC-end and other entry sequences. Further, biological features, such as genes, gene functions, repeats and CpG islands, are fully annotated on these entries. To identify evolutionally conserved and biologically important information in the genome, we are taking the strategy of comparative genomic sequence analysis between human and other related genomes such as those of rodents and primates. We are currently sequencing several regions of the mouse, including some regions that are counterpart to human chromosome 21, and are preparing genomic resources for sequencing of the chimpanzee. Through comparative methods, we are also trying to understand telomeric regions, structures at the end of chromosomes that play an important role in several biological functions and have been associated with human diseases like an oncogenesis and a cellular aging. The structure and function of all genes and their regulatory regions can only be fully understood by looking at how they interact under different circumstances and in several different backgrounds. Determining which genes and elements are human-specific will lead to a deeper understanding of who we are and will advance medical sciences drastically.

A case of a 15-year-old Chinese girl with Down’s syndrome is presented in this report. Besides the common clinical manifestations for persons with Down’s syndrome, the girl has a rare oral anomaly, which is the delayed eruption of all the permanent teeth with primary dentition retained. J Med Cases. 2015;6(6):277-278 doi: https://doi.org/10.14740/jmc2166w

The area of study grew out of the author's experiences during her practical in Warwickshire and Coventry schools, and from her concerns as a pre-service teacher about class control, pupils' responses to her reprimands and the pupils' subsequent behaviour. The purpose of the study was to investigate the nature and extent of pupil misbehaviour incidents in secondary school mixed-sex physical education lessons, and the responses of experienced male and female physical education teachers to those incidents. Ten schools were randomly selected from forty-five co-educational secondary schools within a twenty-five mile radius of an East Midlands University. Coders, working in pairs and trained in the data-collecting procedures, observed 119 mixed-sex physical education lessons in fourteen activities, and they recorded 593 pupil misbehaviour incidents. The number of intact classes observed. in each school ranged from ten to fourteen with the length of the lesson ranging from twenty-five to seventy minutes and the class size ranging from sixteen to thirty-one pupils. The number of teachers involved in each school varied from two to four and, of the observed lessons, sixty-two were taught by male teachers and fifty-seven by female teachers. The majority of pupil misbehaviour incidents occurred during teachers' instructions and generally involved one pupil or a group of pupils, although a ripple effect was sometime evident. Although they usually involved one pupil or a group of pupils, a greater number of pupils were affected by the incidents. The incidents were mainly teacher-owned and the teachers usually dealt with them in fifteen seconds or less. There was no significant difference in the frequency of pupil misbehaviour incidents between morning and afternoon classes but males committed significantly more misbehaviour incidents. The teachers' responses were mainly verbal with the vast majority being made in public and in a controlled and fun manner. The teachers' focus was on the pupils' behaviour, and, in taking a final action against misbehaving pupils, teachers tended to allow them to remain in the class. Male teachers had more disruption between pupils but less attentional incidents than female teachers, and in their responses to pupil misbehaviour incidents they were less verbal, more private and more controlled and firm.

Congenital leukemia is very rare, diagnosed in first month of life and often associated with Down’s syndrome. Congenital Acute myeloid leukemia (AML) is more common over acute lymphoblastic leukemia (ALL). The hematological parameters such as anemia, low hematocrit, reduced RBC count, reduced platelets are distinct characteristics against normal parameters in very closely associated Transient myeloproliferative disorder (TMD). The immunophenptypic markers such as expression pattern of CD13, CD11b and HLADR in combination can be used for distinguishing two diseases. The morphological discrimination between congenital AML and TMD is little difficult and hence combined results of hematological, cytogenetic and immunophenotyping should be considered while concluding the cases. We here report two cases observed in year 2014 in our hospital, at pune. Both the cases were diagnosed in first week of their life, day 2 (case 1) and day 8 (case2) with distinct features of increased white blood cell count with myeloid blast, reduced Hb, low hematocrit, reduced RBC count and low platelets count with trisomy 21. Both the cases were CD13- and CD11b +, hence we conclude these cases as Congenital Acute myeloid leukemia associated with Down’s syndrome. Both the cases survived for less than 15 days after the birth.

Mathematics has been viewed as the most difficult subject in the secondary school particularly by children in developing countries (Skemp 2008). And yet in spite of it being perceived as a difficult subject, mathematics is a fundamental part of human thought and logic and integral at attempts to understanding the world and ourselves. Evidence shows that students in many countries fail mathematics (Lynons 2010). Literature has a plethora of reasons for high failure rate of mathematics. For example, Polya (2011) states that shortage of well-trained teachers, inadequacy of teaching facilities, poor quality textbooks, large classes, poorly motivated teachers, poorly coordinated supervisory activities, incessant transfers of teachers and heads, automatic promotion of pupils, the negative role of public examinations, and inequality of educational opportunities, all hamper the smooth acquisition of mathematics knowledge. As a result of this situation, there has been a sudden deluge of supplementary tuition or extra-tuition. The practice of offering extra tuition has both social and economic implications on those involved. Parents pay the regular school fees and are then asked or volunteer to part with more money in the form of tuition for extra-lessons. This study sought to investigate teachers’ perceptions on the role played by supplementary-tuition or extra-lessons on the performance of pupils at ordinary level in secondary schools in Hwange District in Zimbabwe. The population comprised of 450 secondary school teachers in the district. Random sampling was used to arrive at a sample of 100 respondents who comprised of 58 females and 42 males. The study adopted the descriptive survey design and the questionnaire was the major instrument for collecting data. The main findings indicated that teachers felt that supplementary tuition in mathematics improved the results of those pupils who received it. The study also revealed that teachers felt that time allocated for mathematics was inadequate. The recommendations are that time allocated to mathematics should be increased right from the primary school to the secondary school level. Another recommendation was that properly qualified teachers to teach mathematics should be deployed in all the schools to avoid supplementary-tuition. Keywords: Supplementary tuition, Ordinary level, Student, Mathematics, Teachers, Tuition, Extra-tuition

Children with Down's syndrome(DS) are at the highest risk for intellectual disability.This article presentes information on the neuropathology attributed to cognition impairment in DS, also presented are the major medical concern and management strategies for an individual with DS from birth to young adulthood. Key words: Down's syndrome; Cognition; Neuropathology

The focus of this quasi-experimental pilot study is how to support the emergence of the full potential development of nonverbal social skills in children with Down syndrome (DS). It is an exploratory case study using an embedded-multiple case design. This study views working with the social skills of a 6-year-old girl with DS through the lens of the Kestenberg Movement Profile (KMP). Through this lens, the social intelligence, relational shaping, developmental movement, and nonverbal communication of a child with DS were explored. In order to more accurately identify the child's strengths and challenges a triangulation approach is used. Data were collected for the child with DS and her typically developing, fraternal, twin sister using the Vineland Adaptive Behavior Scales-II as a quantitative assessment tool, the KMP as a qualitative assessment tool, and from a naturalistic observation in their home environment in order to assess and compare their nonverbal social skills.

Introduction: Functional echocardiography is a rapidly expanding field in both research and clinical settings. Newer techniques facilitate comprehensive and objective assessments of myocardial performance not previously possible. Although work has been done to assess feasibility and obtain reference values for several new modalities in normal term and preterm infants, data is still lacking in several important disease states. Objectives: We aim to study the impact of several important conditions on neonatal myocardial function over the transitional period. We hypothesise that myocardial function is impaired in certain conditions and that novel echocardiography techniques could improve our ability to characterise disease severity and predict important outcomes. Methods: We recruited several cohorts of infants including: control preterm and term infants; preterm infants with haemodynamically significant ductus arteriosus and chronic lung disease; infants with hypoxic ischemic encephalopathy; monochorionic diamniotic twins with twin to twin transfusion; and infants with Down syndrome with structurally normal hearts. We performed three echocardiograms on Day 1 (6-12 hours), Day 2 (36-48 hours) and Day 5 – 7. We compared our results in disease patient cohorts with a cohort of healthy preterm and term infants. Results: We have characterised myocardial performance in: preterm infants with and without disease; healthy term infants; infants with hypoxic ischemic encephalopathy; monochorionic diamniotic twins with and without twin to twin transfusion syndrome; and infants with Down syndrome with structurally normal hearts. We have demonstrated changes in haemodynamic status and cardiac function in these conditions and provided a rationale for these changes, in addition to exploring markers of outcome predication. Conclusion: Several important neonatal conditions affect myocardial performance during the transitional period. An improved understanding of cardiac function can aid in our ability to predict outcome and monitor disease. In the future, functional echocardiography may act to guide intervention and improve our management of these patients.