Article

Incidence of Down syndrome in Dubai, UAE

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

To describe incidence of Down syndrome in Dubai, United Arab Emirates (UAE). A total of 63,398 newborn babies in Dubai (24,250 UAE nationals and 39,148 non-UAE) during a 5-year period of 1999-2003 were routinely examined by experienced nurses, neonatologists, pediatricians and/or general practitioners for symptoms of Down syndrome. Those suspected with Down syndrome were referred to the cytogenetic laboratory for karyotyping. A total of 141 cases were confirmed cytogenetically as Down syndrome. Of these, 139 were trisomy 21 and of the remaining 2, 1 was a translocation and the other a mosaic. Theoverall incidence of Down syndrome in Dubai was 1/449 live births (2.2 per 1,000); 1/319 live births (3.13 per 1,000) among UAE nationals and 1/602 live births (1.66 per 1,000) among non-UAE nationals. The mean maternal age of UAE national mothers was 33.48 +/- 8.08, with 41.66% of the mothers being in the advanced maternal age group (>35 years). The higher incidence of Down syndrome among UAE nationals is comparable to incidences reported for other Arab populations in the Middle Eastern region. Advanced maternal age, with mothers bearing children until their 50s and higher parity, appear to be the major contributing factors for the increased incidence. The study indicates the need to provide efficient genetic counseling and to introduce an effective antenatal screening program and prenatal diagnostic services to reduce the psychological and genetic burden on the families and community.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Caused by an additional partial or complete third copy of chromosome 21, patients with DS often present with varying severities of learning disability, growth retardation, and other medical abnormalities [6]. With regards to the UAE, a study conducted by Murthy and authors during a 5-year period between 1999 and 2003, including a total of 63,398 newborn babies in Dubai, determined the overall incidence of DS in this population to be 2.2 per 1,000 live births [7]. The authors reported that higher incidence rates of DS, compared to the global rates, may be due to advanced maternal age-with mothers bearing children until their 50s, multiparity, and the practice of consanguineous marriages [5,7]. ...
... With regards to the UAE, a study conducted by Murthy and authors during a 5-year period between 1999 and 2003, including a total of 63,398 newborn babies in Dubai, determined the overall incidence of DS in this population to be 2.2 per 1,000 live births [7]. The authors reported that higher incidence rates of DS, compared to the global rates, may be due to advanced maternal age-with mothers bearing children until their 50s, multiparity, and the practice of consanguineous marriages [5,7]. They further indicated that accessible genetic counselling with the wide-scale implementation of prenantal diagnostic services, and antenatal screening programs may reduce the psychological impact of DS on families in this community [7]. ...
... The authors reported that higher incidence rates of DS, compared to the global rates, may be due to advanced maternal age-with mothers bearing children until their 50s, multiparity, and the practice of consanguineous marriages [5,7]. They further indicated that accessible genetic counselling with the wide-scale implementation of prenantal diagnostic services, and antenatal screening programs may reduce the psychological impact of DS on families in this community [7]. ...
Article
Full-text available
Depression has been commonly treated with psychotherapy and/or pharmacotherapy for several decades. Ongoing research in the field has suggested promise for behavioral activation (BA), a form of psychotherapeutic intervention, as a means of increasing engagement in adaptive activities and developing skills to counter avoidance in individuals suffering from depression. In this case report, we present the treatment course of BA for an adolescent with Down syndrome (DS), presenting with depression. A multidisciplinary approach was utilized in developing a personalized management plan for the patient since the initial presentation. Sessions at the outpatient psychiatry clinic alternated between in-person visits and virtual ones, due to circumstances associated with physical distancing with the COVID-19 pandemic. Parents were included as integral parts of the management plan, and education, strategic implementation of BA, and barriers to care were discussed extensively to support the adolescent through the course of her treatment. Within 6 weeks of introducing BA, positive outcomes were noted in the patient, with the resolution of her clinical depression. In this report, we discuss BA further as a potentially effective therapeutic approach to the treatment of depressive symptoms in children and adolescents with DS and intellectual disabilities.
... It is the single most common genetic cause of mental retardation and is thus of major socioeconomic concern. [1,2] The overall incidence of DS worldwide is reported to be 1 per 600 to 1 per 800 live births. [3] In Egypt, the incidence of DS has been reported to be 1 per 1000 births. ...
... [1,15,23,28] On the other hand, a study in UAE reported that a child with DS was mostly the last or second last child. [2] When children are stratified by karyotypes, we found that about two thirds of translocation and mosaic children were of first or second parity compared to about half of the nondisjunction children. There are controversial reports on the parity and risk of DS, but several studies suggest an increased risk with increasing parity. ...
... [41] Another study suggested a trend toward an increasing risk of DS with the increased parity in both younger and older mothers. [45,46] [13] 673 95.4 2.7 0.7 1.2 El-Sobky and El-Sayed (Egypt) [1] 1030 93.98 3.5 1.84 0.68 Murthy et al. (UAE) [2] 141 97.9 0.7 0.7 0.7 Abdul Wahab et al. (Qatar) [20] 146 98.0 2.0 Al-Awadi et al. (Kuwait) [21] 1024 96.2 2.3 0.9 0.6 Jaouda et al. (Morocco) [22] 582 96.2 3.2 0.6 0 Shariaty et al. (Iran) [23] 579 89.5 5.3 5.2 0 Alp et al. (Turkey) [24] 456 94. [15] 1001 87.9 4.4 7.7 0 Satish (India) [29] 114 93.0 7.0 Mandava et al. (India) [30] 1572 89.1 7.1 1.8 0 Malini and Ramachandra (India) [31] 150 98.0 0.7 1.3 0 Jayalakshama et al. (India) [32] 870 86.9 8. [33] 60 90.0 3.3 6.7 0 Azman et al. (Malaysia) [34] 149 94.6 0.7 4.7 0 Biselli et al. (Brazil) [35] 387 92. [1,14,22,24,34,37] However, other studies reported a much younger maternal age. ...
Article
Full-text available
BACKGROUND: Down syndrome (DS) is the most common chromosomal disorder. It has three chromosomal patterns. AIM: To determine the cytogenetic and comorbidity profiles of DS in the Genetic Unit of Mansoura University Children’s Hospital, Mansoura, Egypt. MATERIALS AND METHODS: A retrospective analysis was performed on the case records of 712 cytogenetically diagnosed cases of DS at the Genetic Unit of Mansoura University Children’s Hospital, Egypt, during a 10-year period. RESULTS: About 19% of the cases had one or more cardiac anomalies and about 8% were hypothyroid. Nondisjunction was the most common type of abnormality, followed by translocation and lastly mosaic: 96.1, 3.1, and 0.8%, respectively. Hypothyroidism was significantly more common in translocation and mosaic karyotypes than in the nondisjunction karyotypes. First and second birth orders were significantly higher in the translocation and mosaic groups than in the nondisjunction group. Mothers are significantly older at the index pregnancy in the nondisjunction group than in the other two groups. We compared our findings with those of previous studies. CONCLUSION: Knowing karyotype of DS will help in genetic counseling of the parents. Wide-scale national community-based survey with DS registry could help in estimating the size of the problem. Key words: Down syndrome, karyotypes, mosaic, nondisjunction, translocation
... [6] In the Middle East and North Africa region, the reported incidence of DS in Dubai is the highest The incidence is reported to be 1 in every 319 live birth in the United Arab Emirates (UAE) citizens and 1 in every 602 live births in expatriate children. [7] The advent of better health-care practices leads to better life expectancy in DS individuals. [1] DS population are better integrated with their counterparts in schools, work, and community. ...
... Studies conducted in the UAE reported higher prevalence of caries and periodontal disease. [11,15] As Dubai has the highest DS incidence in the region, [7] oral condition of the DS children in Dubai in particular, and the UAE in general must be investigated to get baseline data and guide the authorities in the provision of proper oral health care for this group. ...
... Since there is no central DS registry data in the UAE, particularly in Dubai, an accurate estimate of the percentage of DS is difficult. The only generated data suggests that DS incidence in Dubai was 1 in every 319 live birth among UAE nationals, and 1 in 602 live births among nonnationals, [7] which is the highest in the Middle East region. This might be attributed to increased maternal age and consanguineous marriages. ...
Article
Objectives: The purpose of this study was to assess the oral health status in Down syndrome (DS) children in Dubai, United Arab Emirates. Materials and methods: A total of 106 DS children (mean age = 9.3 ± 2.8) and 125 healthy children (mean age = 11.7 ± 4.4) were recruited from both special needs centers and private/public schools in Dubai. A dental examination for decayed-missing-filled teeth (DMFT) in deciduous dentition/DMFT in permanent dentition indices, simplified oral hygiene index, calculus index (CI), were carried out. In addition, occlusal, dentofacial, soft-tissue abnormalities, and erosion were assessed. Statistical analysis was conducted using SPSS for Windows, version 20.0 (SPSS Inc., Chicago, IL, USA). Results: The mean number of DMFT in DS children was significantly higher than that in healthy children. DS children in the primary dentition group had higher restorative index and Met Need Index scores than the control group. On the other hand, CI was found to be significantly higher among children with DS compared to healthy controls (P < 0.004). DS children had a significantly higher proportion of open bite and other occlusal problems. Class III molar angle malocclusion was significantly higher in DS (66%) compared to controls (11.2%). Erosion was significantly higher among DS children compared to healthy control (34% vs. 15.3%). Conclusions: DS children in Dubai had higher caries rate compared to healthy children. DS group received more restorations and dental treatment compared to the control group. More to add, DS children had significantly more calculus, erosion, and malocclusion problems.
... Approximately 40-50% of DS infants have CHD. The most common type of CHD seen in DS patients is Atrioventricular Septal Defect (AVSD) and Ventricular septal defect (VSD).Apart from AVSD and VSD, other heart defects like atrial septal defects (ASD), tetralogy of fallot (TOF) and patent ductus arteriosus (PDA) are also frequently seen in these patients (Sheffield et al., 1997;Robinson et al., 2003;Canfield et al., 2006;Murthy et al., 2007). ...
... Partial AVSD, also called as ostium primum atrial septal defect, is seen mostly in non-syndromic AVSD often occurring with a mitral cleft. Till date, 5 AVSD loci have been identified of which CRELD1 gene on 3p25.3 is AVSD 2 locus (Sheffield et al., 1997;Robinson et al., 2003;Canfield et al., 2006;Murthy et al., 2007). CRELD1 (Cysteine -Rich Protein with EGF-Like Domains) belongs to epidermal growth factor-like family and encodes a cell surface protein that likely functions as cell adhesion molecule (Fadista et al., 2016). ...
... CRELD1 gene has 11 exons which spans around 12 kb and encodes a novel cell adhesion molecule that is expressed during cardiac cushion development. Subsequently, it was shown that missense mutations in CRELD1 are a dominant susceptibility factor for AVSD both in euploid (Murthy et al., 2007) and DS individuals (Canfield et al., 2006). In present study, we studied the presence and relevance of CRELD1 mutations in DS patients with AVSD. ...
... This result agrees with previous studies in the UAE and Dhaka. 23,48 Several studies suggest an increased risk of DS with increasing parity 6 that is the same as our result, but at the same time, other studies reported that there is no increased risk with increasing parity. 49 Age of marriage in this last years became higher than the age in the earliest years, so the age at the first birth became higher. ...
... It was reported in many previous studies in different countries: India, 50 Turkey, 51 Malaysia, 31 England and Wales, 38 Jordan, 28 Saudi Arabia, 20 Tunisia, 16 and Dubai. 23 Many other studies had shown increased number of DS babies born to the young mothers, like the study of Kava and his collaborators in India, the maternal age at birth of affected children was 26.8 years. 50 Other study in the same country reported a mean of 24.95 years. ...
... 29 While for European countries, the value of free trisomy 21 was around 94%, except in Bosnia and Herzegovina, where the frequency was lower than found in other European countries (82.1%). 41 Previous studies have reported that the frequency of translocation DS varied from 0.67% to 8.8%, where the lowest frequency was noted in Iran, the UAE, and Malaysia, 23,31,29 and the highest frequency was reported in India (8.8%). 4 The frequencies around 4% were noted in Tunisia (4.1%), 16 Saudi Arabia (4.1%), 20 India (4.1%), 32 Australia (4.1%), 46 and Brazil (4%). ...
Article
Full-text available
Background: Down syndrome (DS) is the most common type of chromosomal trisomy found in newborn. It is associated with mental retardation and characteristic facial features. A clinical diagnosis of DS may be unconfirmed in one‑third of cases. Objective: This study was conducted to confirm the clinical diagnosis of suspected cases with DS by a cytogenetic analysis and to evaluate several risk factors associated with trisomy 21 in a group of patients from West region of Algeria, Tlemcen. Materials and Methods: Karyotype analysis was carried out for 22 patients with the clinical diagnosis of DS. GTG‑band and RTG‑band have been made according to the standard protocols. Results: Among the 22 cases with DS, free trisomy 21 was presented in 20 cases (91%). One case (4.5%) had translocation DS. One other case had mosaic DS. There was an excess of male than female; sex ratio was 1.75:1. The mean maternal age at birth of the affected children was 36.27 ± 7.59 years. It was significantly higher than this of mothers of nontrisomic children (27.83 ± 6.34 years; P = 0.0002). Higher parity was an important risk factor associated with trisomy 21, 81% of affected children were of last or second last birth order. Paternal age and consanguinity had no effect. Conclusion: The identification of specific types of chromosomal abnormalities in DS children is very significant. It greatly helped in the management of these children and to make aware the affected families about the recurrence risk and the options available. Key words: Cytogenetic analysis, down syndrome, karyotype, maternal age, Algeria
... The birth order of children with Down syndrome ranged from 1 to 10. Overall, 81% of them were of the last or second last birth orders. This result agrees with previous studies in UAE and Dhaka [19,20]. Several studies suggest an increased risk of Down syndrome with increasing parity that is the same as our result, but at the same time other studies reported that is no increased risk with increasing parity [6,21]. ...
... Advanced maternal age remains the principle risk factor for trisomy 21. It was reported in many previous studies in different countries: India, Turkey, Malaysia, England and Wales, Jordan, Saudi Arabia, Tunisia and Dubai [17,19,[24][25][26][27][28][29]. ...
... Previous studies have reported that the frequency of translocation Down syndrome varied from 0.67% to 8.8%, where the lowest frequency was noted in Iran, UAE and Malaysia and the highest frequency was reported in India (8.8%) [4,19,26,40]. The frequencies around 4% were noted in Tunisia (4.1%), Saudi Arabia (4.1%), India (4.1%), Australia (4.1%) and Brazil (4%) [28,29,36,42,43]. ...
Article
Background: Down syndrome (DS) is the most common type of chromosomal trisomy found in new-born. It’s associated with mental retardation and characteristic facial features. A clinical diagnosis of Down syndrome may be unconfirmed in one third of cases. Objective: This study was conducted to confirm the clinical diagnosis of suspected cases with Down syndrome by a cytogenetic analysis and to evaluate several risk factors associated with trisomy 21 in a group of patients from West region of Algeria, Tlemcen. Materials and method: Karyotype analysis was carried out for 22 patients with the clinical diagnosis of Down syndrome. GTG- band and RTG-band have been made according to the standard protocols. Results: Among the 22 cases with Down syndrome, Free trisomy 21 was presented in 20 cases (91%). One case (4.5%) had translocation Down syndrome. One other case had mosaic Down syndrome. There was an excess of male than female; sex ratio was 1.75:1. The mean maternal age at birth of the affected children was 36.27 ± 7.59 years. It was significantly higher than this of mothers of non-trisomic children (27.83 ± 6.34 years; p=0.0002). Higher parity was an important risk factor associated with trisomy 21, 81% of affected children were of last or second last birth order. Paternal age and consanguinity had no effect. Conclusion: The identification of specific types of chromosomal abnormalities in Down syndrome children is very significant. It greatly helped in the management of these children and to make aware the affected families about the recurrence risk and the options available.
... There are about 7,000 known genetic disorders, 30 to 40% of cases cause a physical change showing abnormalities in the face and skull [3]. A study conducted by the Center for Arab Genomic Studies (CAGS): a division of Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences reported that Arabs suffer from high rates of genetic disorders [4] [5]. To address this problem, CAGS established the Catalogue for transmission Genetics in Arabs (CTGA) in 2003. ...
... According to CTGA, the incidence of DS in many Arab countries is higher than the international figures. The incidence rate among the Emiratis in Dubai is 1 in 319 live births [5]. It is slightly higher but comparable to figures from neighboring countries such as Oman (1:500) and Qatar (1:546) [6]. ...
... It is slightly higher but comparable to figures from neighboring countries such as Oman (1:500) and Qatar (1:546) [6]. Similarly, Saudi Arabia and Kuwait are also on the higher end of international incidence rates with 1:554 and 1:581 respectively [5]. One common factor in all of these countries, according to the report is the prevalence of intermarriages, especially between first cousins. ...
Article
Full-text available
The analysis of facial appearance is significant to an early diagnosis of medical genetic diseases. The fast development of image processing and machine learning techniques facilitates the detection of facial dysmorphic features. This paper is a survey of the recent studies developed for the screening of genetic abnormalities across the facial features obtained from two dimensional and three dimensional images.
... Several factors had been claimed to be associated with increased incidence of DS including: advanced maternal age, birth order of the affected children, consanguinity, and number of maternal miscarriage [14][15][16]. Down syndrome frequently encountered in our area with 1/960 being affected and this figure somewhat similar to that reported from Malaysia, Egypt and Germany [17][18][19], higher than United states, Singapore, England and Wales [20][21][22], but lower than India, most Arab countries, Iran and South Africa [23][24][25]5] and this mostly related to cultural factors as multiparity and probably exposure to environmental pollution including radiation. Ages of the enrolled patients ranged from 1 day to 35 years with a mean of 8.3±7.6 years (Median 6.1 years) and this figure is slightly higher than many international studies as about 46 enrolled patients were already diagnosed clinically and they were registered at Awat institute for mental retardation and because of the absence of routine cytogenetic techniques for such disorders. ...
... When individuals were stratified by karyotypes, mosaic DS were significantly associated with higher parity and these results are relatively compatible with data of few studies in Egypt, Iran and India [38,16,39]. On the other hand, Murthy et al [25] reported that an individual with DS were mostly the last one or second last one. Several studies suggest that there is an increasing risk with increasing parity as Doria-Rose et al [40] suggested that higher parity is associated with an increased risk of giving birth to a DS child, both for women aged more than 35 years and for women under 35 years of age, while Chan et al [41] reported that there is no increased risk noted with increased parity. ...
... Several factors had been claimed to be associated with increased incidence of DS including: advanced maternal age, birth order of the affected children, consanguinity, and number of maternal miscarriage [14][15][16]. Down syndrome frequently encountered in our area with 1/960 being affected and this figure somewhat similar to that reported from Malaysia, Egypt and Germany [17][18][19], higher than United states, Singapore, England and Wales [20][21][22], but lower than India, most Arab countries, Iran and South Africa [23][24][25]5] and this mostly related to cultural factors as multiparity and probably exposure to environmental pollution including radiation. Ages of the enrolled patients ranged from 1 day to 35 years with a mean of 8.3±7.6 years (Median 6.1 years) and this figure is slightly higher than many international studies as about 46 enrolled patients were already diagnosed clinically and they were registered at Awat institute for mental retardation and because of the absence of routine cytogenetic techniques for such disorders. ...
... When individuals were stratified by karyotypes, mosaic DS were significantly associated with higher parity and these results are relatively compatible with data of few studies in Egypt, Iran and India [38,16,39]. On the other hand, Murthy et al [25] reported that an individual with DS were mostly the last one or second last one. Several studies suggest that there is an increasing risk with increasing parity as Doria-Rose et al [40] suggested that higher parity is associated with an increased risk of giving birth to a DS child, both for women aged more than 35 years and for women under 35 years of age, while Chan et al [41] reported that there is no increased risk noted with increased parity. ...
Article
Full-text available
Down syndrome is the most common Aneuploidy in humans which is associated with developmental delay, mental retardation and several characteristic physical features. This study is aimed to determine the proportion and types of chromosomal abnormalities in patients with Down syndrome in Duhok province, Iraq, and to study the clinical profile of these patients. A retrospective analysis was performed on the case records of 86 patients confirmed clinically as Down syndrome from October 2014 to April 2015, for all enrolled cases cytogenetic analysis had done at Research Centre at College of Medicine\ University of Duhok. Among the 86 cases of Down syndrome presented over a period of 6 months, non-disjunction was present in 79 (91.9%) cases, translocation in 5 (5.8%) cases and Mosaicism in 2 (2.3%) cases. The age of the enrolled patients were ranged from 1 day to 35 years, from these patients, 37 (43%) were males and 49 (57%) were females with male to female ratio of 1:1.3. The maternal ages at the time of delivery of index babies were ranged from 21 years to 47 years. The most prominent characteristic features noted were epicanthic folds (80.2%), upslanting palpebral fissures (70.9%), protruding tongue (67.4%), sandal gap (64%), depressed nasal bridge (62.8%), and flat facial features (58.1%). Congenital heart disease seen in (26.7%) and hypothyroidism seen in (10.5%) Down syndrome mostly result from non-disjunction and efforts to establish early diagnosis and a proper screening for high association with systemic anomalies should be undertaken among the Down syndrome patients in our population
... Down's syndrome (DS) is defined as a condition that is accompanied with intellectual disability (ID) and associated with abnormalities in chromosome 21 (Roizen and Patterson 2003). The incidence of DS births in the Kingdom of Saudi Arabia is 1.8 for every 1000 live births (Niazi et al. 1995); its prevalence in other Arabian countries is approximately 1.93-3.5 per 1000 live births (Murthy et al. 2006), while the overall incidence worldwide is approximately 1.25-1.67 per 1000 live births (Niazi et al. 1995;Murthy et al. 2006). ...
... The incidence of DS births in the Kingdom of Saudi Arabia is 1.8 for every 1000 live births (Niazi et al. 1995); its prevalence in other Arabian countries is approximately 1.93-3.5 per 1000 live births (Murthy et al. 2006), while the overall incidence worldwide is approximately 1.25-1.67 per 1000 live births (Niazi et al. 1995;Murthy et al. 2006). Many individuals with DS have a sedentary lifestyle and less access to healthcare and experience poorer health than the general population (Baptista et al. 2005). ...
Article
Purpose: Children with Down’s syndrome (DS) are considered sedentary and less engaged in recommended physical activity (PA) levels. This study compared the PA levels between children with DS and healthy children in Saudi Arabia. Methods: The study included 85 children divided into two groups. The DS group comprised 37 children with DS aged 8–12 years recruited from the Down Syndrome Charitable Association and Al-Nahda Schools for DS. The healthy group comprised 41 healthy children aged 8–12 years recruited from regular schools in the same region. PA levels were measured over 7 days using a pedometer. Results: The healthy group was more active than the DS group (p < 0.05). The total PA steps per minute had significant differences between the DS (M = 7.979, SD = 2.21) and healthy groups (M = 17.512, SD = 3.08; p < 0.05). The daily step count differed significantly on weekdays and weekends between the groups (p < 0.05). Conclusions: The DS group had a high body mass index and physical inactivity compared with the second group. Obesity and physical inactivity among Saudi Arabian children with and without DS are major health concerns. Therefore, concerted efforts are needed to combat childhood obesity, promote PA, improve patient quality of life, and reduce the sedentary lifestyle among Saudi children and adolescents.
... Findings from one study in the United Arab Emirates (UAE) suggest a higher live birth incidence of Down syndrome there. The 2007 study examining >60,000 live births over 5 years found the live birth incidence to be 1:449 overall, which rose to 1:319 when considering births among Emirati nationals alone (Murthy et al., 2007). ...
... Our hospital-based cohort of mothers is notable for it's advanced maternal age. The traditional practice of multiparity generates conditions for advanced maternal age; when coupled with low uptake of antenatal diagnostic testing and no termination of pregnancy, conditions exist that support the reported high live birth incidence of DS in the UAE Emirate of Dubai found by Murthy et al. (2007). Future population-based studies would help to confirm our findings of high frequency of genitourinary anomalies in our hospital-based cohort. ...
Article
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.
... Trisomy 21 (Tri21), the cause of Down syndrome (DS), is the most common chromosome abnormality and the most common single known cause of intellectual disability in humans although approximately 80% of Tri21 pregnancies end in a miscarriage or intrauterine fetal demise, and only 20% may progress to term delivery [1,2]. The reasons causing Tri21 formation are not fully understood and maternal age is the most consistent biological factor associated with increased Tri21/DS prevalence and the major known reason leading to variable Tri21/DS prevalence ranging from 1/700-1/2,000 in different racial/ethnic populations investigated [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Standard Tri21 (47,XX,+21 or 47,XY,+21) have been consistently reported to accounts for 94-96% of all Tri21/DS cases in different racial/ethnic populations. ...
... These similarities strongly indicate that different racial/ethnic backgrounds might have played very limited influences to the genotypic variations of Tri21 if any of the influences might exist. We think those previously observed variations in different racial/ethnic backgrounds, such as, prevalence of Tri21 proportions of rare Tri21 karyotypes, M/F ratios, and clinical findings might have been influenced by differences from some non-biological factors such as policies, religions, cultures, social/economic levels, technique accessibilities, and data sources and qualities including sample sizes, ascertainment biases, analytical methods, etc. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]20]. ...
Article
Full-text available
This study describes the cytogenetic characteristics of 7,133 trisomy 21 (Tri21) identified from 247,818 consecutive postnatal cases karyotyped in a single reference laboratory in China for a period of 4 years. The average detection rate of Tri21 is 2.88% ranging from 3.39% in 2011 to 2.52% in 2014. The decreased detection rates over the years might reflect a possible impact of noninvasive prenatal testing applied rapidly in China and elective termination of affected pregnancies. 95.32% of the Tri21 karyotypes are standard Tri21, 4.53% are Robertsonian Tri21, and less than 1% are other Tri21 forms. There are more mosaic Tri21 in older children and adults, consistent with previous observations that clinical features in individuals with mosaic Tri21 are generally milder and easily missed during perinatal period. The male/female (M/F ratio) for the total 7,133 Tri21 cases and for the 6,671 cases with non-mosaic standard Tri21 are 1.50 and 1.53 respectively, significantly higher than the 0.93 for all the 247,818 cases we karyotyped, the 1.30 for the Down syndrome (DS) identified during perinatal period in China, and the 1.20 for the livebirth in Chinese population. In contrast, the mosaic standard Tri21 case has a significantly lower proportion of males when compared with the non-mosaic standard Tri21, indicating different underlying mechanisms leading to their formations. Opposite M/F ratios in different subtypes of ROB Tri21 were observed. A long list of rare or private karyotypes where Tri21 are concurrently present was identified. The large collection of Tri21 cases with a diversity of clinical findings and a wide age range allowed us to determine the frequency of the different karyotypes of Down syndrome in China, given the fact that this kind of national epidemiological data is lacking currently.
... Chromosome 21 has 40.06% repeat content material comprising brief interspersed repeatitive elements (SINEs), lengthy interspersed repeatitive elements (LINEs), and lengthy terminal repeats (LTRs) (1,2,3). The maximum suitable concept for the pathogenesis of trisomy 21 is the genedosage speculation, which announces that each one modifications are because of the presence of an additional reproduction of chromosome 21 (4). Although it's miles tough to choose candidate genes for those phenotypes, information from transgenic mice propose that only a few genes on chromosome 21 can be worried withinside the phenotypes of DS and a few gene merchandise can be extra touchy to gene dosage imbalance than others. ...
Article
Full-text available
Down syndrome (DS) is a birth defect with significant medical and social costs that is caused by trisomy of all or part of chromosome 21. It is the most common genetic disease in the world and the most common genetic cause of intellectual disabilities, affecting approximately 1 in 400-1500 newborns. Despite the fact that the syndrome had been described thousands of years before, it was named after John Langdon Down, who described it clinically in 1866. Scientists have discovered candidate genes that play a role in the development of specific DS features. These advancements, in turn, may aid in the development of targeted therapy for people with trisomy 21. Screening for Down syndrome is an essential part of routine prenatal care. Until recently, noninvasive screening for aneuploidy relied on maternal serum analytes and ultrasonography. Recent advancements have resulted in the development of a noninvasive prenatal screening (NIPS) test that uses cell-free foetal DNA sequences isolated from a maternal blood sample. There is a discussion of those accomplishments.
... [2] It is one of the most leading causes of intellectual disability and millions of these patients face various health issues including learning and memory, congenital heart diseases(CHD), Alzheimer"s diseases (AD), leukemia, cancers and Hirschprung disease(HD).The incidence of trisomy is influenced by maternal age and differs in population (between 1 in 319 and 1 in 1000 live births). [3][4][5][6]Trisomic fetuses are at elevated risk of miscarriages and DS people have increased incidence of developing several medical conditions [7]. Recent advancement in medical treatment with social support has increased the life expectancy for DS population. ...
Article
Full-text available
Down syndrome (DS) is one of the commonest disorders with huge medical and social cost. DS is associated with number of phenotypes including congenital heart defects, leukemia; Alzheimer"s disease etc.DS individuals are affected by these phenotypes to a variable extent thus understanding the cause of this variation is a key challenge. In the present review article, we emphasize an types of Down syndrome, Genetics of DS, Epidemiology of DS, clinical features, screening and management and treatment of DS.Moreover, we have also reviewed various prenatal diagnostic method from karyotyping to rapid molecular methods-MLPA, FISH, QF-PCR, PSQ, NGS and noninvasive prenatal diagnosis. The scope of this article is firmly on providing the basic information in DS. The electronic database included Pub Med, Medline, Science Direct, Goggle Scholar using terms Down syndrome and trisomy 21. Relevant articles published in English on reference lists were identified and retrieved from electronic and print journals.
... Cel mai frecvent sindrom genetic prezent în studiu a fost sindromul Down, acesta fiind şi cea mai frecventă anomalie cromozomială genetică la nivel global [10][11][12]. Rezultatul este în concordanţă cu studiul realizat de Bermejo şi Martinez-Frias [13], unde numărul mare de anomalii oculare a fost datorat unui număr mare de cazuri de trisomie 21. ...
Article
Introducere. Anomaliile oculare congenitale minore (ACOM) constituie markeri importanţi în detectarea anumitor afecţiuni genetice. Aceştia sunt diverşi ca localizare, număr sau intensitate de exprimare, chiar în cadrul aceleiaşi afecţiuni. Identificarea lor şi, mai ales, interpretarea corectă a acestora sunt esenţiale pentru diagnosticarea precoce a unui pacient cu boală genetică. Scop. Scopul studiului este reprezentat de analiza ACOM în sindroamele genetice, prin identificarea principalelor morfotipuri de ACOM, precum şi analiza sindroamelor genetice care se asociază cu acestea. Material şi metodă. A fost realizat un studiu prospectiv pe un lot de 118 pacienţi în perioada februarie 2015 – februarie 2019 cu boli genetice care asociază şi AC oculare. S-a efectuat o examinare oftalmologică amănunţită atât la nivelul anexelor, cât şi la nivelul globului ocular. Rezultate. Din totalul de 118 pacienţi, 84 (71%) au prezentat malformaţii minore cu sau fără malformaţii majore asociate. Cele mai frecvente anomalii oculare minore au fost întâlnite la nivelul pleoapelor, irisului şi retinei, iar sindromul Down este cel mai frecvent asociat cu anomalii oculare minore. Concluzii. Anomaliile oculare congenitale minore, chiar dacă nu sunt de gravitate, constituie deseori elemente sugestive pentru anumite sindroame genetice. Indiferent de boala genetică, din punct de vedere anatomic, pleoapa a fost anexa globului ocular care ne-a oferit mereu indicii „minore“ cu un important răsunet diagnostic.
... The most common genetic syndrome present in the study was Down syndrome, which is also the most common genetic chromosomal abnormality, globally [10][11][12]. The result is consistent with the study conducted by Bermejo and Martinez-Frias [13], where the large number of ocular abnormalities was due to a large number of cases of trisomy 21. ...
Article
Introduction. Minor congenital ocular anomalies (MCOA) are important markers for the detection of certain genetic disorders. Even within the same disease, they can vary in their position, numbers or expression intensity. Early detection and diagnosis of genetic disorders are essential to find them and to interpret them correctly and quickly. Aim. The purpose of this study was to analyse MCOA in genetic diseases, to identify the main types of MCOA as well as to analyze associated genetic disorders. Material and methods. This is a prospective study of 118 cases presenting with genetic disorders that also presented with MCOA. Its duration was from February 2015 to February 2019. Detailed ocular and adnexa examinations were performed. Results. Of 118 patients who were enrolled in this study, 84 (71%) had minor ocular anomalies with or without associated major anomalies. Most common MCOA were identified in the eyelid, iris and retina. Down syndrome was the most frequent syndrome associated with MCOA. Conclusions. Minor congenital ocular abnormalities, even if they are not serious, are often suggestive of certain genetic syndromes. Regardless of the genetic disorders, anatomically, the eyelid is the ocular adnexa that always gives us minor clues of important diagnosis significance.
... In general, the overall incidence of Down's syndrome is 1/800 live births, which seems to increase remarkably to 1/400 in mothers above 35 years of age, and to 1/12 by the age of 50 [9]. ...
... In general, the overall incidence of Down's syndrome is 1/800 live births, which seems to increase remarkably to 1/400 in mothers above 35 years of age, and to 1/12 by the age of 50 [9]. ...
Article
Full-text available
Abstract Background: Down’s syndrome (DS) due to an extra chromosome 21 or a partial trisomy is the most common genetic cause of intellectual disability. The affected individuals usually present with characteristic clinical manifestations and are seen to be associated with various systemic defects. Objectives: The aim of our study was to observe the major congenital anomalies associated with Down’s syndrome in North Indian population. Material & Methods: Blood samples of 51 children (0-10 years) who were screened for suspicion of DS in Department of Paediatrics, KGMU, Lucknow, were collected and karyotyping was conducted in cytogenetic laboratory of the Department of Anatomy, King George’s Medical University (KGMU), Uttar Pradesh, Lucknow, India. Data was analysed using Statistical package for Social Science (SPSS) version 21.0. Result: 60% of the cases were found to be associated with at least one major congenital anomaly, of which cardiac anomalies were most common. Keywords. Down’s syndrome, disability, trisomy, anomalies, karyogram, cytogenetic.
... Even among developed countries the birth prevalence varies depending upon mean maternal age and practice of antenatal diagnosis of DS and termination of affected pregnancies. The birth prevalence of DS is 1 in 733 live births in the USA 5 , 1 in 449 in the United Arab Emirates (UAE) 6 and 1 in 300 in Pakistan. 7 Advanced maternal age at conception appears to be the major contributing factor for the increased incidence of DS in less developed countries like Pakistan and UAE. ...
Article
Full-text available
Yaqoob M, Manzoor J, Hyder SN, Sadiq M. Congenital heart disease and thyroid dysfunction in Down syndrome reported at Children`s Hospital, Lahore, Pakistan. Turk J Pediatr 2019; 61: 915-924. Down syndrome is one of the main causes of intellectual disability in children. It occurs in every community and ethnic group. Several co-morbid conditions are associated with this syndrome. The present study was conducted to determine the frequency of congenital heart disease and thyroid dysfunction in a group of children affected with this genetic disorder. It was a record based retrospective study. A child having specific clinical features and chromosomal analysis showing an extra chromosome 21 was diagnosed as having Down syndrome. Diagnosis of congenital heart disease was based upon results of echocardiography. Thyroid dysfunction was diagnosed when either or both tetraiodothyronine and thyroid-stimulating hormone serum levels were abnormal. Three hundred and fifty cases were enrolled in the study according to the preset criteria for Down syndrome. Two hundred and ten (60%) were males and 140 (40%) females showing male to female ratio as 1.5 to 1. Majority of the children (55.1%) presented between 7 months and 24 months of age. Congenital heart defects were found in 41.8% of the cases. Ventricular septal defect was the most common, 41%. Thyroid dysfunction was found in 22% (n=60) of the cases of which 5.9% (n=16) had hypothyroidism. In conclusion, the frequency of congenital heart disease and thyroid dysfunction in Down syndrome children is high. Early referral of these children to tertiary health care facilities is emphasized as timely detection and management of these comorbid conditions will help in reducing the morbidity and mortality in this group of children.
... 4,20,21,[24][25][26][27][28][29] Previously, various studies reported that the frequency of translocation was varied from 0.67% to 8.8% in Down syndrome, the lowest frequency was reported in UAE, Iran, and Malaysia and whereas the highest frequency was reported in India (8.8%). [30][31][32] ...
... In certain cases, such as the UAE, the state is actively involved in facilitating the use of material objects, technologies and artifacts to fulfill its policies and goals (105-106). For example, in health policy, to reduce the number of birth defects and disability resulting from consanguinity, the UAE has deployed mandatory pre-marital genetic screening for its citizens (Al-Gazali, Hamamy, and Al-Arrayad 2006; Murthy et al. 2007). In the areas of immigration and national security policy, the UAE uses sophisticated national ID cards with a photograph, digital signature, and fingerprint biometrics to facilitate the monitoring of foreign workers' residency permits (Al-Khouri 2012). ...
Article
Full-text available
Scholars of the global phenomenon of international student assessments (e.g., PISA, TIMSS) have paid little attention to the ways in which student users of these material objects are configured in nations that are located at the periphery of knowledge production. Our analysis takes the United Arab Emirates as its case study to capture the social construction processes and relations of PISA and TIMSS users, agents and test objects within global educational accountability infrastructures. Drawing on evidence collected from interviews with principals, vice principals and teachers in nine schools as well as with government officials, we reveal how the state plays a role in the re/configuration of the user in this process. We also trace the discursive and emotional narratives that delineate usage and the institutional practices deployed to solidify user re/configurations. We argue that user configurations induce institutional reforms, cognitive remappings, and affective reactions which reflect adaptations being made by ‘real’ users to misconfigured material objects. We suggest that rather than blaming students for their poor performance on global tests, it is more appropriate to point to a failure in the material object’s obdurate design and monocultural user configuration.
... Down syndrome is one of the most leading causes of intellectual disability and millions of these patients face various health issues including learning and memory, congenital heart diseases, Alzheimer's diseases, leukemia, cancers and Hirsch rung disease. The incidence of trisomy is influenced by maternal age and differs in population [5,6]. Facial findings in the patients can be characterised into extra oral and intraoral features (Table 1) [7]. ...
... The most common CHD phenotypes in DS patients are atrioventricular septal defects (AVSDs), ventricular septal defects (VSDs), Tetralogy of Fallot (TOF), and atrial septal defects (ASDs) and may differ with ethnicity [4][5][6][7][8]. Increased incidence of CHD in children with DS from certain population was reported to be associated with widespread consanguinity [9]. ...
Article
Full-text available
Down syndrome (DS) is the most common autosomal chromosome anomaly. DS is frequently associated with congenital heart disease (CHD). Patients with DS have 40–60% chance of having CHD. It means that CHD in DS is not only due to trisomy 21 and there are some other genetic factors underlying CHD in DS children. In this study, a total of 240 DNA samples from patients were analyzed including 100 patients with CHD only, 110 patients having CHD along with DS and 30 patients with isolated DS. A cardiovascular gene panel consisting of probes for 406 genes was used to screen DNA samples of all 240 patients for mutation identification. All variants were annotated and common variants were obtained. Briefly, 28 common variants (variants common in two or more than two individuals) were obtained in a group of samples containing DNA from DS patients having CHD as well, 63 variants were found to be unique to DS group of samples and 73 variants have been identified in patients with CHD only. In order to identify genomic variations determining the risk for CHD in DS, only those variants present in DS-CHD group and absent in isolated CHD and/or isolated DS group were considered for further analysis. Variants specific to DS-CHD group were further evaluated based on expression and function data and pathogenicity of the variant of interest. We have implicated mutations in GATA3, KCNH2, ENG, FLNA, and GUSB genes as an underlying risk factor for CHD in DS patients.
... Studying on 1760 affected persons and considering all their chromosomal abnormalities showed that 377 men (67/9%) and 178 women (32/1%) had chromosomal abnormality among them 5/7% had both reciprocal and Robertsonian translocations (18)(19)(20)(21)(22). Understand the main areas in chromosomes in terms of genotype and phenotype is very useful. Determining the karyotype of these critical areas and occasionally various congenital abnormalities we can see chromosomal abnormalities (23). The place of responsible genes in human abnormalities could be obtained from studying the effects of phenotype and chromosomal abnormalities. ...
Article
Full-text available
Introduction: Intellectual disability or intellectual retardation is a condition in which total mental functioning is distinctively below average and there are disabilities in adaptive behaviors during growth. According to the definition of American Mental Disability Community in 1992 a person is considered intellectually disabled if he or she has an IQ (intelligence quotient) of less than 70 and has a limitation in one or multiple adaptive skills. There are many different causes of intellectual disability that one of them is the genetically and chromosomal abnormalities. The aim of this paper was to study translocation breakout t (1; 4) (p21; p14) in a number of mental retardation patients in Iran. Materials and methods: This descriptive study was carried out on 100 persons with light mental disability by using cytogenetic methods. Lymphocytes were cultured in the dedicated environment by G-Banding karyotype of each person after obtaining patient’s blood sample. The data were statistically analyzed by logistic regression. Results: The findings showed that none of the patients with a mental disability was afflicted to the chromosomal translocation, (1; 4) (p21; p14). Conclusion: The lack of translocation in this study was equivalent with the obtained frequency in the same studies which have been carried out on the subjects suspected to have a translocation. Also, it seems that chromosomal analysis may be a usefulness diagnostic tool for children with mental retardation.
... Approximately 0.45% of human conceptions are trisomic for Hsa21 (1). The incidence of trisomy is influenced by maternal age and differs between populations (between 1 in 319 and 1 in 1000 live births are trisomic for Hsa21) (2)(3)(4)(5)(6). Trisomic fetuses are at an elevated risk of miscarriage, and people with DS have an increased risk of developing several medical conditions (7). ...
Article
Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and is associated with a number of deleterious phenotypes, including learning disability, heart defects, early-onset Alzheimer's disease and childhood leukaemia. Individuals with DS are affected by these phenotypes to a variable extent; understanding the cause of this variation is a key challenge. Here, we review recent research progress in DS, both in patients and relevant animal models. In particular, we highlight exciting advances in therapy to improve cognitive function in people with DS and the significant developments in understanding the gene content of Hsa21. Moreover, we discuss future research directions in light of new technologies. In particular, the use of chromosome engineering to generate new trisomic mouse models and large-scale studies of genotype-phenotype relationships in patients are likely to significantly contribute to the future understanding of DS.
... Prevalence of Congenital Heart Diseases (CHD) increased in the last 15 years, it was reported in Europe 8.2 per 1000 live birth [6]. The prevalence of CHD is about 40-50% in literatures (between 30-65%) in Down syndrome children [7,8], while it is between 40.9-86.8% in Saudi Arabia [9][10][11][12]. Atrio-ventricular septal defect (AVSD) is the most common cardiac anomalies associated with DS 54%, followed by ventricular septal defect (VSD), patent ductus arteriosus, and atrial septal defect (ASD) [7]. ...
... Sindrom Down (SD) merupakan kelainan kromosom yang ditandai dengan kelebihan satu kromosom 21. 1 Insiden penderita SD dilaporkan sekitar 1/300 sampai 1/1000 kelahiran, dimana kasus ini masih tinggi ditemukan di Finlandia 1/364 kelahiran, Dubai 1/449, dan Belanda 1/625. [2][3][4] Jumlah penderita SD di Indonesia belum didapatkan data secara pasti, namun dari data rekam medik di Central of Biomedical Research (CEBIOR) Fakultas Kedokteran Universitas Diponegoro, Semarang ditemukan sebanyak 123 penderita SD yang diperiksa kromosom selama tahun 2005 sampai 2010. ...
Article
Full-text available
AbstrakPenderita sindrom Down (SD) sering mengalami gangguan sistem imun, yangmenyebabkan kerentanan terhadap infeksi, tingginya angka kesakitan dan kematian.Polimorfisme gen TNF-α -308G>A berkaitan dengan peningkatan kerentanan terhadap infeksi.Tujuan penelitian ini adalah untuk mengetahui polimorfisme gen TNF-α -308G>A pada penderitaSD di Semarang. Penelitian ini merupakan penelitian deskriptif, dengan jumlah sampel 68orang (34 penderita SD dan 34 kontrol) yang ada di laboratorium CEBIOR. Pemeriksaanpolimorfisme gen ini dilakukan dengan menggunakan metode PCR-RFLP dan enzim retriksiNcoI serta dielektroporesis pada gel agarose 2%. Polimorfisme gen TNF-α -308G>A padapenderita SD didapatkan 4,4%, sedangkan pada kelompok kontrol 2,9%. Polimorfisme genTNF-α -308G>A pada penderita SD ditemukan di daerah ini lebih rendah dibandingkan dengantempat lain. Kemungkinan adanya perbedaan etnik mempengaruhi kejadian polimorfisme genTNF-α pada populasi di Indonesia dibandingkan dengan populasi di Caucasia.AbstractPeople with Down syndrome (DS) often have impaired immune system, which causessusceptibility to infection, morbidity and mortality. TNF-α -308G>A polymorphism was foundto be associated with the increase of susceptibility to infection. The aim of this research is todetermine the distribution and allele frequency of TNF-α -308G>A polymorphism among DSpatients in Semarang. This is a descriptive research with 68 subjects (34 DS patients and 34control groups) in the CEBIOR laboratory. The polymorphisms of genes were examined usingPCR-RFLP, NcoI restriction enzyme, and electrophoresis on 2% agarose gel. Polymorphismof TNF-α -308G>A was found 4,4% on the DS groups and 2,9% on the control group.Polymorphisms in gene TNF-α -308G>A found in DS was lower in this area compared toother area. The difference in the ethnic background might be a well plausible explanation forthe differentiation between polymorphisms on TNF-α in Indonesian population compared toCaucasian population.
... Approximately 0.45% of human conceptions are trisomic for Hsa21 [1]. The incidence of trisomy is influenced by maternal age and differs among populations (between 1 in 319 and 1 in 1000 live births are trisomic for Hsa21) [2][3][4]. Trisomicfetuses are at an elevated risk of miscarriage, and people with DS have an increased risk of developing several medical conditions [5]. Recent advances in medical treatment and social inclusion have significantly increased the life expectancy of people with DS: in economically developed countries, the average life span of people who are trisomic for Hsa21 is now greater than 55 years [6]. ...
Article
Down Syndrome (DS) has a significant impact on the development of many tissues, most notably in the heart and in the brain. According to the clinical need to better investigate these aspects, the main aim of this study was to make an overview on the cardiac features in adult individuals with DS. The following data of 37 individuals with DS (range: 18-60 years) were collected and analysed: age, gender, height, weight, waist to height ratio (WHER), smoking history and cardiac parameters (heart rate and blood pressure), blood glucose level or glycaemia, cholesterol (total, high-density lipoprotein - HDL - and low-density lipoprotein - LDL - cholesterol) and triglycerides. In addition, their gait pattern were quantified with 3D Gait Analysis. BMI, WHER and cholesterol HDL results were above the upper limits of the recommended range in people with DS; on the contrary, blood pressure, heart rate, glycaemia, cholesterol-LDL and triglycerides were within the recommended range. Comparing males and females in the DS group, the females showed statistically different values for cholesteroltotal, and triglycerides values, with lower values in comparison to males. In motor performance, people with DS presented abnormal gait patterns. Some significant correlations were found: age with LDL, WHER with weight and BMI, systolic with diastolic blood pressure, total cholesterol with LDL and triglycerides. Our results showed that adults with DS suffer from a high prevalence of physical disorders, including overweight and obesity, and abnormal cholesterol values, together with abnormal gait pattern.
... own syndrome (DS) is the most frequently occurring chromosomal abnormality in humans and affecting between 1 in 400-1500 babies born in different populations, depending on maternal age, and prenatal screening schedules (1)(2)(3)(4)(5)(6). DS is the common genetic cause of intellectual disabilities worldwide and large numbers of patients throughout the world encounter various additional health issues, including heart defects, hematopoietic disorders and early-onset Alzheimer disease (7)(8)(9). ...
Article
Full-text available
Down syndrome (DS) is a birth defect with huge medical and social costs, caused by trisomy of whole or part of chromosome 21. It is the most prevalent genetic disease worldwide and the common genetic cause of intellectual disabilities appearing in about 1 in 400-1500 newborns. Although the syndrome had been described thousands of years before, it was named after John Langdon Down who described its clinical description in 1866. Scientists have identified candidate genes that are involved in the formation of specific DS features. These advances in turn may help to develop targeted therapy for persons with trisomy 21. Screening for DS is an important part of routine prenatal care. Until recently, noninvasive screening for aneuploidy depends on the measurement of maternal serum analytes and ultrasonography. More recent progress has resulted in the development of noninvasive prenatal screening (NIPS) test using cell-free fetal DNA sequences isolated from a maternal blood sample. A review on those achievements is discussed. Key
... 28 The incidence of DS per live births varies across countries and the estimates for some countries are outlined in Table 1. 36,37,38,39,40,41,42 Characteristic physical and health implications of Down syndrome DS is a multisystem disorder that affects the individual physically, medically and psychologically. The physical -head, face and neck -features 2,5,15 include brachycephaly (disproportionately shorter or small head or skull shape), unusually round face, short neck, low-set, small ears, flat nasal bridge, microgenia (an abnormally small chin), macroglossia (protruding or oversized tongue) due to small oral cavity, small chin, almond shape to the eyes caused by an epicanthic fold of the eyelid and oblique palpebral fissures. ...
Article
Full-text available
Optometrists as primary eye care providers examine patients from diverse populations, including those with special needs such as Down syndrome. Down syndrome is a chromosomal abnormality associated with several health conditions including vision anomalies such as refractive, accommodative and vergence anomalies, as well as ocular pathology. In this article, a narrative review of Down syndrome including the background, historical perspective, aetiology and genetic mechanisms, types, epidemiology, as well as the physical and medical profile of Down syndrome is presented.Keywords: Down syndrome review; Trisomy 21; historical perspective; etiology; types and epidemiology; features; Optometrist
... The association of translocations with poor obstetric history, fertility failure, amenorrhea, ambiguous genitalia and ID with MCA or DS has been well documented by various researchers. 20,21 Clinically, the most important single Robertsonian translocation involves chromosomes 14 and 21 (detected in two patients in this study); 4.0% of patients with DS are associated with this translocation. ...
Article
Full-text available
Introduction: Chromosomal abnormalities are a major etiology of intellectual disability (ID) and multiple congenital anomalies (MCAs). Screening for chromosomal aberrations by clinical diagnostic techniques has been primarily performed through standard karyotyping. Methods: A cytogenetic study involving 1730 individuals with ID and/or MCA was conducted using lymphocyte culture and high-resolution G-banding method. Results: Various types of chromosomal abnormalities were detected in 440 patients (25.5%). Numerical and structural chromosomal abnormalities, respectively, were observed in 63.3% (278 out of 440) and 36.7% (162 out of 440) patients. Among the chromosomal abnormalities, sexual chromosomal abnormalities were found in some cases, and Klinefelter syndrome with 2.5% frequency was the most frequent sex chromosomal abnormality. Autosomal abnormalities were found in cases, and Down syndrome was the most frequent autosomal chromosomal abnormality occurring in 41.0% of detected abnormalities. Conclusion: The higher contribution of chromosome aberrations in the northwest of Iran indicates the importance of cytogenetic evaluation in the etiology of MCA and/or ID patients. Genetic counseling was provided to the family members to explain the recurrence risk as well as the need for prenatal diagnosis in subsequent pregnancies and management of patients by collected data bank.
... Only 5 families had 5 th , 6 th , and 7 th order of DS child (Table 5). On the contrary, a study in UAE reported that a child with DS was mostly last or second last child (Murthy et al. 2007). Some reports suggest that risk of DS increases with increased parity in both young and old mothers (Cutler et al. 1986;Doria-Rose et al. 2003) while Chan et al. (1998) contradict this observation. ...
Article
Full-text available
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.
... The mean maternal age was 33.48 years and about 41.66% of the mothers were above 35 years old. The trend of increasing incidence of DS is thought to result from advanced maternal age and high parity [92]. ...
Chapter
Down syndrome (DS) is the commonest chromosomal disorders in the world; affecting all countries, all races, and both sexes. It was identified since premodern art and middle ages. The risk for DS births is multi-factorial and includes both genetic and environmental factors. The prevalence of DS could be affected by different factors including distribution of maternal age in the population, adequacy and completeness of ascertainment, accurateness of diagnosis, level of selective prenatal termination of affected pregnancies, as well as different unrecognized genetic and environmental factors. Incidence of DS is expected to be significantly high in the developing countries, probably due to the higher death rate from comorbidities in DS such as congenital cardiovascular defects. Improving survival of infants with DS because of better care especially of cardiovascular malformations will affect prevalence rather than the incidence of DS. According to World Health Organization; the predictable incidence of DS is between 1 in 1,000 to 1 in 1,100 live births all over the world. The difference in prevalence among populations or countries or in the same population over time will depend on the potential risk factors in common for that community.
... Down syndrome is one of the most leading causes of intellectual disability and millions of these patients face various health issues including learning and memory, congenital heart diseases(CHD), Alzheimer's diseases (AD), leukemia, cancers and Hirschprung disease(HD). The incidence of trisomy is influenced by maternal age and differs in population (between 1 in 319 and 1 in 1000 live births) [1][2][3][4][5]. DS has high genetic complexity and phenotype variability [6][7][8]. ...
Article
Full-text available
Down syndrome (DS) is one of the commonest disorders with huge medical and social cost. DS is associated with number of phenotypes including congenital heart defects, leukemia, Alzeihmer's disease, Hirschsprung disease etc. DS individuals are affected by these phenotypes to a variable extent thus understanding the cause of this variation is a key challenge. In the present review article, we emphasize an overview of DS, DS-associated phenotypes diagnosis and management of the disease. The genes or miRNA involved in Down syndrome associated Alzheimer's disease, congenital heart defects (AVSD), leukemia including AMKL and ALL, hypertension and Hirschprung disease are discussed in this article. Moreover, we have also reviewed various prenatal diagnostic method from karyotyping to rapid molecular methods - MLPA, FISH, QF-PCR, PSQ, NGS and noninvasive prenatal diagnosis in detail.
Article
Full-text available
Down syndrome is the most common genetically mediated intellectual disability. Although many physiologic and pathologic features of Down syndrome are discussed at length in the literature, the ocular manifestations of Down syndrome have seldom been discussed in a comprehensive fashion. Given that Down syndrome has ocular manifestations from the front to the back of the eye, it is important for physicians to become familiar with these manifestations, especially given the prevalence of Down syndrome. This review aims to discuss the varied ophthalmologic manifestations of Down syndrome – including strabismus, amblyopia, nystagmus, accommodation deficits, nasolacrimal duct obstruction, keratoconus, optic nerve pathology, neoplastic disease, and retinal pathology – to facilitate better care and visual outcomes in this important patient population.
Article
Trisomy 21 is a common birth defect in humans. Screening for trisomy 21 is one of the most important tasks in routine prenatal care and robust noninvasive diagnostics are needed in clinical practice. Urinary proteomics offers a new research platform for diagnostics innovation in this context. We report here new biomarker candidates using urinary proteomics profiling. Specifically, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the proteomes of urine samples from 19 pregnant women (aged 28-44 years) carrying fetuses with trisomy 21 and 22 healthy pregnant women (aged 27-42 years) carrying fetuses with normal karyotype. We identified more than 50 differentially expressed proteins between the trisomy 21 group and healthy group, and most of these proteins were associated with the embryonic development. Importantly, tissue inhibitor of metalloproteinases 2 (TIMP2) and lysosomal-associated membrane protein 2 (LAMP2) were further selected as potential urinary protein biomarkers. We found that the combination of TIMP2 and LAMP2 could differentiate fetuses with trisomy 21 from healthy controls with a sensitivity of 74%, a specificity of 82%, and an area under the receiver operating characteristic curves (AUC) value of 0.82 (95% confidence interval, 0.69-0.95). We conclude that TIMP2 and LAMP2 offer promise as biomarker candidates and warrant further clinical research in larger study samples. These findings further our understanding of the pathological processes involved in fetal trisomy 21 and are poised to accelerate the development of new noninvasive potential biomarkers for trisomy 21 prenatal screening.
Article
Full-text available
Down syndrome is one of the most leading causes of intellectual disability and millions of these patients face various health issues including learning and memory, congenital heart diseases (CHD), Alzheimer's diseases (AD), leukemia, cancers and Hirschprung disease (HD). The incidence of trisomy is influenced by maternal age and differs in population (between 1 in 319 and 1 in 1000 live births) [1]. DS has high genetic complexity and phenotype variability. Trisomic fetuses are at elevated risk of miscarriages and DS people have increased incidence of developing several medical conditions [2,3]. Recent advancement in medical treatment with social support has increased the life expectancy for DS population. In developed countries, the average life span for DS population is 55 years [4].
Article
Full-text available
I draw on the United Nations Convention on the Rights of Persons with Disabilities as a human rights model of disability to analyze how the United Arab Emirates (UAE) is meeting its obligations toward disabled people in higher education and employment. This paper argues that institutions in the Emirate of Abu Dhabi adopted a paternalistic and reactive approach to address the rights of disabled people. Drawing on the experiences of disabled people in the UAE and evidence from interviews conducted from 2016 to 2018, the analysis identifies several key challenges to inclusion that stem from a weak enforcement and accountability framework, which results in a lack of accessibility measures and supports in university and workplace settings. The paper recommends interventions that would create an institutional environment where disabled people are treated as rights holders and given equal and equitable access to higher education and employment. • Points of interest • This paper studies the barriers that disabled people face in higher education and employment in the United Arab Emirates (UAE). • The UAE is a very rich oil-producing country located in the Arabian Gulf with a small number of citizens and a large migrant population. • The key problems disabled people talked about are how they are denied equal access to learning supports in the university and how employers do not give them measures and tools to do their work. • Because the UAE has signed the United Nations Convention on the Rights of Persons with Disabilities (CRPD), it should not allow that disabled people are treated unfairly or that they are treated in an unequal way. • The UAE should make its laws stronger and monitor the implementation of the CRPD.
Article
Full-text available
Obesity may affect the respiratory functions in many ways. The adipose tissue deposited around the rib cage, abdomen and visceral cavity affects work of breathing and reduces the pulmonary functions. There are different tests to measure lung function or pulmonary function known as pulmonary function tests. To determine the relation between body mass index and lung functions in obese and overweight children with Down syndrome. A cross-sectional study design was directed to 30 normal children and 60 chil¬dren with Down syndrome (30 with obesity and 30 with overweight range), aged 7-9 years. Body mass index and lung function (spirometry) were evaluated. There was no sig¬nificant differences between groups concerning the reference values of lung functions. Moreover, there was a negative correlation between BMI and lung functions in the selected age group children with Down syndrome. Overweight and obese children with Down syndrome demonstrated similar values of lung volume and capacity as normal children. Thus, anthropometric measures and body composition characteristics may not be prognostic features for changed lung function.
Thesis
La trisomie 21 (T21) résulte de la présence d’une extra-copie du chromosome 21 (Chr21). Parmi les gènes candidats impliqués dans les déficits cognitifs liés à la T21, DYRK1A est un des plus pertinents. Des études ont montré une corrélation entre l’augmentation de son activité kinase avec les déficits mnésiques observés dans les modèles murins de T21. Afin de comprendre les mécanismes sous-jacents aux altérations cognitives causées par son surdosage, nous avons utilisé des modèles murins sur-exprimant DYRK1A seule ou en plus d’autres gènes orthologues au Chr21, ainsi que des inhibiteurs spécifiques de DYRK1A (Leucettines) synthétisés par ManRos Therapeutics. Ici sont présentées les conséquences d’un traitement chronique avec ces Leucettines sur la cognition de ces animaux. Des analyses du phosphoprotéome de ces souris traitées ou non avec une des Leucettines, la L41, a mis en lumière des cibles et mécanismes biologiques impliqués dans les perturbations mnésiques de ces animaux. Enfin, ce projet a surtout permis de mettre en évidence un nouvel inhibiteur plus sélectif pour DYRK1A comme candidat-médicament pour l’amélioration des fonctions cognitives des porteurs de la T21.
Chapter
Copy number variation (CNV) reflects a gain or loss in the number of copies of DNA fragments in a genome. CNV is common in genetic diseases and is known to cause particular neurodegenerative diseases. We developed a dNTP-limited, competitive PCR technique to identify relative copy number differences between a reference and one or more target genes. Suitable fragments with single melting domains, well-separated melting temperatures, and no common homologs were identified by uMelt melting curve prediction software. Relative product amounts were maintained during multiplex PCR into the plateau phase by limiting dNTPs. After PCR, fluorescent melting curve analysis was automatically performed with the saturating DNA dye, LCGreen® Plus. Exponential background was removed, melting curves were plotted as negative derivative melting peaks, and the reference peak was normalized by both position (temperature) and height of each peak. With the reference peak normalized, the height of the target peaks established the copy number order that can be quantified against standards. Using chromosome X variation, the best dNTP concentration to distinguish copy numbers was about 6 μM each and CVs of about 1% were obtained with high-resolution melting analysis. The method was applied to spinal muscular atrophy, trisomies 13, 18, and 21, and cystic fibrosis gene deletions. The method is rapid, economical, and closed tube, and can be used for diagnosis or confirmation of copy number differences identified by high-throughput screening methods.
Article
Children with Down syndrome (DS) have wide range of respiratory problems. Although underlying abnormalities in the respiratory system are important causes of morbidity and mortality in children with DS, particularly in the young, abnormalities in other organ systems may also impact respiratory function. A comprehensive evaluation of the child with DS and respiratory disease may prevent short-term morbidity and mortality, and reduce the incidence of complications in the long term. This review provides an overview of the various causes of respiratory disease, and insight into some of the newer therapies available to treat obstructive sleep apnea, in this population.
Article
INTRODUCTION: Down syndrome is a genetic disease due to chromosomal aberration. Although it is still a health problem with a great social and family impact, the family is considerably misinformed about important elements and there are different criteria about the possibilities and achievements of these children. OBJECTIVE: to determine the knowledge of the parents about the evolution and future possibilities of the children carriers of this genetic disease, the difficulties of the neuropsychomotor development and the different types of disability. METHODS: a quasiexperimental interventional research with a before-after study design was conducted in a non-equivalent group at "Zunzún" Special Day Care Centre, in Playa municipality, Havana City, from March to June, 2007. The universe was composed of all the mothers or fathers of the children with Down syndrome enrolled in this institution. The sample consisted of all the mothers or fathers of the children of the universe. There were 34 mothers and 4 fathers that lived in various municipalities of Havana City. The research had 3 stages and 3 workshops were conducted. The data obtained were tabulated by the simple count method and they were expressed in percentages and reflected in tables. RESULTS: before the workshops the parents recognized the disabilities in their children. The most frequent were speech disorders, difficulties in self-validism and to obey orders, and to believe in the possibility of the reintegration to society. After the workshops, the recognition of these incapacities, as well as the need to receive information to encourage the child, and the parents' hope in their children increased. CONCLUSIONS: the workshops conducted proved to be effective to improve the knowledge and education of parents about the disease, and the parents' expectations in the future of their children rose.
Chapter
The United Arab Emirates (UAE) was founded in 1971 as a federation of seven emirates on the Arabian Gulf. It is bounded by Qatar on the northwest, Saudi Arabia on the west and southwest, Oman on the east and northeast, and the Arabian Gulf on the north. It occupies an area of 83,600 km2 and Abu Dhabi is the capital of the state. Six of the emirates lie on the southern shore of the Arabian Gulf and present a continuous coastline stretching some 600 km. The six emirates in geographical order from west to east are Abu Dhabi (which comprises 87% of the entire area of the UAE), Dubai, Sharjah, Ajman, Um Al-Quween, and Ras Al Khaimah. Fujairah is the only emirate without a coastline on the Arabian Gulf; it lies entirely on the Gulf of Oman. © Springer-Verlag Berlin Heidelberg 2010. All rights are reserved.
Article
Full-text available
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.
Article
Objectives: This study aimed to define the incidence of Down's syndrome and to describe the epidemiology of cardiac lesions in Jamaican children with Down's syndrome. Methods: A prospective study was conducted on 53 infants during the period January 1, 2007 to December 31, 2007, at the Bustamante Hospital for Children, Kingston, Jamaica. A medical history, physical examination and echo Doppler was performed on each child. Results: Forty-six thousand babies were born in Jamaica in 2007, of which 53 infants were diagnosed with Down's syndrome, giving an incidence of 1:868. Forty-two (79.2%) infants had congenital heart lesions. Of the 42 patients with cardiac lesions, 50% had an isolated cardiac lesion while 50% had multiple defects. The most common single defect was the atrioventricular septal defect found in 10 (24%) patients. The most frequent concomitant malformation was a patent ductus arteriosus, found in 16 (38.1%) of the patients. The median age of diagnosis with Down's syndrome was 0.14 weeks (interquartile range (IQR) 0 to 68 weeks). The median age of diagnosis with the cardiac lesion was 15.1 weeks (IQR 0 to 40.0 weeks). Conclusions: The incidence of Down's syndrome in Jamaica is similar to the reported international experience. The distribution of cardiac malformations is similar to other countries; however, the main difference is the higher incidence of congenital heart disease and a higher incidence of combined lesions.
Article
Congenital Heart Diseases (CHDs) occur in about 40-50% of neonates born with Down syndrome. Increased incidence of CHDs in children with Down syndrome in certain populations has been associated with widespread consanguinity. Up till now there is no explanation for why some Down syndrome patients are susceptible to CHDs. This study aims to evaluate the frequency and patterns of CHDs in Down syndrome children at Almadina province in the west of Saudi Arabia and compare it with other previously reported studies. The study included Down syndrome children referred to the pediatric cardiology clinic for screening of CHDs. Full history taking, pedigree analysis and clinical examination were done to all cases. Parental consanguinity was documented and echocardiography was done to assess the cardiac lesions. Out of 110 Down syndrome children, 45 (40.9%) had CHDs were selected. Parental consanguinity was present in 26/45 (57.8%). The most frequent lesion was AVSD (33.3%), followed by VSD (22.2%), then ASD (13.3%), PDA was present in 8.8% and TOF was diagnosed in one case. The most common combination of cardiac lesions in Down syndrome cases included in this study was ASD with VSD. Conclusion: The frequency of CHDs in Down syndrome children from Almadina province in the west of Saudi Arabia was similar to those reported worldwide. The most frequent lesion diagnosed in this study was AVSD. The CHDs were slightly more frequent in Down syndrome children born to consanguineous parents.
Article
It is estimated that 5.3% of newborns will suffer from a genetic disorder, when followed up until the age of 25 years. In developing, as compared to western countries, hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency have a higher incidence due to severe falciparum malaria in the distant past, and autosomal recessive disorders have a higher frequency due to greater proportion of consanguineous marriages. Chromosomal disorders have a combined frequency of 1 in 153 births, therefore screening for chromosomal disorders is essential, using biochemical markers, ultrasonography, and recently by non-invasive prenatal diagnosis based on cell-free fetal DNA in maternal plasma. Preconceptional counseling should be encouraged. For genetic disorders screening should be carried out, ideally after marriage, but before pregnancy. The disorders to be screened depend upon ethnicity. Metabolic disorders have a high incidence in developing countries due to greater rate of consanguineous marriages. Newborn screening is recommended to reduce the burden of these disorders, as many metabolic disorders can be treated. Hearing and critical congenital heart disease should both be screened in the newborn period. Copyright © 2015 Elsevier Ltd. All rights reserved.
Article
Full-text available
Forensic dentistry is one of the most reliable methods used in human identification when other technique as fingerprint, DNA, visual identification cannot be used. Genetic disorders have several manifestations that can target the intra-oral cavity, the cranio-facial area or any location in the human body. A literature search of the scientific database (Medline and Science Direct) for the years 1990 to 2014 was carried out to find out all the available papers that indicate oral, cranio-facial signs, genetic and human identification. A table with 10 genetic conditions was described with oral and cranio-facial signs that can help forensic specialist in human identification. This review showed a correlation between genetics, facial and intra-oral signs that would help forensic ondontologist in the identification procedures.
Article
Full-text available
Objective: One hundred and seventy-seven newborn babies with chromosomal abnormalities were studied at the Al-Jahra satellite clinic of the Kuwait Medical Genetics Centre (KMGC), Kuwait, over a 7-year period from January 1983 to December 1989 to make a reanalysis and recomputation of the statistical results of the previous short-term studies. Methods: The data were collected from the registry of chromosomal abnormalities and from the clinical records of the patients in KMGC retrospectively. Controls were selected from the newborn babies delivered in the same period of study. The logistic regression analysis was computed using dependent/independent variables. Results: Ninety-five percent of the cases had numerical chromosomal abnormalities, and 5&percnt; had structural chromosomal abnormalities. One hundred and forty-five cases had classic trisomy 21, with an incidence of 2.9/1,000 live births (LB), 16 cases had trisomy 18 (0.3/1,000 LB), 5 cases had trisomy 13 (0.1/1,000 LB), 1 case had triploidy 69, XXY (0.02/1,000 LB) and 1 had Turner’s syndrome (0.05/1,000 female LB). Nine cases with structural chromosomal abnormalities were enumerated, dir dup(1) (p21–p32), del(1)(q32–q42), del(13)(q22–q34) and inversion Y chromosome, the incidence was 0.02/1,000 LB for each. Two cases of translocation trisomy 21 (0.04/1,000 LB) and 3 cases of cri-du-chat (0.06/1,000 LB) were enumerated too. Bedouins had a double-fold increased risk of trisomy 21 (odds ratio = 1.819, p = 0.032), and advanced maternal age was also a risk factor while paternal age showed inconsistent pattern of risk. Conclusion: This study confirmed the high incidence of the common trisomies and the role of advanced maternal age and the Bedouin ethnicity as a risk factor.
Article
Full-text available
Two young, unrelated multiplex families with Bedouin ancestors, each confirmed to have 3 sibs with recurrent regular trisomy-21 are reported. Low grade mosaicism for trisomy-21 (3/350 cells) was confirmed in the mother in one of the families but not in the other. However, two of the relatives (first degree) were confirmed to have Down syndrome. The recurrence risk for trisomy-21 based on livebirth and prenatal diagnosis data were estimated at 1 to 2 percent for couples 35 years old or younger at the time of conception. However, such risk estimates are not available for recurrence of simple trisomy-21 to a particular couple (<35 years). Clustering of trisomy-21, trisomy-18 has been reported among Bedouins. The possibility of cryptic parental mosaicism as well as should be considered in genetic counselling of families with sibships of regular trisomy-21 or other aneuploidy.
Article
Full-text available
Objective: To investigate the role of a patent foramen ovale in the pathogenesis of multiple brain lesions acquired by sport divers in the absence of reported decompression symptoms. Design: Prospective double blind cohort study. Setting: Diving clubs around Heidelberg and departments of neuroradiology and neurology. Subjects: 87 sport divers with a minimum of 160 scuba dives (dives with self contained underwater breathing apparatus). Main outcome measures: Presence of multiple brain lesions visualised by cranial magnetic resonance imaging and presence and size of patent foramen ovale as documented by echocontrast transcranial Doppler ultrasonography. Results: 25 subjects were found to have a right-to-left shunt, 13 with a patent foramen ovale of high haemodynamic relevance. A total of 41 brain lesions were detected in 11 divers. There were seven brain lesions in seven divers without a right-to-left shunt and 34 lesions in four divers with a right-to-left shunt. Multiple brain lesions occurred exclusively in three divers with a large patent foramen ovale (P = 0.004). Conclusions: Multiple brain lesions in sport divers were associated with presence of a large patent foramen ovale. This association suggests paradoxical gas embolism as the pathological mechanism. A patent foramen ovale of high haemodynamic relevance seems to be an important risk factor for developing multiple brain lesions in sport divers.
Article
Full-text available
The increased risk of Down's syndrome with maternal age underlies the recommendation for older pregnant women to be offered screening by amniocentesis or chorionic villus sampling. Recently Schimmel et al suggested that increased parity was an independent risk factor for Down's syndrome, but their study was not population based and did not include terminations of pregnancy.1 Using statewide statistics on births and terminations of pregnancy we investigated whether the risk of Down's syndrome is increased independently of maternal age by maternal parity, gravidity, or previous miscarriage. South Australia has around 20 000 births annually. The state collects data on birth defects that include maternal characteristics in both its perinatal and abortion statistics. These statutory collections are complemented by notifications from health professionals to the South Australian Birth Defects Register of defects in children detected within the first 5 years of life and by cytogenetic and necropsy reports. Each case of Down's syndrome included in these collections has been cytogenetically confirmed. …
Article
Full-text available
Reported livebirth prevalence of Down syndrome (DS) may be affected by the maternal age distribution of the population, completeness of ascertainment, accuracy of diagnosis, extent of selective prenatal termination of affected pregnancies, and as yet unidentified genetic and environmental factors. To search for evidence of the latter, we reviewed all published reports in which it was possible to adjust both for effects of maternal age and for selective termination (where relevant). We constructed indices that allowed direct comparisons of prevalence rates after standardising for maternal age. Reference rates were derived from studies previously identified as having near complete ascertainment. An index value significantly different from 1 may result from random fluctuations, as well as from variations in the factors listed above. We found 49 population groups for which an index could be calculated. Methodological descriptions suggested that low values could often be attributed to under-ascertainment. A possible exception concerned African-American groups, though even among these most acceptable studies were compatible with an index value of 1. As we have reported elsewhere, there was also a suggestive increase in rates among US residents of Mexican or Central American origin. Nevertheless, our results suggest that "real" variation between population groups reported to date probably amounts to no more than +/-25%. However, reliable data in many human populations are lacking including, surprisingly, some jurisdictions with relatively advanced health care systems. We suggest that future reports of DS livebirth prevalence should routinely present data that allow calculation of an index standardised for maternal age and adjusted for elective prenatal terminations.
Article
Full-text available
During 1992-2001, 673 Down syndrome patients were referred to the Department of Human Genetics in Alexandria. Regular (free) trisomy 21 constituted 95.4% of cases; Robertsonian translocation 2.7%; and mosaicism 0.7%. In 8 cases, regular trisomy 21 was associated with structural or numerical chromosome anomalies. Translocation was parentally inherited for 33.3% of cases and maternal transmission was twice as common as paternal. Two translocated Down syndrome fetuses were diagnosed prenatally in a t(14;21) carrier mother. Mean maternal age was high in regular trisomy 21 (38.2 years) but not in translocation (25.3 years). There was an excess of males in all groups except the mosaic group where the male:female ratio was 0.67. Cytogenetic investigations assist in patient management and family counselling.
Article
A study has been carried out in Riyadh to determine the incidence and distribution of Down’s syndrome births during a 9-year period from July 1982 to June 1991. Down’s syndrome was ascertained in 42 (23 females and 19 males) of 23,261 consecutive babies born alive to Saudi women, giving an incidence of 1 in 554 live births (1.8 per 1,000). A trend towards an increased incidence of Down’s syndrome with advanced maternal age or increased maternal parity was found. Cytogenetic studies were performed on 37 cases of which all but 1 were non-disjunction trisomy 21, while the remaining infant had a translocation. This study provides the first step for further epidemiological surveys of Down’s syndrome in the Kingdom of Saudi Arabia in order to prepare the ground for an effective antenatal screening programme for chromosomal disorders.
Article
Despite the clinical importance of trisomy 21, we have been ignorant of the causes of meiotic nondisjunction of chromosome 21. Recently, however, genetic mapping studies of trisomy 21 families have led to the identification of the first molecular correlate of human nondisjunction; i.e. altered levels and positioning of meiotic recombinational events. Specifically, increases in 0 exchange events or in distal-only or pericentromeric exchanges are significantly increased in trisomy 21-generating meioses. These observations have led to the idea that chromosome 21 nondisjunction requires ‘two hits’: first, the establishment in prophase I of a ‘vulnerable’ bivalent and second, abnormal processing of the bivalent at metaphase I or II.
Article
The frequency of Down syndrome in Libya was 1 in 516 live births. The mean age of Down mother was 35.62 years. Eighty two percent of the Down mothers were over 30 years of age as compared to 36% of the control Libyan mothers. As there was a greater percentage of late conceptions, the maternal age appears to be influential in the birth of Down syndrome in Libya. Cytogenetically 96% of the cases were that of trisomy 21. There was one case each of mosaic and 21/21 translocation, and four cases of 14/21 translocation as evidenced by Giemsa banding. Twenty two percent of the cases of Down syndrome also had other associated congenital abnormalities. The unique features involved in genetic counselling in this population are discussed. This study reflects the enormous problem of Down syndrome in the Arab world.
Article
By comparison with a more general theory, data on trisomy in live births, amniocenteses, and spontaneous abortions by year of maternal age are shown to fit a logistic augmented by a proportion independent of maternal age. The frequency of trisomy increases monotonically, with no discrepancy at extremely low or high maternal age. Trisomy 16 is exceptional in that all cases appear to be age-dependent. For groups A, B, and C most trisomies arise by a process independent of maternal age. A small proportion of these trisomies and about half of trisomies for smaller chromosomes (excluding trisomies 16 and perhaps 22) originate by some process dependent on maternal (but not paternal) age and therefore presumably independent of crossingover, which in the female takes place before birth.
Article
The effect of maternal age on the incidence of chromosomally normal spontaneous abortion and different categories of chromosome abnormality among all clinically recognized human pregnancies was evaluated. The results provide no evidence for a significant association of age with sex chromosome monosomy or polyploidy, but clearly demonstrate an effect of age on the frequency of trisomy and chromosomally normal spontaneous abortions. Estimated maternal age-specific rates of trisomy among all recognized pregnancies were calculated and suggest that a majority of oocytes of women aged 40 years and older may be aneuploid.
Article
Precision and accuracy in determining rates of Down syndrome at livebirth are indispensible to algorithms which determine eligibility for prenatal cytogenetic diagnostic services. We derived Down syndrome rates by single year of maternal age which we propose as a revised rate schedule for background risk. Data on European-origin populations were obtained from 5 sources judged most likely to have complete ascertainment of cases. A "constant plus exponent" regression model and variants extending the analysis to higher powers of maternal age were applied to several ranges of maternal age. Confidence intervals about the rates were calculated. This analysis results in rates significantly higher than those in widespread use though the confidence intervals show a need for caution in assuming precision. Sources of variation in rates are also considered.
Article
Previous studies have suggested a positive correlation between grand multiparity and the incidence of Down syndrome (DS). In order to study different parities as risk factors for DS, the Swedish health registries were used, and 2,615 infants with Down syndrome were selected from 2,184,590 infants born in 1973-1993. A statistically significant risk decrease for primiparas, and a significant risk increase for grand multiparas (5+), was found (age-adjusted odds ratios: 0.87 (95% CI: 0.80-0.96) and 1.40 (95% CI: 1.18-1.65), respectively. Potential confounders, such as the effect of truncated maternal 1-year age classes, citizenship, socioeconomic level, etc., were evaluated but were found to have only marginal effects. Evidence suggesting that the extension of prenatal diagnosis during the study period has decreased the incidence of DS among women of parity 1-4, but not among women of parity 5+, was found. The hypothesis that Swedish grand multiparas may have another attitude toward prenatal diagnosis than women of lower parities was confirmed when, in a data set containing information on 872 amniocenteses, a significantly lower rate of grand multiparity than expected was found. For the negative association between primiparity and DS, no obvious confounder was found.
Article
Life expectancy for persons with Down syndrome has increased dramatically throughout the world over the last 50 years. In 1978 the Israel Ministry of Health initiated a national program for the prevention of birth defects, and since 1979 data on the incidence and mortality of persons with Down syndrome have been collected and analyzed. Data from this register are presented for the period 1979-97 and compared to a previous study from Jerusalem for the period 1964-70. The actual incidence rate in 1997 was 1.1 per 1,000, but the total or true incidence rate (both live births and terminated pregnancies) was 2.32, which was not much different from the 1964-70 rate of 2.43. With regard to mortality, in 1979 45.9% of the children born with Down syndrome died before the end of the first year; in 1996 only 8.6% died. In 1979 57.8% died before the age of 14, compared to only 10.5% in 1996.
Article
To provide data on the cytogenetics and epidemiology of Down syndrome in our community. All cases of Down syndrome diagnosed cytogenetically were entered over a period of 5 years together with data regarding age at referral, parental ages and parity. A total of 280 cases were entered. In postnatal cases, the mean maternal age was 32.19 years and 41.5% of mothers were over 35 years. Only 47.3% of Down syndrome children were diagnosed at less than 1 month of age. The male to female sex ratio of 1.66 is significantly more elevated than that reported in larger registers. Because of problems inherent to Lebanon, this register does not have a high level of ascertainment, however it appears that the emphasis in a potential prevention programme should be placed on education, information and family planning.
Article
To investigate the effect of parity on Down syndrome (DS). The study was conducted on data from Northeast Italy (NEI) (1981-1996) and Sicily (ISMAC) (1991-1996) Congenital Malformation Registries. In these areas, all DS births are recorded and confirmed by chromosomal analysis; the NEI Registry also registers pregnancy terminations (TOPs) after prenatal diagnosis of DS. In order to estimate the effect of parity independently of the mother's age and to reduce the truncation effect, different age classes and three classes of parity (1, 2-4, >4) were defined. The study sample consisted of 1,088 consecutive newborns and 169 consecutive fetuses affected by DS. In both NEI and ISMAC samples, we found a significantly increased risk of having a DS child for multiparas > or =35 years of age. In the NEI sample, the inclusion of TOP data did not seem to modify this finding. In the ISMAC sample, a significantly reduced risk for primiparas was found at all ages. Our data confirm a higher risk of having a DS child in women with parity >4. As this effect is evident only in women > or =35 years age, its practical impact is null because these women are usually offered prenatal diagnosis in any case. However, the mechanisms involved, if this association is true, are very intriguing and the observation should stimulate scientific studies allowing a better knowledge of the nondisjunction mechanism.
Article
Few reliable data exist concerning the recurrence risk for individual trisomies or the risk for recurrence of trisomy for a different chromosome. We collected records from two sources: (1) prenatal diagnoses performed at the Hopital Sainte-Justine in Montreal and (2) karyotype analyses performed at Genzyme. Using the standardized morbidity ratio (SMR), we compared the observed number of trisomies at prenatal diagnosis with the expected numbers, given maternal age-specific rates (by single year). SMRs were calculated both for recurrence of the same trisomy (homotrisomy) and of a different trisomy (heterotrisomy). After all cases with an index trisomy 21 were combined, the SMR for homotrisomy was 2.4 (90% CI 1.6-3.4; P=.0005). For women with both the index trisomy and subsequent prenatal diagnosis at age <30 years, the SMR was 8.0; it was 2.1 for women with both pregnancies at age >/=30 years. For the other index viable trisomies (13, 18, XXX, and XXY) combined, the SMR for homotrisomy was 2.5 (90% CI 0.7-8.0). For heterotrisomy, the SMR after an index trisomy 21 was 2.3 (90% CI 1.5-3.8, P=.0007); the SMR did not vary with maternal age at the first trisomy. When all cases with index viable trisomies were combined, the SMR for heterotrisomy was 1.6 (90% CI 1.1-2.4; P=.04). For prenatal diagnoses following a nonviable trisomy diagnosed in a spontaneous abortion (from Genzyme data only), the SMR for a viable trisomy was 1.8 (90% CI 1.1-3.0; P=.04). The significantly increased risk for heterotrisomy supports the hypothesis that some women have a risk for nondisjunction higher than do others of the same age.
Article
Altered genetic recombination has been identified as the first molecular correlate of chromosome nondisjunction in both humans and model organisms. Little evidence has emerged to link maternal age--long recognized as the primary risk factor for nondisjunction--with altered recombination, although some studies have provided hints of such a relationship. To determine whether an association does exist, chromosome 21 recombination patterns were examined in 400 trisomy 21 cases of maternal meiosis I origin, grouped by maternal age. These recombination patterns were used to predict the chromosome 21 exchange patterns established during meiosis I. There was no statistically significant association between age and overall rate of exchange. The placement of meiotic exchange, however, differed significantly among the age groups. Susceptible patterns (pericentromeric and telomeric exchanges) accounted for 34% of all exchanges among the youngest class of women but only 10% of those among the oldest class. The pattern of exchanges among the oldest age group mimicked the pattern observed among normally disjoining chromosomes 21. These results suggest that the greatest risk factor for nondisjunction among younger women is the presence of a susceptible exchange pattern. We hypothesize that environmental and age-related insults accumulate in the ovary as a woman ages, leading to malsegregation of oocytes with stable exchange patterns. It is this risk, due to recombination-independent factors, that would be most influenced by increasing age, leading to the observed maternal age effect.
  • Kallan K