• Users Online: 162
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Contacts Login 

 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 36  |  Issue : 2  |  Page : 46-52

Cytogenetic study of down syndrome in Algeria: Report and review


1 Department of Ecology and Environment, Faculty of Natural Sciences and Life and Sciences of Earth and the Univers, Abou Bekr Belkaid University, Tlemcen 13000; Department of Medicine, Faculty of Medicine, Abdelhamid Ibn Badis University, Mostaganem 27000, Algeria
2 Department of Ecology and Environment, Faculty of Natural Sciences and Life and Sciences of Earth and the Univers, Abou Bekr Belkaid University, Tlemcen 13000, Algeria
3 Department of Environmental Sciences, Faculty of Natural Sciences and Life, Djillali Liabes University, Sidi Bel Abbes 22000, Algeria; Department of Biology and Geosciences, Université du Maine, Le Mans, France

Date of Submission08-Jan-2016
Date of Decision26-Jan-2016
Date of Acceptance02-Feb-2016
Date of Web Publication2-May-2016

Correspondence Address:
Fayza Belmokhtar
Department of Medicine, Faculty of Medicine, Abdelhamid Ibn Badis University, Mostaganem 27000
Algeria
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1011-4564.181526

Rights and Permissions
  Abstract 

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.

Keywords: Cytogenetic analysis, down syndrome, karyotype, maternal age, Algeria


How to cite this article:
Belmokhtar F, Belmokhtar R, Kerfouf A. Cytogenetic study of down syndrome in Algeria: Report and review. J Med Sci 2016;36:46-52

How to cite this URL:
Belmokhtar F, Belmokhtar R, Kerfouf A. Cytogenetic study of down syndrome in Algeria: Report and review. J Med Sci [serial online] 2016 [cited 2019 Sep 15];36:46-52. Available from: http://www.jmedscindmc.com/text.asp?2016/36/2/46/181526


  Introduction Top


Down syndrome (DS) is the most common autosomal abnormality and is the most genetic cause of mental retardation, appearing in about 1 of every 700 newborns.[1],[2] DS can be caused by three types of chromosomal abnormalities: Trisomy 21, translocation, or mosaicism.[2] Trisomy 21 is characterized by the presence of three copies of chromosomes 21, generally resulting from nondisjunction during maternal meiosis whereas the extra chromosome 21 in mosaic DS arises from mitotic nondisjunction in a chromosomally normal zygote.[3] For DS by translocation, the extra chromosome 21 translocated to other chromosomes or to the acrocentric chromosomes of D and G group that is, 13, 14, 15, 21, and 22.[4]

The cause of the nondisjunction error is not known, but there is a definite connection with maternal age. Advanced maternal age remains the major well-documented risk factor for maternal meiotic nondisjunction. The incidence of trisomy 21 conceptions increases with maternal age.[5] Subsequently, maternal parity was established as an additional independent risk factor [6] and genetic predisposition as third independent risk factor.[7],[8] An increase risk for DS may be the result of an autosomal recessive gene mutation, particularly in the Middle East where the rate of consanguinity is increasing.[9]

Karyotype analysis by chromosome banding remains the standard method to identify the cytogenetic variants of DS and to provide appropriate genetic counseling. Most cytogenetic studies in the world indicate that the most frequent type of chromosomal abnormalities in DS is free trisomy 21 with frequency ranges from 93% to 96%, mosaic DS presents a frequency between 2% and 3%, and translocation DS presents a frequency ranges from 2% to 5%.[10] However, these values show a geographical variation from the Eastern to the Western countries. In Algeria, the number of children with DS is about 80,000 cases.[11] No data is yet available about cytogenetic variants of DS in the Algerian population.

The aim of this study was to describe the cytogenetic profile of children with DS in the west region of Algeria, Tlemcen, study the impact of maternal age and other risk factors associated with this disorder, and then review and compare the findings of previous international studies with our results.


  Materials and Methods Top


Sample

The study was carried out on 42 children (22 with DS, 20 control subjects) aged 1–19 years old. They were recruited from the Pediatric Department of Maghnia Hospital and the psychomotor center for mentally challenged children of Maghnia during a period of 8 months (2013–2014). Information on age, birth order, parity parental age, parental consanguinity, and family history of DS at presentation were documented using a questionnaire. All tested individuals were voluntary donors which parents gave consent in compliance with ethical norms get by international conventions.

Karyotype analysis

Chromosome preparation was carried out from 2 to 5 ml of peripheral blood collected in sodium heparin in all cases with clinical features of DS. Chromosomal culture was done according to standard protocol.[12] Peripheral blood lymphocytes were stimulated for 72 h in incubator at 37°C with phytohemagglutinin-M (5 ng/l). Then, metaphases are harvested by adding colcemid (10 mg/l) for 120 min, followed by hypotonic KCl (0.075 M) treatment for 30 min, and fixation using stand 3:1 methanol-acetic acid. Finally, cells obtained were dropped on distinct slides.

The karyotype of each patient was determined by direct staining with Giemsa or by G-banding using banding trypsin solution and Giemsa for staining (GTG)[13] or by R-banding using phosphate buffer heated to 87°C, then Giemsa for staining (RTG).[14]

In each case, 25–50 metaphases were examined and 3–5 cells were photographed and karyotyped. In cases of mosaicism, 50–100 metaphases were scored. Karyotype description was done according to the ISCN (International Standard Committee on Human Cytogenetics Nomenclature).[15]

Statistical analysis

Data were analyzed using the software SPSS 17.0 for Windows (SPSS Inc., Chicago, IL, USA). Categorical variables were presented as the number and percentage, when the quantitative variables were presented as mean ± standard deviation. Student's t-test was used for comparison of means. P ≤ 0.05 was considered statistically significant.


  Results Top


A total of 42 children were included in this study. Twenty-two patients with DS, among them, 14 (63.3%) were males and 8 (36.4%) were females, with male to female ratio of 1.75:1. The mean age at referral was 11.2 years. About 81% of cases were of the last or second last birth orders. Parental consanguinity was reported in 22.7% of the cases. Only 1 patient has a similar case in his family [Table 1].
Table 1: Sociodemographic features of Down syndrome cases

Click here to view


Mean maternal age at first birth was significantly higher in (1990–2005) (27.2 ± 5.24 years) than in (1974–1989) (22.7 ± 3.92 years) (P = 0.016) in our studied population. The age at first parity increase in these last years [Table 1].

For the mean maternal age of mothers at birth of DS children was 36.27 ± 7.59 years (ranges 21–52 years), of which 54.5% were in the advanced age group (≥35 years). This mean was significantly higher than the maternal age of mothers of nontrisomic children, whose age was around 27.83 ± 6.34 years (P = 0.0002) [Figure 1].
Figure 1: Prevalence of normal and trisomic newborns according to maternal age at term

Click here to view


The chromosomal analysis were undertaken in 22 cases, out of which 20 (91%) cases had free trisomy 21, 1 case had trisomy 21 with translocation (46, XY, der (21;21)(q10;q10),+21), and 1 case had mosaic trisomy 21 (47, XY,+21/46, XY) [Table 2].
Table 2: Karyotype analysis of 22 Down syndrome cases

Click here to view


A comparison of the frequencies of trisomy 21, mosaicism, and translocation DS of the current study with results of previous international studies was carried out. The frequencies of different countries, including Algeria are summarized in [Table 3].
Table 3: Karyotype frequencies among studied Down syndrome cases and pooled data from worldwide surveys

Click here to view



  Discussion Top


Trisomy 21 is a common birth defect and can be diagnosed easily on the basis of clinical features. However, karyotyping is necessary for the confirmation of free trisomy 21, mosaicism, and translocation in DS children to determine the recurrent risk and to provide genetic counseling. The data reported in this study represent the first work of DS in Tlemcen, Algeria. All cases were diagnosed postnatally, where a karyotype analysis was done for all studied cases.

In this study, the overall sex ratio was 1.75:1. The excess of males to be universal and was reported in many studies in different countries. Our results are similar to those found by Kolgeci et al. in Kosovo (1.72:1),[42] and near to those of Amayreh et al. in Jordan (1.61:1).[28]

The higher male sex ratio may be the inherent tendency of Y belonging to the G group chromosome to be closer to its other members, 21 and 22, especially the smallest acrocentric the 21. The reasons for the excess of male DS-associated to the paternal errors are not yet clearly known.[47]

The birth order of children with DS 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 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. This increase the maternal age for the last births and consequence, the age at birth of DS children became higher in our results where 54.5% of births were over 35 years old.

The mean maternal age at birth of all studied DS children was 36.27 ± 7.59 years, this result agrees with the study of El-Gilany et al. in Egypt,[19] where the mean maternal age was 36.8 years, and the study of Jaouad et al. in Morocco;[5] the mean maternal age was 35.39 years. Also agrees with the result found by Verma et al. in Libya (35.62 years).[17]

Advanced maternal age remains the principal risk factor for trisomy 21. 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.[52]

For older mothers, the maternal age effect may be due to differential selection and accumulation of trisomy 21 oocytes in the ovarian reserve of older women.[53]

For younger mothers, the mechanism behind the nondisjunction is not well understood. One of the reasons could be that the ovaries of young women are biologically older than their chronological age, which may lead to increased incidence of nondisjunction.[54]

Parent's consanguinity was observed in 22.7% of the effected children with DS. This result agrees with those of literature, where about 17% of patients were products of consanguineous marriages in Egypt.[19] However, the effect of consanguinity on nondisjunction of chromosome 21 has not been clearly defined.[55],[56],[57]

In the current study, the frequency of nondisjunction (free trisomy 21), mosaicism, and translocation were 91%, 4.5%, and 4.5%, respectively. Our results are similar to a study performed in Tunisia by Chaabouni et al.,[16] where the frequencies were 91.2%, 4.8%, and 4%, respectively, and another study in India by Verma et al.[32] the frequencies were 91.6%, 4.1%, and 4.1%, respectively.

The frequency of nondisjunction in previous international studies in North Africa countries ranged from 91% to 96% [Table 3]. In Tunisia, we noted (91.2%),[16] Libya (96%),[17] Egypt (96.1%),[19] and Morocco (96.2%).[5] However, in Middle East, Asia, Australia, and America countries, the frequency ranged from 81% to 98%. The lowest frequencies were noted in Chile (81.9%),[45] India (83.8%),[34] Iraq (84.6%),[27] and Iran (88%).[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%).[43]

For mosaic DS, the frequency in previous studies varied from 0.6% to 18.1%. 0.6% was noted in Morocco [5] and Libya,[17] whereas 18.1% was noted in Chile.[45] Our frequency (4.5%) is similar to those found in Tunisia,[16] Malaysia,[31] and India.[4] However, it is higher than other reports in Egypt (0.8%),[19] Oman (2.79%),[22] Jordan (3.8%),[28] China (3.5%),[30] France (2.3%),[37] Danemark (2.6%),[39] and Brazil (3.1%).[43] In contrast, it is lower than that reported in Iraq (12.8%),[27] Iran (11.3%),[29] India (10.8%),[34] Bosnia (11%),[41] Mexico (8.4%),[44] and Chile (18.1%).[45]

Among all studied cases here and in previous studies, the frequency of translocation and mosaicism was very much lower than the frequency of free trisomy 21. This could be attributed to the high fertility rate and trends toward reproduction even at an advanced maternal age.[58]

For nondisjunction trisomy 21, the most common error is maternal nondisjunction in the first meiotic division, with meiosis I error occurring 3 times as frequently as meiosis II errors. Most mosaic cases result from a trisomic zygote with the mitotic loss of chromosome 21. The DS cases with unbalanced translocation usually are de novo and nearly 25% result from familial transmission.[31]

Various studies have reported the frequency of free trisomy 21 associated with structural and/or numerical anomalies of other chromosomes (nonclassical type of DS) to be 0.15%–2.4%. 0.15% was noted in Oman,[22] 0.67% in Libya, 17 0.7% in England and Wales,[38] 1.2% in Egypt,[58] and 2.4% in Turkey.[10] Whereas, in our study, we did not find this type of DS.


  Conclusion Top


In this study, cytogenetic analysis by karyotyping was done for all cases that have clinical features of DS to confirm the clinical diagnosis and to determine the frequency of different types of DS. Our results suggest that free trisomy 21 karyotype is more frequent in DS cases than translocation and mosaic karyotypes. These results were comparable to many international studies in the world. Of the various factors analyzed during the present study, advanced maternal age, and higher parity were the major influencing factors contributing to Down's syndrome. These should be considered as importan factors for genetic couseling and to make aware the affected families about the recurrence risk and the options available.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Mégarbané A, Ravel A, Mircher C, Sturtz F, Grattau Y, Rethoré MO, et al. The 50th anniversary of the discovery of trisomy 21: The past, present, and future of research and treatment of Down syndrome. Genet Med 2009;11:611-6.  Back to cited text no. 1
    
2.
Newberger DS. Down syndrome: Prenatal risk assessment and diagnosis. Am Fam Physician 2000;62:825-32, 837-8.  Back to cited text no. 2
    
3.
Kovaleva NV, Mutton DE. Epidemiology of double aneuploidies involving chromosome 21 and the sex chromosomes. Am J Med Genet A 2005;134A: 24-32.  Back to cited text no. 3
    
4.
Jayalakshamma, Margaret M, Amudha S, Tilak P, Devi R, Rajangam S. Cytogenetic analysis in Down syndrome. Int J Hum Genet 2010;10:95-9.  Back to cited text no. 4
    
5.
Jaouad IC, Cherkaoui Deqaqi S, Sbiti A, Natiq A, Elkerch F, Sefiani A. Cytogenetic and epidemiological profiles of Down syndrome in a Moroccan population: A report of 852 cases. Singapore Med J 2010;51:133-6.  Back to cited text no. 5
    
6.
Doria-Rose VP, Kim HS, Augustine ET, Edwards KL. Parity and the risk of Down's syndrome. Am J Epidemiol 2003;158:503-8.  Back to cited text no. 6
    
7.
Farag TI, Teebi AS. Possible evidence for genetic predisposition to nondisjunction in man. J Med Genet 1988;25:136-7.  Back to cited text no. 7
    
8.
Mokhtar MM, Abdel-Fattah M. Major birth defects among infants with Down syndrome in Alexandria, Egypt (1995-2000): Trends and risk factors. East Mediterr Health J 2001;7:441-51.  Back to cited text no. 8
    
9.
Zlotogora J, Shalev SA. The consequences of consanguinity on the rates of malformations and major medical conditions at birth and in early childhood in inbred populations. Am J Med Genet A 2010;152A:2023-8.  Back to cited text no. 9
    
10.
Demirhan O, Tanrıverdi N, Suleymanova D, Cetinel N. Cytogenetic profiles of 1213 children with Down syndrome in South Region of Turkey. J Mol Genet Med 2015;9:157.  Back to cited text no. 10
    
11.
Amoura M. 80.000 children with Down syndrome, in Algeria. Santé-Mag, N°4 March 2012, p16, (In French).  Back to cited text no. 11
    
12.
Ferguson-Smith MA. Techniques of human chromosome analysis. Ric Clin Lab 1974;4:297-335.  Back to cited text no. 12
    
13.
Seabright M. A rapid banding technique for human chromosomes. Lancet 1971;2:971-2.  Back to cited text no. 13
    
14.
Dutrillaux B, Lejeune J. A new technic of analysis of the human karyotype. C R Acad Sci Hebd Seances Acad Sci D 1971;272:2638-40.  Back to cited text no. 14
    
15.
Shaffer LG, McGowan-Jordan J, Schmid M, editors. ISCN. An International System for Human Cytogenetic Nomenclature. Basel: S Karger; 2013.  Back to cited text no. 15
    
16.
Chaabouni H, Smaoui N, Maazoul F, Ben Jemaa L, M'Rad R. Epidemiologic and genetic study of trisomy 21 in Tunisia. Tunis Med 1999;77:407-14.  Back to cited text no. 16
    
17.
Verma IC, Mathews AR, Faquih A, el-Zouki AA, Malik GR, Mohammed F. Cytogenetic analysis of Down syndrome in Libya. Indian J Pediatr 1990;57:245-8.  Back to cited text no. 17
    
18.
Ellaithi M, Nilsson T, Elagib AA, Fadl-Elmula I, Gisselsson D. A first cytogenetic study of Down syndrome in Sudan. J Dev Disabil 2008;14:54-60.  Back to cited text no. 18
    
19.
El-Gilany AH, Yahia S, Shoker M, El-Dahtory F. Cytogenetic and comorbidity profile of Down syndrome in Mansoura University Children's Hospital, Egypt. Indian J Hum Genet 2011;17:157-63.  Back to cited text no. 19
[PUBMED]  Medknow Journal  
20.
Qahatani MH, Faridi WA, Iqbal LM, Nazia N, Riaz A. Environmental, maternal and cytogenetic analysis of live born infants with Down's syndrome. J US China Med Sci 2011;8:143-9.  Back to cited text no. 20
    
21.
Al-Maweri SA, Tarakji B, Al-Sufyani GA, Al-Shamiri HM, Gazal G. Lip and oral lesions in children with Down syndrome. A controlled study. J Clin Exp Dent 2015;7:e284-8.  Back to cited text no. 21
    
22.
Al Harasi SM. Down Syndrome in Oman: Etiology, Prevalence and Potential Risk Factors. A Cytogenetic, Molecular Genetic and Epidemiological Study. Thesis from Freie Universität Berlin; 2010.  Back to cited text no. 22
    
23.
Murthy SK, Malhotra AK, Mani S, Shara ME, Al-Rowaished EE, Naveed S, et al. Incidence of Down syndrome in Dubai, UAE. Med Princ Pract 2007;16:25-8.  Back to cited text no. 23
    
24.
Wahab AA, Bener A, Sandridge AL, Hoffmann GF. The pattern of Down syndrome among children in Qatar: A population-based study. Birth Defects Res A Clin Mol Teratol 2006;76:609-12.  Back to cited text no. 24
    
25.
al-Arrayed SS. Review of the spectrum of genetic diseases in Bahrain. East Mediterr Health J 1999;5:1114-20.  Back to cited text no. 25
    
26.
Al-Awadi SA, Farag TI, Teebi AS, Naguib KK, El-Khalifa MY, Marafie MJ, et al. Cytogenetic profile of Down syndrome in Kuwait: A decade of experience. J Egypt Public Health Assoc 1991;16 (Suppl):259-69.  Back to cited text no. 26
    
27.
Al-Mefraji S. Is any relation between cytogenetic types of Down's syndrome and congenital heart disease. Iraqi J of Community Med 2012;4:304-7.  Back to cited text no. 27
    
28.
Amayreh W, Al Qa'qa' K, Al Hawamdeh A, Khashashneh I. Clinical and cytogenetic profile of Down syndrome at King Hussein Medical Centre. J R Med Ser 2012;19:14-8.  Back to cited text no. 28
    
29.
Mehdipour P, Saadat M, Noori-Daloii MR. Down's syndrome: Cytogenetic studies in 150 cases in Tehran. Med J Islam Rep Iran 1996;10:47-52.  Back to cited text no. 29
    
30.
Wang YF, Lin L, Chen ZY. Cytogenetic study of Down syndrome cases in Southern Hainan Province and report of a rare case of abnormal karyotype. Nan Fang Yi Ke Da Xue Xue Bao 2010;30:2592-3, 2595.  Back to cited text no. 30
    
31.
Azman BZ, Ankathil R, Siti Mariam I, Suhaida MA, Norhashimah M, Tarmizi AB, et al. Cytogenetic and clinical profile of Down syndrome in Northeast Malaysia. Singapore Med J 2007;48:550-4.  Back to cited text no. 31
    
32.
Verma IC, Mathew S, Elango R, Shukla A. Cytogenetic studies in Down syndrome. Indian Pediatr 1991;28:991-6.  Back to cited text no. 32
    
33.
Mandava S, Koppaka N, Bhatia V, Das BR. Cytogenetic analysis of 1572 cases of Down syndrome: A report of double aneuploidy and novel findings 47, XY, t(14;21)(q13;q22.3)mat, 21 and 45, XX, t(14;21) in an Indian population. Genet Test Mol Biomarkers 2010;14:499-504.  Back to cited text no. 33
    
34.
Chandra N, Cyril C, Lakshminarayana P, Nallasivam P, Ramesh A, Gonipath PM, et al. Cytogenetic evaluation of Down syndrome: A review of 1020 referral cases. Int J Hum Genet 2010;10:87-93.  Back to cited text no. 34
    
35.
Poddar G, De A, Adhikari A, Haldar A, Banerjee J, De M. Cytogenetic, socioeconomic status and biological study of Down syndrome patients. Int J Hum Genet 2012;12:173-8.  Back to cited text no. 35
    
36.
Ahmed I, Ghafoor T, Samore NA, Chattha MN. Down syndrome: Clinical and cytogenetic analysis. J Coll Physicians Surg Pak 2005;15:426-9.  Back to cited text no. 36
    
37.
Stoll C, Alembik Y, Dott B, Roth MP. Epidemiology of Down syndrome in 118,265 consecutive births. Am J Med Genet Suppl 1990;7:79-83.  Back to cited text no. 37
    
38.
Mutton D, Alberman E, Hook EB. Cytogenetic and epidemiological findings in Down syndrome, England and Wales 1989 to 1993. National Down Syndrome Cytogenetic Register and the Association of Clinical Cytogeneticists. J Med Genet 1996;33:387-94.  Back to cited text no. 38
    
39.
Zhu JL, Hasle H, Correa A, Schendel D, Friedman JM, Olsen J, et al. Survival among people with Down syndrome: A nationwide population-based study in Denmark. Genet Med 2013;15:64-9.  Back to cited text no. 39
    
40.
Devlin L, Morrison PJ. Accuracy of the clinical diagnosis of Down syndrome. Ulster Med J 2004;73:4-12.  Back to cited text no. 40
    
41.
Mačkić-Đurović M, Projić P, Ibrulj S, Čakar J, Marjanović D. A comparative analysis of the effectiveness of cytogenetic and molecular genetic methods in the detection of Down syndrome. Bosn J Basic Med Sci 2014;14:94-8.  Back to cited text no. 41
    
42.
Kolgeci S, Kolgeci J, Azemi M, Shala-Beqiraj R, Gashi Z, Sopjani M. Cytogenetic study in children with down syndrome among Kosova Albanian population between 2000 and 2010. Mater Sociomed 2013;25:131-5.  Back to cited text no. 42
    
43.
Trevisan P, Moraes FN, Mattos VF, Graziadio C, Rosa RF, Paskulin GA, et al. Cytogenetic profile of patients with Down syndrome in southern Brazil. Sao Paulo Med J 2014;132:253-4.  Back to cited text no. 43
    
44.
Garduño-Zarazúa LM, Giammatteo Alois L, Kofman-Epstein S, Cervantes Peredo AB. Prevalence of mosaicism for trisomy 21 and cytogenetic variant analysis in patients with clinical diagnosis of Down syndrome: A 24-year review (1986-2010) at the Servicio de Genética, Hospital General de México “Dr. Eduardo Liceaga”;. Bol Med Hosp Infant Mex 2013;70:29-34.  Back to cited text no. 44
    
45.
Astete C, Youlton R, Castillo S, Be C, Daher V. Clinical and cytogenetic analysis of 257 cases of Down's syndrome. Rev Chil Pediatr 1991;62:99-102.  Back to cited text no. 45
    
46.
Staples AJ, Sutherland GR, Haan EA, Clisby S. Epidemiology of Down syndrome in South Australia, 1960-89. Am J Hum Genet 1991;49:1014-24.  Back to cited text no. 46
    
47.
Petersen MB, Antonarakis SE, Hassold TJ, Freeman SB, Sherman SL, Avramopoulos D, et al. Paternal nondisjunction in trisomy 21: Excess of male patients. Hum Mol Genet 1993;2:1691-5.  Back to cited text no. 47
    
48.
Munsi AS, Hussain M, Rima R, Biswas R, Mahmud S, Sayeed A. Pattern of congenital heart diseases among clinically diagnosed Down's syndrome children. North Int Med Coll J 2014;6:18-20.  Back to cited text no. 48
    
49.
Chan A, McCaul KA, Keane RJ, Haan EA. Effect of parity, gravidity, previous miscarriage, and age on risk of Down's syndrome: Population based study. BMJ 1998;317:923-4.  Back to cited text no. 49
    
50.
Kava MP, Tullu MS, Muranjan MN, Girisha KM. Down syndrome: Clinical profile from India. Arch Med Res 2004;35:31-5.  Back to cited text no. 50
    
51.
Alp MN, Oral D, Budak T. Cytogenetic analysis of 584 cases with clinical diagnosis of Down syndrome. Dicle Tip Derg 2007;34:283-9.  Back to cited text no. 51
    
52.
Sheth F, Rao S, Desai M, Vin J, Sheth J. Cytogenetic analysis of Down syndrome in Gujarat. Indian Pediatr 2007;44:774-7.  Back to cited text no. 52
    
53.
Hultén MA, Patel SD, Tankimanova M, Westgren M, Papadogiannakis N, Jonsson AM, et al. On the origin of trisomy 21 Down syndrome. Mol Cytogenet 2008;1:21.  Back to cited text no. 53
    
54.
Schupf N, Kapell D, Lee JH, Ottman R, Mayeux R. Increased risk of Alzheimer's disease in mothers of adults with Down's syndrome. Lancet 1994;344:353-6.  Back to cited text no. 54
    
55.
Naguib KK, Al-Awadi SA, Moussa MA, Farag TI, Teebi AS. Effect of parental age, birth order and consanguinity on nondisjunction in the population of Kuwait. J Kuwait Med Assoc 1989;23:37-43.  Back to cited text no. 55
    
56.
Hamamy HA, al-Hakkak ZS, al-Taha S. Consanguinity and the genetic control of Down syndrome. Clin Genet 1990;37:24-9.  Back to cited text no. 56
    
57.
Hamamy H, Alwan A. Hereditary disorders in the Eastern Mediterranean Region. Bull World Health Organ 1994;72:145-54.  Back to cited text no. 57
    
58.
Mokhtar MM, Abd el-Aziz AM, Nazmy NA, Mahrous HS. Cytogenetic profile of Down syndrome in Alexandria, Egypt. East Mediterr Health J 2003;9:37-44.  Back to cited text no. 58
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Materials and Me...
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed2842    
    Printed25    
    Emailed0    
    PDF Downloaded147    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]