Down Syndrome

Alternative Names

  • Trisomy 21
  • DCR
  • Down Syndrome Chromosome Region
  • DSCR
  • Down Syndrome Critical Region
  • Transient Myeloproliferative Disorder of Down Syndrome
  • Leukemia, Megakaryoblastic, of Down Syndrome
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Chromosomal abnormalities, not elsewhere classified

OMIM Number


Mode of Inheritance

Isolated cases

Gene Map Locus



Down syndrome (DS) is the most common genetic cause of mental retardation, affecting one in 700 live births. The phenotype of DS is complex and variable in severity, and includes mental retardation, cognitive deficits, heart defects, hypotonia, motor dysfunction, immune system deficiencies, an increased risk of leukemia and Alzheimer's disease.

DS is generally (95%) caused by the presence of three copies of chromosome 21. In about 5% of the cases, it results from translocation of an additional copy of chromosome 21 to another chromosome, tetrasomy of chromosome 21, or duplicated regions within chromosome 21. The region of chromosome 21 between the carbonyl reductase (CBR) and the ERG genes, which spans 2.5 Mb on 21q22.2, has been identified to cause partial trisomy 21 in DS patients. It contributes significantly to the pathogenesis of many characteristics of DS, including morphological features, hypotonia, and mental retardation. The DSCR3, DSCR4 and DSCR5 (Down syndrome critical region 3, 4, and 5) are found in this region. DSCR1 is located in 21q22.3, and is over-expressed in the brain of DS fetuses, leading to neurofibrillary tangles such as those associated with Alzheimer disease.

Molecular Genetics

Mutations in the GATA-binding protein 1 (GATA1) gene, located on Xp11.23, are associated with, megakaryoblastic leukemia with DS. The GATA1 protein plays an important role in erythroid development by regulating the switch of fetal hemoglobin to adult hemoglobin. On the other hand, polymorphisms in the [email protected] S-methyltransferase (MTR) gene, located on 1q43, are associated with increased risk for DS.

Epidemiology in the Arab World

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Other Reports


Al-Arrayed (1999) calculated the incidence of DS among Bahrainis to be 0.9/1000 according to data collected retrospectively from hospital records for the period 1989-1993. Of 104 Bahraini patients, cytogenetic analysis had been performed on 89 patients. The mean age of patients admitted was 5 years, with 60% of patients under 1 year of age; the oldest patient was 31 years old. The most common complications were chest infections, congenital heart disease, increased susceptibility to all types of infection, anemias, ear, nose and throat and eye complications. Karyotyping analysis showed that 97% of those studied had free trisomy, 2% had translocation, and one patient had a mosaic - a novel karyotype [47,XX,+21/47,-21,-22+r(22)] [9,10]. Later, Al-Arrayed (personal communication, Dubai, 2006) reported that the incidence rate of DS in years 1991-2000 in Bahrain was found to be 1.2/1000. The number of confirmed trisomy 21 cases during 2004 and 2005 among 15,000 newborns was 12 and 17, respectively; indicating a prevalence of 0.8/1000 and 1.1/1000, respectively.


Abdel Fattah et al. (1991) studied 371 cases with Mongoloid facies to detect the prevalence of acute leukemia among DS patients. The patients were subjected to case history, clinical examinations, intelligence quotient, CBC, X-ray, skeletal survey, ultrasonography, echocardiography, karyotyping and bone marrow examination. Of the 371 subjects, four patients (1.1%) showed acute lymphoblastic leukemia (ALL-LII), with symptoms of lymphadenopathy, and hepatosplenomegaly. The frequency of 1.1% indicated a high prevalence rate of acute leukemia among this group. The male:female ratio was 3:1 and the peak age incidence was in the 2-3 years age group. [Abdel Fattah S, Shawky RM, Kachef N. Acute leukemia in Down's syndrome. Egypt J Pediat. 1991; 8(1-2):181-5.]

Later, Abdel-Fattah et al. (1991) studied the same group of 371 patients (212 males, 160 females) and conducted full history taking, clinical examination, and investigations including IQ, radiological, ECG, eye, and fundus examination. Congenital anomalies were seen in 80.3% of the patients. The majority of the anomalies (43.7%) were related to the cardiac system, followed by ventricular septal defects (31.2%), defects involving the skeletal system (15.6%) and the genitounrinary system (5.4%). The most common characteristics seen in the patients were epicanthal folds (78.4%), transverse palmar crease (75.2%), brachydactyly (77.9%), and short fifth finger (70.9%). The prevalence of congenital anomalies was also significantly associated with the degree of parental consanguinity, and 90% of the consanguineous parents were first-cousins. Nine percent of the patients showed a positive family history for chromosomal anomalies. No statistical significance was found for the intake of teratogenic drugs and contraceptive pills by the mothers during the antenatal period. [Abdel-Fattah S, Shawky RM, Fattah SA, Kashef N. Congenital anomalies prevalent among Egyptian Mongols. Egyptian J Paediatr. 1991; 8(3-4):367-75.]

Shawky et al. (1993) evaluated the cell mediated immunity and its relation to the plasma zinc level in 20 DS patients (11 males and 9 females) and 10 normal individuals. There was a significant decrease in the plasma zinc level of the patients as compared to the control group. The WBC count was statistically comparable between the two groups. However, the T cell percentage was found to be significantly reduced in the patients. A significant decrease was also seen in the release of the migration inhibition factor by T lymphocytes in the DS group, although the response to the tuberculin test remained the same in both groups. A positive correlation was also found between the decrease in plasma zinc level of the patients, and decrease in their total T cell, and migration inhibition. Shawky et al. (1993) concluded that these patients had altered cell mediated immunity, partly due to zinc deficiency, and recommended that dietary zinc be supplemented to DS patients to improve their general health and resistance to infection. [Shawky RM, El-Shimi S, Abdel Alim K, El-Khashaab TH, Mahmoud A. Cell mediated immunity and zinc in children with Down's syndrome. Ain Shams Med J. 1993; 44(10-12):781-6.]

Later, Shawky et al. (1994) investigated the various abnormalities affecting the T cell subsets and NK cells in DS patients. The group consisted of 30 affected infants and children (16 males and 14 females) and 10 age- and sex-matched healthy children. The results revealed a significant decrease in the percentage of total T lymphocytes and T helper cells in the patients, indicating an impairment of cellular immune response. The patients also showed a significant increase in the T suppressor cells, and a reduced helper/suppressor ratio. The NK cell percentage was found to be significantly increased in the patients. Shawky et al. (1994) proposed that the complex impairment of cell mediated immunity and NK cell production was the basis of the defective immune response seen in DS patients. [Shawky R, El Shimi S, El Khashaab T. T-cell subsets and natural killer cells in children with Down's syndrome. Egyptian J Paediatr. 1994; 11(3-4):229-36.]

In 2000, Shawky et al. (2000a) studied the effect of early intervention programs on the cognitive development of DS children, by comparing a study group of 20 patients enrolled in the Portage program of early intervention, with a control group of 20 patients not attending any intervention programs. Shawky et al. (2000a) indicated that mothers in the study group were significantly better educated than those in the control group, with 80% of them having university degrees, compared to 20% in the control group. The Portage program showed a significant effect on the mental ages of the children. After initiating the Portage program, 40% of the children showed a mental age of 2-2.5, and 80% of them had mental ages appropriate to their chronological age, in comparison to only 5% in the control group. The average IQ of the children increased significantly (88) at the end of the program as compared to the beginning (56). [Shawky RM, El Sedfy HH, Aziz SS, Mohamed ARA. Early intervention and cognitive functions in Down syndrome. Egyptian J Med Hum Genet. 2000a; 1(1):123-34.]

In the same year, Shawky et al. (2000b) evaluated the use of PCR-based assays for the rapid and accurate diagnosis of DS. For this, 28 DS infants and children (18 males and 10 females; 1-month to 7-years of age) were compared to seven apparently normal children (3 males and 4 females; 7-months to 9-years of age). Oligonucleotide primers were synthesized to detect (GT)n polymorphisms at D21S120, D21S156 loci and the HMG14 gene, tetranucelotide repeat polymorphisms at the D21S11 locus, the S100B gene on chromosome 21, and a 165 bp fragment of the IGF1 gene on chromosome 12. None of the studied loci was exclusively identified all the 28 patients. The HMG 14-GT2 locus was the most informative, having been identified in 50% of the patients followed by the D21S11 locus which made possible the identification of 43% of the patients. Twelve different alleles were identified at this locus, the most frequent being allele No. 8 (0.355%). The D21S561 locus and the D21S120 loci identified 39% and 28% of the patients, respectively. The combined use of these markers identified 86% of the cases analyzed. [Shawky RM, Rifaat MM, El-Din MS, Khalifa OA. Rapid detection of trisomy 21 by quantitative PCR. Egyptian J Med Hum Genet. 2000b; 1(1):145-62.]

In a third study published the same year, Shawky et al. (2000c) assessed 17 DS patients (13 males and 4 females) for the pattern of regional cerebral blood flow (rCBF). Results showed developmental delay to be the most frequent manifestation (59%), followed by mongoloid facies (19%), and hypotonia (24%). A consanguinity rate of 35% was observed among the patients. The mean IQ of the patients was 45.2, and the IQ showed negative correlation with the age of the patient. Mental retardation ranged from mild (29%), to severe (24%), borderline (12%), and profound (6%). Mean mental age delay (MAD) was calculated at 6.11 years. Linguistic ability was the most impaired and deviant cognitive function in these patients, with a mean language age delay (LAD) of 3.6 years. Both the LAD and MAD were negatively correlated to the IQ. SPECT analysis revealed the presence of hypoperfusion in 83% of the cases. Cerebellar hyperfusion was found to be significantly correlated to development of hypotonia in the patients, attributable to a disruption of the cerebellar functions. Similarly, 36% of the patients with LAD > 24 months showed parietal hypoperfusion, indicating its importance in language development. Patients suffering from behavioral disorders showed frontal hypoperfusion. A significant positive correlation was seen between the IQ of the patients, and radiotracer uptake by their parietal lobe, reflecting upon the importance of the parietal lobe in the cognitive development. [Shawky RM, Zaky EA, Matta LF, El-Shoubary AM, Abdou IM. Assessment of the pattern of regional cerebral blood flow in Down syndrome using brain single photon emission computed tomography. Egyptian J Med Hum Genet. 2000c; 1(1):35-53.]

Later, Shawky et al. (2003) studied the effect of zinc sulfate 2% on the integrity of DNA in the process of apoptosis in 24 DS patients. Examination of the patients involved full history taking, karyotype and chromosome analysis, and DNA electrophoresis from peripheral blood samples before and after treatment with 2% zinc sulfate using 1% horizontal agarose gel electrophoresis and pulsed field gel electrophoresis (PFGE). Internucleosomal DNA fragments were detected by conventional gel electrophoresis in 50% of the cases. PFGE was able to resolve four of the five uncertain DNA patterns of conventional gel electrophoresis, and also identify two of the seven 'normal' samples as being apoptotic. The mean age for appearance of internucleosomal DNA fragments was 8.4 years (10.3 in males and 6.1 in females). However, the mean age for appearance of HMW DNA fragments associated with internucleosomal DNA fragments was lower in males (3.5 years) than in females (6.3 years). In 89% of the patients with apoptotic DNA, zinc therapy was able to restore normal DNA pattern. Shawky et al. (2003) noted that the mean age for the group with successful zinc therapy was significantly lower (5.3 years) than that in the unsuccessful group (16.5 years), indicating that age at start of therapy was an important factor. The successful therapy was also seen to be significantly associated with the type of apoptotic DNA; with the patients showing the presence of internucleosomal DNA fragments having a lower rate of success (82%), compared to the group showing presence of HMW DNA associated with internucleosomal DNA fragments (100%). [Shawky RM, Borai IH, Kamal TM, Mahmoud MMK. Detection of apoptosis in peripheral blood cells in Down syndrome patients before and after zinc therapy. Egyptian J Med Hum Genet. 2003; 4(2):49-60.]

Mokhtar et al. (2003) conducted a retrospective study that included 673 DS patients referred for genetic diagnosis between years 1992 and 2001 at the Department of Human Genetics in Alexandria. Karyotype analysis showed that the most common abnormality in the patients was the regular free trisomy 21 (95%), indicating advanced maternal age. There were 18 cases with Robertsonian translocation (2.7%), of which the most frequent were the t(14;21) described in eight cases. Of the latter, four cases with t(14;21) had sporadic mutations, whereas the rest were maternally inherited. There were six cases of t(21;21; four-sporadic and two-paternally inherited). Of the sporadic cases, one patient had an affected sibling. Mosaicism was seen in 0.7% of the cases. Non-classical mutations were observed in 1.2% of the cases; a higher frequency than previously reported. Regular trisomy was seen occurring along with pericentric inversion of chromosome 9 in three patients and with Robertsonian translocation [(13;14), maternally inherited, and (7;14), sporadic] in two other patients. Two cases had an extra supernumerary unidentifiable marker associated with chromosome 21. The overall sex ratio for the study was calculated to be 1.24. However, in the cases of the mosaics, it was 0.67. The mean maternal age for the regular trisomy patients was 38.2, while cases with translocation had low maternal age, supporting similar findings in previous reports.

Shawky et al. (2004) undertook a study to understand the activity of glutathione peroxidase enzyme (GPX) and the level of selenium as indicators of antioxidative metabolism in 40 DS patients (21 males and 19 females; mean age-3.95 years) and 10 normal controls (5 males and 5 females; mean age-3.95 years). The study revealed a significant increase in the mean GPX activity in the patients (609.43) as compared to that of the control group (504.20). Shawky et al. (2004) conjectured that this could be due to an adaptive response to the over-production of super oxide dismutase in the patients, as the SOD-1 gene is present on chromosome 21. The selenium levels showed no significant difference between the two groups. However, a significant association was seen between the selenium level and GPX activity in the patients, suggesting that selenium requirement of the enzyme was not met, and that there was a relative selenium deficiency. Later, Shawky et al. (2005) compared the prevalence of antithyroperoxidase antibodies in a group of 40 DS infants and children (26 males and 14 females) and 40 apparently healthy children (28 males and 12 females). This study indicated that subclinical hypothyroidism was the most frequently observed abnormality among the patients (32%) when compared to the control group (12%). The number of DS children who were positive for antithyroperoxidase (65%) was also significantly higher than that in the control group (15%). Shawky et al. (2005) recommended early administration of L-thyroxine in subclinical hypothyrodic patients affected by chronic autoimmune thyroiditis, to prevent complications. [Shawky RM, AbdelAziz EA, Elhossiny RM, Ahmed ME. Glutathione peroxidase enzyme and selenium level in patients with Down syndrome. Egyptian J Med Hum Genet. 2004; 5(1):103-9.]


Alfi et al. (1980) assessed various factors associated with Down syndrome (DS) to study the occurrence of a genetic control of nondisjunction in a highly inbred population in Kuwait where the rate of consanguineous marriages reached 40%. In their study, they reviewed the cases of 11,614 single births in Kuwait in the year 1970 and detected 20 cases of Down syndrome (1:581). All cases were of the trisomic type. Analysis of the results revealed increased maternal age and consanguinity to be significantly associated with a risk of having affected children. It was found that the relative risk for closely related parents was 4X greater than that for the unrelated parents. Alfi et al. (1980) suggested that trisomic Down syndrome was likely to be heterogeneous in its etiology, and that at least in a subgroup of these patients the non-disjunction may be genetically determined.

Al-Awadi et al. (1987) studied various intestinal malformations that were observed in the first 600 consecutive babies and infants with DS in Kuwait. It was found that 16 DS cases suffered from trisomy 21 while one patient with DS phenotype passed away before karyotyping, with the patient's mother being a balance translocation carrier (46XX,t(14q;21q)). The study demonstrated an incidence rate of 1.9/1000 for gut anomalies and 1.1/1000 for DS.

Farag and Teebi (1988) conducted a community genetic survey in two district hospitals in Kuwait (Jahra and Farwania Hospitals) demonstrating high prevalence of chromosomal aneuploidy, especially DS. Jahra Hospital provided medical care for an Arab population of 300,000, were Bedouins represented 80%. Amongst 6,874 consecutive live births at the hospital, 31 babies were found to suffer from autosomal trisomies and Bedouins or Kuwaitis with Bedouin ancestors represented 93.5%. In 29 cases, parental consanguinity was noticed with an average coefficient of inbreeding of 0.044. Within this group, two siblings, one suffering from trisomy 21 and the other from trisomy 18 had young first cousin parents. While in a different family two siblings were found to suffer from trisomy 21. Meanwhile, Farwania Hospital provided medical care for an Arab and non-Arab populations of 400,000, were Bedouins represented 15%. Amongst 8,045 consecutive births, 14 subjects were found to suffer from autosomal trisomies. Of those, Bedouins or Kuwaiti Bedouins represented 42.9%. Eight cases represented parental consanguinity with an average coefficient of inbreeding of 0.0225. From this data, Farag and Teebi (1988) found that the overall prevalence of DS was 2.5/1000 in the two districts, which was double the prevalence reported from Kuwait Maternity Hospital (1.1/1000). Farag and Teebi (1988) concluded that clusters of chromosome aneuploidy were observed in Bedouin families and that in Jahra district trisomy 13 and trisomy 18 are more common.

Al-Awadi et al. (1990) studied trisomy 21 in 635 DS patients in the Maternity Hospital in Kuwait. The patients consisted of 257 males and 278 females, with an age ranging between several hours to 40 years. They found trisomy 21 in 611 cases, translocation in 12 cases, mosaicism in 9 cases, and 3 cases had non-classical karyotypes. By comparing data from their study with global cytogenetic surveys, Al-Awadi et al. (1990) found that karyotypes in DS with regular trisomy 21, translocation, mosaicism, and non-classical karyotypes showed percentages of 92.9%, 4.3%, 2.2%, and 0.5%, respectively.

Murthy et al. (1990) quantitatively studied the frequency and types of acrocentric chromosome association in a DS child having the peculiar karyotype (46, XX, -14, -22, t dic (14p;22p), +21, 21S+) in the Maternity Hospital in Kuwait. The child inherited 21S+ from the mother and t dic (14p;22p) from the father; four siblings were all heterozygous carriers for this latter mutation. Murthy et al. (1990) suggested that acrocentric chromosome association is a heritable and a nonrandom event. They also suggested that subjects who are heterozygous carriers for translocations and variants are at higher risk of having a non-disjunction.

Al-Awadi et al. (1991) carried out a study on DS for the period between years 1979-1989 and confirmed the occurrence of 1024 (575 males and 449 females) subjects suffering from DS and experiencing various chromosomal abnormalities. The age of the affected subjects ranged between birth and 40 years. Different bonding methods were employed to determine chromosome abnormalities and revealed that trisomy 21 constituted 96.2% of the total cases while different translocations represented 2.3%. [Al-Awadi S, Farag T, Teebi A, Naguib K, El-Khalifa M, Marafie M, Bastaki L, Al-Othman S, Sundareshan T, Murthy D, Mohammed F, Abulhasan S, Redha A, Ramadan A. Cytogenetic profile of down syndrome in Kuwait: a decade of experience. The Journal of the Egyptian Public Health Association 1991; LXVI(Suppl. 1991):260-9.]

Naguib et al. (1992) studied seven unrelated families, employed in the petroleum industry, with each having two sibs suffering from DS to determine the occurrence of an autosomal recessive gene controlling non-disjunction in man. The male:female ratio was found to be 1.8:1 with mean maternal and paternal ages of 30.9+/- 1.862 and 37.5+/- 2.635 years, respectively. Paternal consanguinity was observed in two families, whereas maternal consanguinity was found in one family. Two families experienced one abortion and the examination of parental chromosome demonstrated normal results except for one with 16qh + (parental). Naguib et al. (1992) employed Dahlberg's equation and the complete ascertainment method, but did not possess enough evidence to eliminate the presence of an autosomal recessive gene controlling non-disjunction in man. [Naguib K, Al-Awadi S, Moussa M, Mohammed F. Down syndrome in sibs: a study of recessive hypothesis controlling nondisjunction. The bulletin of the High Institute of Public Health 1992; XXII (1):125-33.]

Malaviya et al. (1998) reported two Kuwaiti patients aged 28 and 30 years old, suffering from DS and who also developed acute gouty arthritis. The diagnosis of gout in both patients was confirmed through monosodium urate monohydrate (MSU) crystals in the synovial fluid of the affected joints. Malaviya et al. (1998) stated that comorbidity of Down syndrome and gout was not widely studied before due to the short life span of Down syndrome patients, but with the enhanced life expectancy of these cases, this type of association might occur more frequently. [Malaviya A, Abdella N, Mukhtar M. Down's syndrome with coexistent gout in 2 patients: is the association underreported or is the prevalence actually increasing? Med Principles Pract. 1998; 7:78-80.]

Al-Awadi et al. (1999) studied three unrelated families experiencing recurrent trisomy 21 in sibs in order to learn more about the increased recurrence risk in chosen families and the role of mosaicism in the cause of non-disjunction in man. The study included two Kuwaiti families (family I and III) and one non-Kuwaiti family (family II), with families I and II being consanguineous (less than second cousin, second cousin, respectively). A detailed chromosome analysis of the peripheral blood culture was performed for each DS subject and their parents. Low grade mosaicism was excluded using a minimum score of 100 cells per case. The diagnosis of trisomy 21 was verified in all three affected sibs in the three families. Al-Awadi et al. (1999) proposed the option of employing genetic predisposition to non-disjunction parental mosaicism in genetic counseling for families with sibs affected by trisomy 21. [Al-Awadi S, Naguib K, Bastaki L, Gouda S, Mohammed F, Abulhasan S, Al-Ateeqi W, Murthy D. Down's syndrome in Kuwait: recurrent familial trisomy 21 in sibs. Med Principles Pract 1999; 8:156-63.]

Ali et al. (2006) studied the cervical spine abnormalities associated with DS in 44 cases (29 males and 15 females) aged between 15-45 years. Clinical and radiographical assessment revealed that eight of the patients had asymptomatic atlantoaxial instability (AAI), five patients had congenital anomalies of C1-1, and 16 patients had cervical spondylosis. Ali et al. (2006) found that degenerative changes appeared earlier in DS patients than in normal populations. These changes increased with age and generally affected the lower cervical levels.


Mahfouz et al. (2001) conducted a retrospective analysis on 2010 cases of blood referred for constitutional karyotype analysis. Referrals were grouped into 16 different categories, of which reproductive failure represented the highest percentage (33%), followed by structural congenital abnormalities (14%), developmental delay (11%), DS (9.6%), and abnormal sexual development (8.2%), while other categories represented smaller percentages. The total rate of abnormality was 16%, and the highest abnormality rates were among the clinically-recognizable chromosomal syndromes, while lower percentages were detected among less specific referrals.

Mansour et al. (2005) conducted a retrospective study of 240 consecutive patients with congenital heart disease. The most common anatomic cardiac anomalies were ventricular or atrial septal defects (62), tetralogy of Fallot (39), pulmonary stenosis (25), and transposition of the great arteries (24). The heart lesions were divided physiologically into volume overload (90), cyanotic (87), and obstructive (63). In all, 105 syndromic subjects included the velocardiofacial syndrome (18), DS (17), CHARGE association (6), DiGeorge syndrome (5), Williams syndrome (3), Edwards syndrome (3), Noonan syndrome (3), VACTERL association (2), and Patau syndrome (trisomy 13) (2).

Abdullah and Abbas, 2010, studied a young Lebanese boy with Down syndrome and Elastosis Perforans Serpiginosa. 



Weber and Freeman (1999) reported a child with annular pancreas along with DS. The child had loss of the third and fourth part of the duodenum and of the proximal jejunum as well as an apple peel configuration of the remaining small bowel. The complete absence of branches from the superior mesenteric artery impaired the blood supply of the distal duodenum. Presence of the annular pancreas may have impaired the flow through the pancreaticoduodenal arcade, which would normally compensate for the distal vascular occlusion.

Venugopalan and Agrawal (2003) conducted a prospective study to identify the frequency of congenital heart disease (CHD) in Omani children with DS and compared it with that in a group of healthy children and studies reported from populations with low prevalence of consanguinity. The study group composed of patients less than 13 years old, who were referred to the pediatric echocardiography clinic during a four year period from 1995 to 1998. DS Patients, confirmed by chromosomal analysis, were included irrespective of the presence or absence of any clinical feature suggestive of CHD, with exclusion of those with other chromosomal abnormalities, congenital rubella, or with other associations of CHD. The group was divided into two subgroups; group I which was composed of patients with DS and group II which included all patients without DS or other diseases known to be associated with CHD. The CHD was classified into cyanotic (divided into tetralogy of Fallot, transposition of great arteries, or complex) and acyanotic heart disease (miscellaneous group included acyanotic diseases which could not be categorized) and if multiple lesions were detected in one patient, the patient would be classified under the dominant defect. Out of 2,212 patients included in the study, 90 (52 males and 38 females with a mean age of 2 years) had DS, while group II included 2,122 patients (1,110 males and 1,012 females with a mean age of 2.7 years) of whom 698 patients had CHD. Group I had a significantly higher frequency of CHD (60%) when compared to group II and those reported in other studies. Venugopalan and Agrawal (2003) believed that this frequency was a true representation of the frequency of CHD in children with DS in Oman since all patients with DS were included in the study irrespective of the presence or absence of CHD. The major defects in group I were secundum atrial septal defect (33% versus 25% in group II), atrioventricular septal defect (28% versus 5% in group II), and ventricular septal defect (26% versus 25% in group II), while other defects detected were patent ductus arteriosus, pulmonary stenosis and tetralogy of Fallot with frequencies of 9.3%, 1.9%, and 1.9%, respectively. Some congenital heart defects (aortic stenosis, coarctation of the aorta, transposition of the great arteries, and complex CHD) were not present in this group, but were seen in varying frequencies among group II. Statistically significant higher frequency of atrioventricular septal defect (p<0.001) was detected in DS patients (similar finding was present in other studies), while those without DS had significantly higher frequency of pulmonary stenosis (p= 0.03). Upon comparison with other studies, it was found that low frequencies of CHD among DS patients were detected among populations with low consanguinity, but higher frequencies were detected in populations where consanguinity was common.

Sawardekar (2005) conducted a study to establish the prevalence of major congenital malformations in children born during a 10-year period in an Omani hospital in Nizwa. Of the 21,988 total births in the hospital, 44 children were born with DS.

Jaiyesimi and Baichoo (2007) undertook a study to understand the patterns of congenital cardiac malformations in 110 Omani DS children (median age: 2 months). A high prevalence of cardiovascular malformations was detected in this population, with 57% of the patients showing at least one malformation. A total of 76 malformations were detected, the most common being atrioventricular septal defect (32%), atrial septal defects within the oval fossa (29%), patent ductus arteriosus (17%), and ventricular septal defect (14%).


In 2001, Al-Gazali et al. described a male child of a first-cousin couple of Palestinian origin who had DS and neural tube defect. The child also presented cervical meningomyelocele, agenesis of corpus callosum, hydrocephaly, cerebellar herniation into the foramen magnum, and shallow posterior cranial fossa. He had a five-fold increase in cystathionine level relative to normal children, consistent with over-expression of the cystathionine beta synthase gene present on chromosome 21. Al-Gazali et al. (2001) suggested that altered folate status plus homozygous mutation in the MTHFR gene in the mother could promote chromosomal instability and meiotic non-disjunction resulting in trisomy 21.

Merrick (2001) provided an overview of DS-related statistics among Arab populations. The number of antenatally diagnosed DS cases in 1997 among Arabs was 70, of which 25 were terminated. In the same year there were 38,338 births among Arab women with 45 live births with DS. It is worth mentioning that the percentage of cases in which DS is detected and terminated during pregnancy was 36% among the Arab population group.


While studying patients born with double-chambered right ventricle defects, Eltohami et al. (1994) found two Qatari patients with DS among 10 cases with the cardiac condition. This high percentage of patients with this comorbid condition hinted to the possibility of a hitherto unrecognized association between the two. Percentages of both DS affected individuals in the population and the co-association of the two conditions were found to be similar between hospital settings in Qatar and the USA. In addition, 33% of DS patients in Qatar were found to also be affected with atrioventricular cushion malformation.

Abdul Wahab et al. (1998) reviewed 35 cases (17 Qatari nationals) of bronchiectasis diagnosed in Qatar during a 12-year period. One of these patients was recognized as probably having DS with A-V canal as the underlying factor leading to brochiectasis. [Abdul Wahab A, Al-Araby I, Dawod ST. Bronchiectasis in childhood in the state of Qatar. Qatar Med J. 1998; 7(2):8-13.]

Wahab et al. (2006a) studied the incidence pattern of DS in Qatar over a period of 5-years (2000-2004). Of the 30,076 Qatari babies born in the country in this period, 65 DS cases were diagnosed, giving an incidence of 1:546 live births. Wahab et al. (2006a) explained this high incidence to be due to the tendency towards increased maternal age. In this study, the mean maternal age was 35.4 years, while the mean paternal age was 40 years. Chromosomal analysis of the cases revealed regular trisomy to be the most common abnormality detected (98%). Wahab et al. (2006a) was of the opinion that a virtual absence of antenatal screening measures and the lack of prenatal diagnosis and termination of pregnancy were other factors for the increased incidence of DS in this population.

In the same year, Wahab et al. (2006b) retrospectively studied the medical records of all DS patients diagnosed in three hospitals in Qatar between 2000 to 2005. A total of 146 cases of DS below 5 years of age were diagnosed out of a total of 74,980 births, giving the condition a prevalence of 19.5/10,000 live births in Qatar. Of these cases, 40.4% were Qataris. Among the Qatari patients, males had a significantly lower incidence of DS (32%) compared to females (49%). Majority of patients diagnosed were infants, with a mean maternal age was 35.4 years. About 48% of patients had congenital heart conditions. Karyoptype analysis indicated that the most common anomaly was trisomy 21 (98%). Other abnormalities found included mosaicism and non-classical karyotypes, such as 47 XY t(Y;9)(p10:q10) + 21. In addition, a little more than half of the children had congenital heart problems. Wahab et al. (2006b) noted a significant positive association between DS and increased maternal age.

Saudi Arabia

A study by Niazi et al. (1995) determined the incidence of DS in Riyadh to be 1 in 554 live births. The study scanned 23,261 consecutive live births to Saudi women over a period of nine years (1982-1991) to find 23 females and 19 males suffering from DS. In the vast majority of these patients, the cause was non-disjunction trisomy 21.

Al Harbi (2003) reported the first case recorded in the literature of a girl born to a diabetic mother who had a comorbidity of DS and prune-belly anomalies (bilateral gross hydronephrosis, megaureter, and megacystis with abdominal muscle deficiency). The girl also had an atrioventricular septal defect. Diagnoses were confirmed with a cytogenetic study and micturating cystourethrography. She died at 29 days of age with a sudden collapse, most likely due to sepsis.

United Arab Emirates

El-Kalla and Mathews (1990) analyzed 1,630 cultures by chromosomal analysis.  In the pediatric age group (56% of the cases), 11.2% were found to be affected with a gross chromosomal aberration.  The largest group (6.4%) of chromosomal aberrations was that of trisomy 21 (average incidence of 1/500 birth).  El-Kalla and Mathews pointed that the problem of DS in Dubai is an enormous one.

In 1994, Quaife and Al Gazali described a consanguineous national family in which three living siblings (two males and one female) had free trisomy 21.  The family had seven other children who were all normal.  The parents were first cousins and had a history of two miscarriages.  The paternal grandfather married three times and had a total of six miscarriages and two neonatal deaths from the first two wives.  The great grandparents were also first cousins.  The father had obvious and large satellite regions on one of his 21 chromosomes. [Quaife R, Al Gazali L. A case of consanguineous parents with three living trisomy 21 children. Emirates Med J. 1994; 12:150-3.]

Topley et al (1995) identified three infants with choanal atresia and one infant with choanal stenosis who were born during a 5-month period at Tawam Hospital in Al Ain.  This apparent cluster of cases prompted a review of previous cases in the hospital, thus, bringing the total number of cases analyzed to eight.  Interestingly, all had at least one other congenital anomaly.  Identifiable syndromes included Down syndrome in one case.  Topley et al. (1995) suggested that choanal atresia and the associated anomalies were thought to be the consequences of the interference with the migration of neural crest cells, and the influence of chemical and genetic factors.

Al Talabani et al. (1998) studied the pattern of major congenital malformations in 24,233 consecutive live and stillbirth in Corniche Hospital, which is the only maternity hospital in Abu Dhabi, for the period between January 1992 to January 1995.  A total of 401 babies (16.6/1,000), including 289 Arabs, had a major defect.  Chromosomal anomalies accounted for 19% of the cases.  In their study, Al Talabani et al. (1998) observed 50 cases of DS (trisomy 21) in Arab families from the United Arab Emirates; including two cases of trans 21,21.  Recurrence was not reported in other members of the families.  Al Talabani et al. (1998) concluded that this study is very close to representing the true incidence of congenital abnormalities in the whole United Arab Emirates, as it included over 98% of deliveries in Abu Dhabi, the capital of United Arab Emirates, for that period.

Hosani and Czeizel (2000) evaluated the pilot dataset [March-May 1998] of the UAE National Congenital Abnormality Registry (NCAR).  A total of 4,861 births were recorded in this study period, with a birth prevalence of total congenital anomalies being 30.3/1,000 births.  Down syndrome was identified in 11 neonates, resulting in an incidence rate of 2.26/1,000 births.

In the same year, Nawaz et al. (2000) described 52 children with different types of congenital diaphragmatic hernia, where five had Morgagni’s hernia.  One child also presented features of DS.

Gururaj et al. (2002) reported a 3-year-old Arab child who was admitted with repeated episodes of strokes and demonstrated a comborbidity of moyamoya syndrome and DS (47XY+21).  Investigations showed that his protein C level was significantly low (47%).  Magnetic resonance angiography (MRA) showed normal internal carotid arteries on both sides up to the level of bifurcation.  Beyond that a meshwork of collateral vessels was seen.  Gururaj et al. (2002) raised the possibility of a link between protein C deficiency and DS with moyamoya syndrome.

Murthy et al. (2007) performed a study to describe the incidence of DS in Dubai by examining 24,250 newborn UAE nationals during a 5-year period.  The mean maternal age was 33.48 years and about 42% of the mothers were above 35 years old.  Cytogenetic studies identified trisomy 21 in most DS cases, and a maximum of two patients had a translocation or a mosaic.  Murthy et al. (2007) calculated the overall incidence of DS to be 1 in 449 live births among Emiratis and 1 in 602 live births among non-Emiratis in the Emirate of Dubai.  In having a higher incidence of DS, Emiratis in Dubai were no exception to the trend prevailing among Arabs from neighboring countries.  Such a trend is thought to result from advanced maternal age and high parity.

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