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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 11  |  Issue : 4  |  Page : 211-215

Study of congenital heart diseases among children with Down's syndrome


Department of Paediatrics, Sri Venkateswara Medical College, Tirupati, Andhra Pradesh, India

Date of Submission18-Mar-2022
Date of Decision02-May-2022
Date of Acceptance04-May-2022
Date of Web Publication27-Oct-2022

Correspondence Address:
Padmini Priya Banoth
Banoth, Assistant Professor, Department of Paediatrics, Sri Venkateswara Medical College, Tirupati 517 501, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcsr.jcsr_43_22

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  Abstract 


Background: Congenital heart disease (CHD) is the most common cause for morbidity and mortality among children with Down's syndrome.
Methods: This hospital-based descriptive study was conducted on 50 children with Down's syndrome aged <18 years presenting to the department of paediatric medicine at our tertiary care teaching hospital at Tirupati. The prevalence, pattern of congenital heart defects and various factors which are likely to influence the expression of CHD in Down's syndrome are reported.
Results: We observed CHD in 27/50 (54%) of patients studied. Ventricular septal defect (n = 40.7%) was s the most common, followed by endocardial cushion defects (n = 29.7%); atrial septal defect, patent ductus arteriosus and tetralogy of Fallot. CHD were more commonly seen in male children (58.6%); karyotyping showed translocation in 30/50 (60%) study subjects. Advanced maternal, paternal age, increased birth order and consanguinity showed a positive association with the occurrence of CHD in children with Down's syndrome.
Conclusions: Our observations suggest that routine screening of children with Down's syndrome for cardiac anomalies will help in early diagnosis and early institution of specific treatment.

Keywords: Congenital heart disease, Down's syndrome, Prevalence


How to cite this article:
Banoth PP, Badur M, Priyadarshini B, Cheni MA. Study of congenital heart diseases among children with Down's syndrome. J Clin Sci Res 2022;11:211-5

How to cite this URL:
Banoth PP, Badur M, Priyadarshini B, Cheni MA. Study of congenital heart diseases among children with Down's syndrome. J Clin Sci Res [serial online] 2022 [cited 2022 Dec 5];11:211-5. Available from: https://www.jcsr.co.in/text.asp?2022/11/4/211/350170




  Introduction Top


Down's syndrome, the most common form of mental retardation caused by a microscopically demonstrable chromosomal aberration, is characterised by well-defined and distinctive phenotypic features and natural history. It is caused by the triplication of all genes or a critical portion of chromosome 21. In 1866, John Langdon Down[1] wrote, Down's syndrome children have multiple malformations, but the most common is congenital heart diseases (CHDs),[2] which is followed by intellectual, physical growth, bone development and dental eruption. It is a common genetic disorder with an overall incidence of 1 in 800.[3] Nondisjunction is the most common form of the genetic condition. Trisomy 21 (95%), mosaicism and translocation (14,21), translocation (21,22) are other causes of Down's syndrome.[2],[4] The incidence of Down's syndrome[2] increases with increasing maternal age; hence, most physicians recommend that women who become pregnant above the age of 35 years or older undergo prenatal testing for Down's syndrome.[5] Increased incidence of about 50% compared with an incidence of 0.4% in infants with normal chromosomes[1],[6] Out of which, 30%–40% have complete atrioventricular septal defects (AVSD),[6],[7] which is followed by ventricular septal defects (VSD), atrial septal defect (ASD) (ostium secundum), patent ductus arteriosus (PDA) and tetralogy of Fallot.

The incidence of CHD among Down's syndrome cases varies from 30% to 65% in various previous studies, and the prevalence in our hospital can be calculated. The pattern of CHDs varies among geographic areas, and the pattern of CHD in our tertiary care centre can be highlighted. This study will elucidate various factors such as maternal age, consanguinity of parents, and order of birth, which are likely to influence the expression of CHD in Down's syndrome.


  Material and Methods Top


A descriptive study was conducted among Down's syndrome children of age <18 years over a period of year to study prevalence and pattern of CHD admitted to the Department of Paediatrics, Sri Venkateswara Ramnarain Ruia Government General Hospital, the tertiary care teaching hospital attached to Sri Venkateswara Medical College, Tirupati. Ethical committee clearance for the study was obtained from the Institutional Ethics committee, Sri Venkateswara Medical College, Tirupati.

Before collection of data, all subjects were briefed about the purpose of the study and written informed consent was obtained. All the tests and procedures were done free of cost and no financial burden was imposed on the patient. All suspected cases of Down's syndrome 18 years, fulfilling the clinical diagnostic criteria, were subjected to karyotyping. All karyotypically proven cases were included in the study.

After a detailed history and physical examination, the Down's syndrome cases were subjected to chest X-ray, electrocardiography and two-dimensional echocardiography with color Doppler by experienced cardiologist using Hewlett Packard Sonos 2000 phased array imaging system with 5.0 and 3.7 MHz transducers.

Statistical analysis

All the data entered in data collection form were entered into an excel spreadsheet, and data were analysed using the statistical software SPSS version 21 (IBM, USA). Qualitative data were analysed using the Chi-square test, and a P < 0.05 was considered statistically significant.


  Results Top


The distribution of study subjects by various factors and their presence with CHD is mentioned in [Table 1]. In the present study, out of 50 subjects with Down's syndrome, 27 (54%) had CHD. Gender distribution was similar (P=0.441) [Table 1].
Table 1: Association of various factors with presence of CHD in 50 patients Down's syndrome

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In the present study, 32% of the subjects were born out of 3rd degree consanguineous marriage of parents, and 10% were born out of 2nd degree consanguineous marriage of parents; 58% were out of nonconsanguineous marriage. A significantly higher proportion of subjects born out osf2nd degree consanguinous marriage had CHD (P=0.015) [Table 1].

In the present study, 20% of the subjects with maternal age ≤20, 33.3% of the subjects with maternal age between 21 and 25 years, 75% of the subjects with maternal age between 26 and 30 years, and 87.5% of the subjects with maternal age 31 years and above had CHD, and the difference was found to be statistically significant [Table 1].

In the present study, 38.2% of the subjects with paternal age between 21 and 30 years, 86.7% of the subjects with paternal age between 31 and 40 years, and 100% of the subjects with paternal age of 41 years and above had CHD, and the difference was found to be statistically significant [Table 1].

In the present study, 36% of the subjects were 1st birth order, 32% were 2nd order and 32% were the 3rd order of birth. In the present study, 33.3% of the subjects with 1st birth order had CHD, and 50% and 81.3% of subjects with 2nd and 3rd birth order respectively had CHD, and the difference was found to be statistically significant [Table 1].

In the present study, the genetic composition of 52% of the subjects was 47XY Trisomy 21, 34% was 47XX Trisomy 21, 6% was translocation, (14,21) 4% and 4% had translocation (21,22) and mosaicism, respectively. Among the subjects, 55.8% of the subjects with nondisjunction of chromosome, 33.3% of subjects with translocation (14,21) and 100% of subjects with translocation (14,22) had CHD, and the difference was found to be statistically not significant [Table 2].
Table 2: Patterns of genetic inheritance of Down's syndrome in study subjects

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In the present study, 20% of the subjects had a history of previous abortion, 50% of the subjects with a history of previous abortion and 53.1% of subjects without a history of previous abortion had CHD, and the difference was found to be statistically not significant [Table 1]. Among the subjects with a history of previous abortion, 40% of the subjects had VSD, 40% had endocardial cushion defect and 20% of the subjects had ASD.

Among 2% of the subjects who had a family history of Down's syndrome, 100% of the cases with a family history of Down's syndrome had CHD, and the difference was found to be statistically not significant.

VSD was the most common heart disease pattern seen in 40.7% of the cases, followed by endocardial cushion defect in 29.7% of the cases and ASD in 18.5% of the cases, PDA in 7.4% of the cases and tetralogy of Fallot in 3.7% of the cases. Out of the 8 cases of endocardial cushion defect, 6 cases had partial and 2 cases had complete endocardial cushion defect [Table 3].
Table 3: Distribution of CHD diseases (n=27)

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In the present study, 5 subjects had associated non-cardiac anomalies; 4 had hypothyroidism, 1 each had of the subjects had duodenal atresia, Hirschsprung's disease and leukaemia, respectively. Among the 5 cases with associated non-cardiac anomalies, 40% of the cases had VSD, 20% had PDA and 40% of the cases did not have any cardiac anomaly. Order of birth and maternal age are statistically significant risk factors for the expression of CHD in Down's syndrome [Table 4].
Table 4: Association of congenital heart disease and birth order, maternal age n Down's syndrome

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  Discussion Top


CHD is the common cause of long-term morbidity and mortality in Down's syndrome. Between 40%–50% of children with Down's syndrome have CHDs. Of these, 30%–40% have completed AVSD. Most of them can be managed successfully if the diagnosis is made early and the baby is referred for full corrective surgery before the irreversible pulmonary vascular disease is established.

The incidence of CHD in our present study is 54% which was similar the figures reported in a studies.[8],[9] conducted at All India Institute of Medical Sciences, New Delhi[8] and University of Alabama[9] (44% and 48%, respectively). Various published studies have reported results ranging from 30% to 65%.

The male:female ratio in the present study is 1:0.72, which similar to the figure reported in a study[10] in Oman. In the present study, 58.6% of male children with Down's syndrome had CHD, whereas only 47.6% of female children had CHD. However, this gender difference did not attain statistical significance.

In 86% of cases, the cause for Down's syndrome is a nondysjunction; 55.8% of them had CHD. A translocation (14,21) was found in 3 cases, and 1 of them had CHD. Translocation (21,22) was detected in 2 cases, and both had CHD. Two children were found to be mosaic, and no CHD was detected. Similar findings were reported in another study[11] from Karnataka. In this study,[11] carried out in 100 children with Down's syndrome 41/93 (44%) nondysjunction cases, 4/6 translocation cases had CHD. One case of mosaicism was studied, and this subject did not have CHD. Hence, a translocation carries more risk of being born with CHD, but it is statistically not significant.

As the order of birth of the child increases, the chances of being born with a CHD also increase. In the present study, about 81.3% of Down's syndrome born of the third order had CHD against 33.3% and 50% in the first order and second order, respectively. Similar findings were reported in another study[12] Where 32%, 51%, 71% of the first order, second order, third order born Down's syndrome children had CHD. This may be compounded by the maternal age, which increases as the order of birth increases.

Consanguinity increases the risk of heart defects in the general population. Likewise, when the Down's syndrome child is born of consanguineous marriage, it has more chances of being born with a CHD. In our study, all 5 cases with second-degree consanguinity had CHD. Seventy-five per cent of cases born of third-degree consanguinity had CHD. Among nonconsanguineous parentage, only 34.5% had CHD. Similar observatios were reported in another study.[10] Consanguineous marriage is common in Arab countries, exceeding 50% in some communities where incidence was 65% in Omani and 60% in Turkey populations.[10]

As the mother's age increases, the risk of giving birth to a Down's syndrome child also increases. Thirty-five years is taken as the cut-off, above which prenatal testing is mandatory. In the present study, 20% of Down's syndrome babies that were born to mothers ≤ 20 years of age had CHD. In the age group of 21–25 years, it is 33.3%, and in 26–30, it is 75%. The risk is more in the age group for more than 31 years, where 87.5% of babies born had CHD (P=0.037). Its P = 0.037, statistically significant. Similar observations were reported in another study.[12] where increasing maternal age increases the incidence of CHD. It shows in the maternal age group of 20–25 years, 26-30 years and 31 years and above the incidence of CHD among Down's syndrome children was 30.6%, 51% and 71.4% respectively.[12]

In our study, when the father was between 21 and 30 years, the incidence of heart defects was 38.2%, and in the 31–40 years of age group, it was 86.7%. In 1 case, the father's age was above 40 years, and the child had CHD. Its P = 0.018 which is statistically significant. This corresponds to report in another study.[12] where increasing paternal age increases the incidence of CHD. With incidence being 39.2% in the paternal age group of 21–30 years, The incidence of CHD in 31the paternal age group of 31-40 years and above 40 years was 55.9% and 100% respectively.

Ten mothers gave a history of previous abortions before the birth of the Down's child. Among them, 5 cases (50%) had CHD. ASD was detected in 1, VSD in 2, and endocardial cushion defect in 2 children. On one occasion, there was a previous Down's syndrome child in the family. CHD was found in that child. Hypothyroidism (4%) was detected in two cases. One child had Hirschsprung's disease (2.1%), one child had duodenal atresia (2.1%) and one child had acute lymphoblastic leukaemia (2.1%). Ninety per cent of the cases were free of associated non-cardiac abnormalities. A study reported gastrointestinal manifestations in 7.5% patients. Out of the 219 cases included in the study, congenital heart defects were reported in 47.5% of cases with 42.1% of them having complete AVSD.[13] Gastrointestinal tract malformations were present in 7.5% of cases and were frequently associated with a cardiac defect and a very high mortality rate. In a study[14] Among the most common non-cardiac anomalies reported in Down's syndrome were duodenal atresia (265-fold higher risk), Hirschsprung's disease (101-fold higher risk), and annular pancreas (430-fold higher risk). The paper lists 17 other anomalies more common with Down's syndrome than non-Down's syndrome.

In our study, VSD was the most common heart defect accounting for 40.7% of CHD, followed by endocardial cushion defect (29.7%). In a study[10] the common CHD in Down's syndrome children were ASD, secundum type (18/54), AVSD (15/54) and VSD (14/54) (P = 0.03).

As per other studies[14],[15],[16] the most common CHD in Down's syndrome was VSD followed by canal AVSD. A study[16] assessed the relationship between CHD and Down's syndrome in utero. In the group of 41 foetuses with known Down's syndrome, the incidence of CHD was 56% (AVSD 44%, VSD 48%, the remainder having other heart defects). Conversely, considering the incidence of Down's syndrome in foetuses with CHD, 43% of all AVSD (53% of AVSD with normal visceral situs) was associated with Down's syndrome, whereas none of the 39 cases of VSD was associated with Trisomy 21. They have confirmed that more than half of the foetuses with Down's syndrome bear a CHD, which is an AVSD in 44% of cases. Conversely, 43% of foetuses with an AVSD have Trisomy 21. For VSD, the situation is controversial due to the relatively low detection level of this heart defect at the routine mid-trimester obstetric scan. These studies are comparable with our study.

We had observed that occurrence of CHD was higher in children with Down's syndrome. Therefore, routine screening of these children for early diagnosis of cardiac abnormalities will be beneficial as early corrective surgery can be undertaken before irreversible pulmonary vascular disease is established. This study was conducted in a small sample from one geographical area, which cannot be generalised. Hence, more subjects from various geographical areas should be considered in future studies.

Acknowledgements

The authors would like to thank the Faculty of the Department of Paediatric Medicine, Sri Venkateswara Medical College, Tirupati, for their valuable suggestions during this work

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Calderón-Colmenero J, Flores A, Ramírez S, Patiño-Bahena E, Zabal C, García-Montes JA, et al. Surgical treatment results of congenital heart defects in children with Down's syndrome. Arch Cardiol Mex 2004;74:39-44.  Back to cited text no. 15
    
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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