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Original Articles Indian Pediatrics 2003; 40:398-403 |
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Spectrum of Congenital Heart Defects Associated with Down syndrome in High Consanguineous Omani Population |
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P. Venugopalan, A. K. Agarwal* From the Department of Child Health, Sultan Qaboos University Hospital and *Department of Cardiology, Sultan Qaboos University Hospital, Muscat, Oman. Correspondence to: Dr. P. Venugopalan, Child Ward 2, Sultan Qaboos University Hospital, PO Box 38, PC 123, Muscat, Sultanate of Oman. Email: [email protected] Manuscript received: September 9, 2002, Initial
review completed: October 21, 2002, Objective: To identify the pattern of congenital heart defects (CHD) in children with Down Syndrome (DS) in an Omani population, and compare it with CHD in children without DS and with historical cohorts from populations with low prevalence of consanguinity. Setting: Open-access Paediatric Echocardiography Clinic at Sultan Qaboos University Hospital, Muscat, Oman. Design: Prospective study. Methods: All children with DS referred to the Clinic from 1995-1998 formed the subjects (Group I). Children without DS or other known associations of CHD seen at the clinic during the same period served as controls (Group II). Two-dimensional echo-Doppler studies were performed on both groups and the results compared. Results: CHD were detected in 54/90 (60%) children in Group I, compared to 698/2122 (32.9%) in Group II (P<0.001). The common CHD in Group I included secundum atrial septal defect (ASD; 18/54), atrioventricular septal defect (AVSD; 15/54) and ventricular septal defect (VSD; 14/54), and in Group II included ASD (175/698), VSD (175/698), patent ductus arteriosus (123/698), pulmonary stenosis (PS; 76/698) and AVSD (35/698). AVSD was more common (P <0.001) and PS less common (P = 0.03) in Group I. Aortic stenosis, coarctation of aorta, transposition of great arteries and complex heart diseases were not detected. Compared to several studies from populations with low prevalence of consanguineous marriages, our study showed a higher frequency of CHD in DS (P <0.05). Conclusions: A high frequency of CHD was documented in DS-children from a population with widely prevalent consanguinity. AVSD was most frequent in DS. An interesting observation was the relative rarity of some CHD in the DS population studied. Key words: Atrioventricular septal defect, Congenital heart disease, Down syndrome, Pulmonary stenosis.
Subjects and Methods Patients aged <13 years referred to the open-access Pediatric Echocardiography Clinic at Sultan Qaboos University Hospital, Oman over the 4-year period from 1995-98 formed the subjects for the study. DS patients were included irrespective of the presence or absence of any symptom, physical sign, ECG or chest X-ray abnormality to suggest CHD. Patients with chromosomal anomalies (other than DS), congenital rubella, and other known associations of CHD were excluded. The diagnosis of DS was confirmed by chromo-somal analysis of the peripheral blood lymphocytes. All patients with DS were placed in Group I, and those without DS or other diseases known to be associated with CHD in Group II. Group II patients were thus similar to Group I but without DS or other diseases associated with CHD. After detailed history and physical examination, each child had two-dimensional (2D) echocardiographic examination and Doppler studies using a Hewlett Packard 77020AC ultrasound scanner. Children below 3 years of age, except neonates in the first 4 weeks of life were sedated with chloral hydrate (50 mg/kg orally) given 30 minutes before the procedure; no sedation was used in older children or neonates. 2D-echocardio-graphic pictures were recorded in standard parasternal long axis, short axis, apical 4-chamber, subcostal and suprasternal views. Colour doppler, and pulse and continuous wave doppler were also performed on all patients. The presence and severity of any cardiac malformation was analyzed as per recom-mendations of the American Society of Echocardiography(4). Presence of atrioventri-cular septal defect (AVSD) was determined as either complete if a single common atrioventricular valve was present, or partial if both atrioventricular valves (mitral and tricuspid) were seen with primum atrial septal defect, inlet ventricular septal defect or cleft anterior leaflet of mitral valve. All cyanotic CHD except tetralogy of Fallot (TOF) and transposition of great arteries (TGA) were categorized as complex CHD, which included common arterial trunk, double outlet ventricles, double inlet ventricles, hypoplastic right ventricle, hypoplastic left ventricle, atrio-ventricular valve atresia and anomalous venous connections. The miscellaneous group included all acyanotic CHD that could not be categorized into one of the other groups. A similar approach had been followed in previous studies also(5-7). Persistent foramen ovale in the neonate and patent ductus arteriosus (PDA) in premature babies were not included in the analysis, however these were considered if they persisted beyond the first four weeks of life. Where multiple CHD were detected the patient was placed under the dominant defect. Additional anatomic defects were recorded separately and mentioned as such. The data were analyzed by SPSS software. Results A total of 2212 patients satisfied the entry criteria. Group I included 90 children aged 5 days to 12 years (mean ± SD = 2 ± 3 years; 7 <1 week, 12 <1 month), and included 52 males and 38 females (M : F = 1 : 0.7). CHD was discovered in 54 patients (60%) in this group. Group II included 2122 patients aged 1 day to 12.9 years (mean ± SD 2.7 ± 3.6 years, 78 <1 month), 1110 males and 1012 females (M : F = 1 : 0.9). Among these 2122 patients, only 698 (32.9%) had CHD. Comparison of two groups confirmed a higher frequency of CHD in Group I (P = 0.001). The major CHD in the two groups are shown in Table I. Out of the 15 patients with AVSD 6 had additional abnormalities; these included ASD in 1, PDA in 2 and VSD in 3. One patient with perimembranous VSD had in addition a secundum ASD. Comparison of the two groups for distribution of defects showed that Group I patients had a higher frequency of AVSD (P <0.001), whereas Group II had a higher frequency of PS (P = 0.03). Table I Congenital Heart Defects in Children with Down Syndrome (DS) (n = 54) and Those Without it (n = 698)
*Complete 10/54 and partial 5/54; + inlet defects not included. Discussion The frequency of CHD in DS patients in our study was compared with results from historical cohorts published in the literature (2,8-16), and the results are shown in Table II. Table II Comparison of Present* and Published Studies on Congenital Heart Defects (CHD) in Down Syndrome (DS)
*Present study; ASD = secundum atrial septal defect; AVSD = atrioventricular septal defect; NA = not applicable; NR = not reported; VSD = ventricular septal defect.
Cardiac malformations are common in DS, and published studies have reported frequencies ranging from 30 to 65% (Table II). Our hospital based prospective study has revealed 60% frequency of CHD in children with DS, which is higher than many studies (8,10,11,13-16), and also significantly higher than in our non-DS children. Since DS patients in this study were subjected to echocardiographic evaluation even in the absence of any symptom, physical sign, ECG or chest X-ray abnormality to suggest CHD, we believe this is a true representation of the frequency of CHD in children with DS in this population. The higher frequency of CHD in DS children observed in our study could just reflect the low number of patients in some of the published studies, as similar prevalence has been reported from larger studies like the one from California (2). Our finding of AVSD to be the commonest CHD in DS children is similar to many other studies (2,8-15), but a few have found VSD or ASD to be more common. However, none have compared their results with the CHD in children without DS. Our study clearly shows that although ASD and VSD were comparable in the two groups, AVSD emerged the most frequent defect in DS children. Another finding this report has brought to light is the lower frequency of PS and absence of certain CHD (AS, CoA, TGA and complex CHD) in DS children studied. It is possible that Trisomy 21 does not have any significant role in the pathogenesis of these anomalies. However many of these abnormalities are lethal in early life and might not have reached for the study. Only 7/90 patients in our study were evaluated within the first week of life. Furthermore, we did not perform fetal echo-cardiography or still-birth autopsy studies. However, Tennstedt et al.(17), who per-formed a necropsy study observed that AVSD, and VSD were common in chromosomally abnormal fetuses while TGA, PS, tricuspid atresia and single ventricle had normal karyotype more often. Similarly Grech and Gatt(18) and Freeman et al.(11) found only VSD, AVSD and ASD in his patients with DS. Larger studies have however shown evidence of these diseases, although less frequently in DS children(10,14). Consanguineous marriage is common in Arab countries, exceeding 50% in some communities(19). Comparison with published studies (Table II) showed that the 60% frequency of CHD in our DS patients is higher than reported from France (46.2%), Atlanta (44%), Australia (33%), Dallas (38%) and Chile (30%), which are all regions with low prevalence of consanguinity. A high frequency (65%) of CHD with DS has also been reported from Turkey, where consan-guinity is common(12). However, a similar population from Saudi Arabia revealed only 30% CHD with DS, but this was a small cohort with only 37 patients(13). It is difficult to explain the higher frequency noted in our study. An autosomal recessive gene involve-ment in CHD has been suggested by studies that have documented a higher proportion of first cousins in patients with CHD than in the general population(20). Study limitations Group II patients could be considered as not well defined, as it mainly depended on the referring physicians. Only 698 of the 2122 patients in this group were detected to have CHD. It could also be true that the group I and II are not strictly comparable, as echo-cardiography was performed in group I with or without suspicion of CHD, and in group II only in the presence of a clinical suspicion. Another approach would be to compare incidence of CHD in DS cases with that in all neonates, however only 12 patients in group I and 78 patients in group II were in the neonatal age group. We could not compare the prevalence of CHD in DS children of con-sanguineous parents and those of noncon-sanguineous parents, as relevant data were incomplete. Also, we could not compare the clinical manifestations, CHD and other malformations in DS children of consan-guineous parents with those of nonconsangui-neous parents. In conclusion, this hospital based prospective study of children with DS has revealed a relatively high frequency of CHD, the commonest being AVSD, and the frequency was higher than reported from populations with a low prevalence of consanguinity. PS was lower in frequency and AS, CoA, TGA and complex CHD were not identified in our DS children. Contributors: PV was responsible for study design, collection of data and write up of final manuscript. AKA reviewed the literature, helped in study design and writing of manuscript. Funding: None. Competing interests: None stated.
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