Profile of clinical features, congenital heart disease and other comorbidities in children with Down syndrome in a tertiary care centre in Nigeria

Background: Down syndrome (DS) is a common chromosomal disorder associated with congenital heart disease (CHD) which could lead to severe morbidity or mortality. Objective: To determine the frequency and spectrum of clinical features, CHD and other comorbidities in children with DS in a tertiary care centre in Nigeria. Method: Consecutive children with clinical features of DS were recruited. The frequency of clinical features and co-morbidities were noted. All the children had echocardiographic evaluation to identify those with CHD. Results: A total of 64 children was recruited of which 36 (56%) were male. Fifty one (80%) had CHD of which atrio-ventricular septal defect (AVSD) was the commonest, being found in 20 (39%) children. Common clinical features present were oblique eyes in 64 (100%), depressed nasal bridge in 60 (94%) low set ears in 53 (83%) and epicanthal folds in 50 (78%). Conclusions: Prevalence of CHD amongst DS children in this study was 80% with AVSD being the commonest. The most prevalent clinical features seen in these children were oblique eyes, epicanthal fold, depressed nasal bridge, low set ears, hypertelorism and hypotonia. DOI: http://dx.doi.org/10.4038/sljch.v47i1.8430 (


Introduction
Down syndrome (DS) is the commonest chromosomal disorder 1 .In a large Nigerian _________________________________________ 1 University of Benin Teaching Hospital, Nigeria *Correspondence: ehidiamen.sadoh@uniben.edu(Received on 09 May 2017: Accepted after revision on 16 June 2017) The authors declare that there are no conflicts of interest Personal funding was used for the project.Open Access Article published under the Creative Commons Attribution CC-BY License hospital, the incidence was reported to be 1 in 87 live births 2 .The incidence is associated with advanced maternal age 3 .DS is a significant cause of mental retardation in children and is associated with other morbidities such as leukaemia, Hirschsprung disease and cardiovascular anomalies 1,4,5 .The most severe comorbidities are the cardiovascular anomalies and when untreated, they are often the cause of death in affected children 6 .
A variety of congenital heart disease (CHD) has been described in patients with DS.Atrioventricular canal defect (AVSD) has been reported to be the commonest CHD seen in children with DS 1,7 while others have reported a preponderance of ventricular septal defect 8 .Otaigbe et al 9 in Port Harcourt, Nigeria evaluated 31 children with DS, all of whom had CHD which included a fairly wide spectrum of both acyanotic and cyanotic CHD.The most common CHD was patent ductus arteriosus (PDA), contrary to the report of the study done by Onalo and co-worker 10 in Abuja Nigeria where AVSD was the predominant CHD found amongst 20 children with DS studied.However, the sample sizes of the earlier Nigerian studies were rather small 7,9,10 .
There are typical dysmorphic features seen in DS patients that aid its clinical diagnosis 1 .The prevalence of these features varies from setting to setting as reported by various workers 1,11,12 .The differences may be due to the genetic variability.DS has high genotype variability and three types have been described viz.non-disjunction, unbalanced translocation and mosaicism 1 .

Objectives
The present study was conducted to determine the frequency and spectrum of clinical features, CHD and other comorbidities in children with DS seen at the University of Benin Teaching Hospital, Benin City, Nigeria, a tertiary care centre.

Method
All children clinically diagnosed to have DS who presented in the children's emergency room, paediatric wards and consultant out-patient clinics were referred to the echocardiographic laboratory of the University of Benin Teaching Hospital (UBTH), Benin City, Nigeria.It is the hospital policy to refer all suspected cases of DS for cardiologic evaluation.The study was carried out between July 2012 and December 2013.Ethical approval for the study was obtained from the research and ethics committee of the UBTH.
Using a pre-tested proforma, socio-demographic parameters of the children and parents and the clinical features of the children were obtained including age, gender, socioeconomic class (SEC), maternal and paternal ages.Each child then had a thorough clinical examination.Using a checklist, the clinical features associated with DS were noted.Other clinical signs of cardiovascular origin such as cyanosis, respiratory distress, chest wall abnormalities and cardiomegaly (displaced apex beat) were looked out for and documented.The presence of the co-morbidities of pneumonia, congestive cardiac failure (CCF) and pneumonia complicated with CCF, for which the patients were referred for cardiologic evaluation, were also noted.The diagnosis of pneumonia was based on clinical findings and typical pulmonary infiltrates seen on chest radiograph.The diagnosis of heart failure was based on the clinical diagnostic tool by Omokhodion 13 .The SEC was determined using the methods described by Olusanya et al 14 .The patients' weights were measured using a bassinet weighing scale for infants and an appropriate weighing scale for older children, using standard methods.The Z scores of the weight for age were computed using the WHO growth charts for children 15 .
All the children with a clinical diagnosis of DS underwent transthoracic echocardiographic evaluation using 2D, M mode and Doppler interrogation using an Aloka Prosound SSD-4000SV (Aloka, Meerbusch, Germany) machine.The analysis of the reports was done according to the recommendations of the American Society of echocardiography 16 .The presence and types of CHD on echocardiography were documented.

Statistical analysis
The data was entered into SPSS version 16 (Chicago IL) spread sheet and analysis done with the same tool.Simple proportions were expressed in percentages.Differences in proportions were tested with X 2 test.Level of significance was set at p <0.05 level.

Results
Of the 64 children with DS, 36 (56.2%) were male.The median age was 6 months with a range of 2 days to 15 years.The socio-demographic characteristics and parental age groups of the study population are shown in table I.A total of seven (10.9%) deaths were recorded.Two of the deaths occurred at home after discharge from the hospital and five occurred in the hospital during the study period.The deaths were related to severe respiratory problems and the underlying congenital heart defects.Sixteen (25%) of the 64 children with DS were lost to follow up while 38 (59.4%) are being followed up in the clinic.

Discussion
The prevalence of cardiac anomalies of 79.7% in this study is similar to the 77.1% recorded by Asani et al 7 in Kano, Nigeria but lower than the 100% recoded by Otaigbe et al 9 in Port Harcourt, Nigeria.The higher value recorded in the Port Harcourt study has been attributed to the fact that referral for echocardiography was based on the suspicion of possible cardiac defect while in the present study, all the children seen with DS were referred for echocardiographic evaluation irrespective of whether cardiac anomaly was suspected or not.The prevalence in our study is however higher than the 40 to 60% reported incidence studies globally [17][18][19] .
The majority of the children with DS in this study were underweight.This may be due to the fact that the prevalence of CHD was high in this study and the majority of the CHD were shunt lesions that could lead to recurrent pneumonia and heart failure.These co-morbidities would contribute to the underweight seen in these children.The finding of high prevalence of underweight children with DS is in tandem with the Brazilian study that showed that 78.2% of study subjects were underweight 11 .
The commonest CHD in this study was AVSD which is consistent with the Kano 7 and Abuja 10 studies in Nigeria and other previous works outside the country 6,20 .This is however at variance with the Port Harcourt 9 study which recorded patent ductus arteriosus (PDA) as the commonest and a study in Riyadh, Saudi Arabia 8 which recorded VSD as the commonest.It is not clear why there is a varied pattern in the distribution of CHD in different localities; it is possible that the genetic heterogeneity of the condition may be contributive.
The spectrum of CHD included complex congenital heart disease such as single ventricle and PTA.The presence of complex congenital heart defect was similarly reported in the Port Harcourt 9 study where they found double outlet right ventricle.This finding of complex congenital heart diseases has been reported in other previous studies outside the country 8,21 .Most (80.4%) of the CHD recorded in this study were isolated lesions which is consistent with the Kano study and other studies outside the country 7,8,22 .In the Port Harcourt study 9 , however, the majority (71%) of the patients with DS had multiple cardiac defects.It is not clear what is responsible for this finding.It is possible that it could be environmental; the higher prevalence of CHD in the oil rich Niger-Delta region of Nigeria has been alluded to in an earlier study 23 .
Two thirds of the patients with DS in this study were born to mothers younger than 35 years.This is consistent with previous studies that have shown a higher prevalence of DS born to younger mothers 4,9 .The occurrence of a growing number of children with DS born to younger mothers presents a strong reason for advocating DS screening for pregnant mothers as is done in some other countries 24,25 .Two factors may militate against a successful screening programme in the country.It is expensive and may be beyond the reach of majority of Nigerians; however the cumulative cost of caring for a DS child certainly outweighs the cost of screening 26 .The other factor is managing the outcome of a positive screening result.Nigerian couples may be unlikely to accept termination of pregnancies because of their religious beliefs.
This study demonstrated that the clinical features present in patients with DS in the study locality in at least 70% of cases are oblique eyes, depressed nasal bridge, low set ears, epicanthal folds, hypertelorism and hypotonia.There is variation in the frequency of clinical features from locality to locality.For instance, single simian crease was present in 23.4% of the patients in this study; this is lower than the 39% recorded in the Port Harcourt study 9 and the 83.9% in the Brazilian study 11 .There were no Brushfield spots identified in this study, which is similar to a Korean study 27 , but at variance with a Jordanian study 28 where 9% of children with DS had Brushfield spots.The difference in findings may be due to the known low frequency of Brushfield spots in DS individuals with dark coloured irides 29 .
Although in older infants and children, the features of DS are easily identifiable and thus a clinical diagnosis is made with a high level of certainty, in some others especially newborns, clinical diagnosis is less clear.The limitation of this study is the absence of cytogenetic studies to confirm DS in the suspected children.This was because the facility was not available.

Conclusions
 Prevalence of CHD amongst clinically diagnosed DS children in this study was 80% with AVSD being the commonest.
 The most prevalent clinical features seen in children with DS in this study were oblique eyes, epicanthal folds, depressed nasal bridge, low set ears, hypertelorism and hypotonia.