Sir,

In recent issues of your journal, we read the interesting papers by Samson and Kumar¹, and by Vida et al.² These studies although concerning different topics, provide interesting data regarding the prevalence of congenital cardiac malformations in patients with Down's syndrome. Samson and Kumar¹ reported that, in their neonatal population with Down's syndrome from Arab Emirates, “ventricular septal defects and atrial septal defects in the oval fossa are the most common malformations”. In contrast, Vida et al.² reported that the most frequent malformation in patients with Down's syndrome in Guatemala is patency of the arterial duct, albeit followed by ventricular septal defect.

These findings are in contrast with the classic epidemiological papers on cardiac disease in patients with Down's syndrome, which show atrioventricular septal defect with common atrioventricular junctions to be the most common congenital cardiac malformation in Caucasian populations.³

It is of interest to note, therefore, that also in Chinese⁴ and Japanese^{5, 6} populations, the most frequent cardiac malformation in patients with Down's syndrome is not an atrioventricular septal defect with common junction, but a ventricular septal defect. Mexican data⁷ is similar to the oriental findings, because the most common cardiac defect is again ventricular septal defect, followed by atrioventricular septal defect. It would be of interest, of course, to know whether any of those reported with ventricular septal defect also had common atrioventricular junctions.

A definitive explanation for this different prevalence of congenital cardiac malformations in children with Down's syndrome, however, remains unknown.

There are several hypotheses. The authors from Arabian countries suggest the possible role of the time of the screening. The high number of ventricular septal defects found in their study could be due to the neonatal age of their patients, since some ventricular and atrial communications could close spontaneously with time. Another explanation for the prevalence of patency of the arterial duct in patients with Down's syndrome from Mexico, Perù and Colombia, as proposed by Vida et al.,² is the lower partial pressure of oxygen at high altitude. Other reports^{7, 8} have shown this to be a determinant of patency of the duct.

These interesting hypotheses, however, cannot explain the data from oriental and Mexican populations^4–7 and their difference from the Caucasian series.³ Different prevalence of specific cardiac malformations amongst ethnic groups was previously reported and explained on the basis of genetic heterogeneity. For example, the subarterial ventricular septal defect is more frequent in the setting of tetralogy of Fallot in the Japanese population⁹ than in Caucasian populations.¹⁰

The cardiac phenotype is the result of many genetic and environmental interactions. In children with Down's syndrome, furthermore, additional genetic^{11, 12} and/or environmental¹³ variants may contribute to cardiac morphogenesis. We might anticipate, therefore, that ethnic genetic factors could also change the prevalence of types of cardiac defects in children with major genetic defects.¹⁴ If this were the case, it could help to explain the incomplete correlations between genotype and phenotype, and the significant phenotypic variability observed in patients with genetic syndromes. It could also prompt a search for additional modifying genetic or environmental factors involved in cardiac morphogenesis.