Double aortic arch with double aneuploidy—rare anomaly in combined Down and Klinefelter syndrome

Aneuploidy is defined as an abnormal number of chromosomes. Double aneuploidy, the existence of two chromosomal abnormalities in the same person, is relatively rare. It can involve both autosomal (chromosome 13, 18 or 21) and sex chromosomes [17] and each may manifest either as a monosomy or trisomy or even tetra- or pentasomy.

The incidence of a double aneuploidy with DS and KS varies in different publications [11]. Kovaleva and Mutton [12] have reported that 0.098% of the children with DS also have KS.

The incidence and spectrum of cardiovascular anomalies in children born with Down–Klinefelter syndrome is not known. Only four case reports on CHD in these patients have been published [2, 6, 7, 11], but none had a double aortic arch.

Adult patients with isolated KS may occasionally suffer from mitral valve prolapse. However, an obvious relationship between this syndrome and CHD has not been documented, with exception of several case reports [1, 15]. In contrast, Down syndrome alone is well known for cardiac anomalies, occurring in 40% to 50% of patients [13]. Freeman [9] reported a 44% incidence of CHD in a group of 227 infants with DS, of which 45% are atrioventricular, 35% are ventricular and 8% had an isolated atrial septal defect. The resting 12% of other anomalies did not include any infant with a vascular ring. As a matter of fact, an aberrant origin of the subclavian artery (arteria lusoria) seems to be found more and more frequently in children with DS, so that it has even been proposed to consider it as a new cardiac sign for DS [5]. In most of them, however, this should be only an incidental finding [14], not responsible for the feeding difficulties. Interestingly, in patients with DS less vascular anomalies than in general population were reported, probably because of an increase in inhibitors of vascular endothelial growth factor, whose genes are located on chromosome 21 [10]. Double aortic arch does not belong to the spectrum of defects known to be associated with DS.

Our observation should draw attention to a possible occurrence of a complete vascular ring in a young infant with clinical symptoms of recurrent respiratory and feeding problems and a (double) aneuploidy. In addition to assessing intracardiac anatomy, a careful assessment of aortic arch anatomy is warranted [3, 4, 16] before possible breathing or swallowing difficulties may be assigned to muscular hypotony, bronchial pathology and other factors, common for patients with (double) aneuploidies.