Hypertensive pulmonary vascular disease in Down syndrome

Clinical studies have suggested that patients with Down syndrome have precocious development of pulmonary hypertension, even in the absence of congenital heart disease. To examine the pathologic basis of this impression, we studied 82 patients with Down syndrome autopsied at The Johns Hopkins Hospital from 1913 to present. The patients ranged in age from 26 hours to 25 years; 41 (50%) were female. Atrioventricular canal defect was present in 40 patients, nine of whom also had pulmonary stenosis. Eight had isolated ventricular septal defect and seven had other malformations. Histologic sections of the lung from each patient were studied and the degree of hypertensive pulmonary vascular disease graded. Age and sex-matched controls without cardiovascular manifestations, all other autopsied patients with atrioventricular canal defect not associated with Down syndrome, and age-matched patients with ventricular septal defect or other malformations were similarly studied for pulmonary vascular changes. Comparison of the 27 patients with Down syndrome and no cardiovascular malformations with normal controls showed no differences, with one notable exception: an 8-month-old child with Down syndrome had severe HPVD secondary to idiopathic pulmonary hypertension. HPVD in patients with the various cardiovascular malformations was similar for those groups with Down syndrome and those without, when HPVD was considered as a function of the patients' age and the type of malformation. We conclude that, in general, patients with Down syndrome have no predisposition to develop severe or precocious hypertensive pulmonary vascular disease.