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Review
. 2021 Mar;56(3):621-629.
doi: 10.1002/ppul.24687. Epub 2020 Feb 12.

Pulmonary hypertension in children with Down syndrome

Douglas Bush  1 , Csaba Galambos  2 , David Dunbar Ivy  3
Affiliations
Review

Pulmonary hypertension in children with Down syndrome

Douglas Bush et al. Pediatr Pulmonol. 2021 Mar.

Abstract

Individuals with Down syndrome (DS) have an increased risk of developing pulmonary hypertension (PH). In this review, we explore the epidemiology and clinical characteristics of PH in the population with DS and examine genetic, molecular and clinical contributions to the condition. The presence of an additional copy of chromosome 21 (trisomy 21) increases the risk of developing PH in children with DS through many mechanisms, including increased hemodynamic stress in those with congenital heart disease, hypoxemia through impaired ventilation to perfusion matching secondary to developmental lung abnormalities, pulmonary hypoplasia from pulmonary vascular endothelial dysfunction, and an increase in pulmonary vascular resistance often related to pulmonary comorbidities. We review recent studies looking at novel biomarkers that may help diagnose, predict or monitor PH in the population with DS and examine current cardiopulmonary guidelines for monitoring children with DS. Finally, we review therapeutic interventions specific to PH in individuals with DS. Contemporary work has identified exciting mechanistic pathways including the upregulation of antiangiogenic factors and interferon activity, which may lead to additional biomarkers or therapeutic opportunities. Throughout the manuscript, we identify gaps in our knowledge of the condition as it relates to the population with DS and offer suggestions for future clinical, translational, and basic science research.

Keywords: Down syndrome; pulmonary arterial hypertension; pulmonary hypertension; trisomy 21.

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References

REFERENCES

    1. Bush D, Galambos C, Ivy DD, Abman SH, Wolter-Warmerdam K, Hickey F. Clinical characteristics and risk factors for developing pulmonary hypertension in children with down syndrome. J Pediatr. 2018;202:212-219.
    1. O'Leary L, Hughes-McCormack L, Dunn K, Cooper SA. Early death and causes of death of people with down syndrome: a systematic review. J Appl Res Intellect Disabil. 2018;31(5):687-708.
    1. Yang Q, Rasmussen SA, Friedman JM. Mortality associated with down's syndrome in the USA from 1983 to 1997: a population-based study. Lancet. 2002;359(9311):1019-1025.
    1. Espinola-Zavaleta N, Soto ME, Romero-Gonzalez A, et al. Prevalence of congenital heart disease and pulmonary hypertension in down's syndrome: an echocardiographic study. J Cardiovasc Ultrasound. 2015;23(2):72-77.
    1. Duffels MG, Engelfriet PM, Berger RM, et al. Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a dutch registry. Int J Cardiol. 2007;120(2):198-204.

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