Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
Department of Pathology and Laboratory Medicine, University of Colorado School of Medicine, Aurora, Colorado.
Pediatr Pulmonol. 2021 Mar;56(3):621-629. doi: 10.1002/ppul.24687. Epub 2020 Feb 12.
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.
唐氏综合征（DS）患者发生肺动脉高压（PH）的风险增加。本文探讨了 DS 人群中 PH 的流行病学和临床特征，并研究了导致该疾病的遗传、分子和临床因素。第 21 号染色体（三体 21）的额外拷贝通过多种机制增加了 DS 患儿发生 PH 的风险，包括先天性心脏病患儿的血流动力学压力增加、肺血管内皮功能障碍导致的通气/灌注匹配受损引起的低氧血症、以及肺动脉阻力增加，这通常与肺部合并症有关。本文回顾了近期研究中用于诊断、预测或监测 DS 人群 PH 的新型生物标志物，并研究了目前针对 DS 患儿监测的心肺指南。最后，本文综述了 DS 患者 PH 的特定治疗干预措施。目前的研究已经确定了一些令人兴奋的发病机制途径，包括抗血管生成因子和干扰素活性的上调，这可能为进一步的生物标志物或治疗机会提供依据。本文通篇指出了与 DS 人群相关的 PH 认识空白，并为未来的临床、转化和基础科学研究提供了建议。
