Department of Pediatrics, Irving Medical Center, Columbia University, 1150 St. Nicholas Avenue, New York, NY 10032, USA.
Department of Medicine, Irving Medical Center, Columbia University, 622 W 168th St, New York, NY 10032, USA.
Genes (Basel). 2020 Oct 16;11(10):1213. doi: 10.3390/genes11101213.
Pulmonary arterial hypertension (PAH) is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors and likely gene-environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to ~42% of pediatric-onset PAH compared to ~12.5% of adult-onset PAH. De novo variants are frequently associated with PAH in children and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, increased etiologic heterogeneity, poorer prognosis, and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.
肺动脉高压（PAH）是一种罕见疾病，尽管最近有了治疗进展，但死亡率仍然很高。这种疾病是由遗传和环境因素以及可能的基因-环境相互作用引起的。虽然 PAH 可以在整个生命周期中表现出来，但儿童发病的疾病尤其具有挑战性，因为它通常与更严重的临床过程和合并症有关，包括肺/心脏发育异常。鉴于这些差异，儿童发病 PAH 的遗传研究中出现的新数据表明，遗传基础与成人不同，这也许并不奇怪。儿童的遗传负担更大，罕见的遗传因素导致约 42%的儿童发病 PAH，而成人发病 PAH 约为 12.5%。新生变体在儿童中经常与 PAH 相关，至少占所有儿科病例的 15%。儿科 PAH 患者的医疗标准是基于对成人数据的推断。然而，儿童发病 PAH 的病因异质性增加、预后较差和遗传负担增加，需要制定专门的儿科研究议程，以改善分子诊断和临床管理。基于基因组学的方法将提高对儿科 PAH 的理解，以及它与其他罕见儿科遗传疾病的关系。
