Hermann Ruben, Shovlin Claire L, Kasthuri Raj S, Serra Marcelo, Eker Omer F, Bailly Sabine, Buscarini Elisabetta, Dupuis-Girod Sophie
ENT department, Hôpital E Herriot, Hospices Civils de Lyon, Lyon, France.
European Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HHT Rare Disease Working Group, Paris, France.
Nat Rev Dis Primers. 2025 Jan 9;11(1):1. doi: 10.1038/s41572-024-00585-z.
Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia inherited as an autosomal dominant trait and caused by loss-of-function pathogenic variants in genes encoding proteins of the BMP signalling pathway. Up to 90% of disease-causal variants are observed in ENG and ACVRL1, with SMAD4 and GDF2 less frequently responsible for HHT. In adults, the most frequent HHT manifestations relate to iron deficiency and anaemia owing to recurrent epistaxis (nosebleeds) or bleeding from gastrointestinal telangiectases. Arteriovenous malformations (AVMs) in the lungs, liver and the central nervous system cause additional major complications and often complex symptoms, primarily due to vascular shunting, which is right-to-left through pulmonary AVMs (causing ischaemic stroke or cerebral abscess) and left-to-right through systemic AVMs (causing high cardiac output). Children usually experience isolated epistaxis; in rare cases, childhood complications occur from large AVMs in the lungs or central nervous system. Management goals encompass control of epistaxis and intestinal bleeding from telangiectases, screening for and treatment of iron deficiency (with or without anaemia) and AVMs, genetic counselling and evaluation of at-risk family members. Novel therapeutics, such as systemic antiangiogenic therapies, are actively being investigated. Although HHT is associated with increased morbidity, the appropriate screening and treatment of visceral AVMs, and the effective management of bleeding and anaemia, improves quality of life and overall survival.
遗传性出血性毛细血管扩张症（HHT）是一种以常染色体显性性状遗传的血管发育异常疾病，由编码骨形态发生蛋白（BMP）信号通路蛋白的基因功能丧失性致病变异引起。高达90%的致病基因变异见于ENG和ACVRL1，而SMAD4和GDF2导致HHT的情况较少见。在成年人中，HHT最常见的表现与因反复鼻出血或胃肠道毛细血管扩张出血导致的缺铁和贫血有关。肺、肝和中枢神经系统的动静脉畸形（AVM）会引发其他主要并发症，并常伴有复杂症状，主要是由于血管分流，即通过肺动静脉畸形从右向左分流（导致缺血性中风或脑脓肿），以及通过体循环动静脉畸形从左向右分流（导致高心输出量）。儿童通常仅出现鼻出血；在极少数情况下，儿童会因肺部或中枢神经系统的大型动静脉畸形而出现并发症。治疗目标包括控制鼻出血和毛细血管扩张引起的肠道出血、筛查和治疗缺铁（伴或不伴贫血）及动静脉畸形、遗传咨询以及对高危家庭成员进行评估。新型治疗方法，如全身抗血管生成疗法，正在积极研究中。尽管HHT与发病率增加有关，但对内脏动静脉畸形进行适当的筛查和治疗，以及有效管理出血和贫血，可改善生活质量和总体生存率。
