BACKGROUND Pulmonary hypertension (PH) is an unusual complication of X-linked disease caused by loss-of-function (LOF) variants in the filamin A (FLNA) gene. Patients with FLNA LOF may also present dysmorphic facial features, aortic dilation, thrombopenia, and periventricular nodular heterotopia (PVNH). METHODS We reported clinical, functional, radiologic, and hemodynamic characteristics of patients with FLNA LOF variants and PH from the French PH Network. RESULTS Nine patients were identified with a female to male ratio of 8:1. PH was diagnosed at a median age of 36 [0-69] years. Associated conditions included epilepsy (n=5), PVNH (n=7), valvular heart disease (n=8), congenital heart diseases (n=4), thrombocytopenia (n=4), and hyperlaxity (n=4). Right heart catheterisation confirmed moderate-to-severe precapillary PH with a median mPAP of 33 [22-49] mmHg and PVR of 4.7 [2.4-8.0] WU. The DLCO was markedly decreased (48 [22-64] %pred) and five patients had obstructive ventilatory disorder. High-resolution CT showed heterogeneous parenchyma (n=8), emphysema (n=3), presence of a peripheral hyperclear band (n=3) and aortic ectasia (n=4). Pathologic assessment available in one patient revealed significant remodelling of small pulmonary arteries, interstitial edema, and irregular alveoli shapes. During follow-up, three patients died, including two from right heart failure. No patient died from aortic rupture. CONCLUSIONS Precapillary PH, likely due to multiple mechanisms, may complicate the course of patients with LOF FLNA variants and may be the presenting symptom leading to diagnosis. The combination of PH with parenchymal involvement and extrapulmonary symptoms (epilepsy, congenital heart diseases, valvular and aortic involvement, thrombocytopenia) should prompt genetic screening for FLNA.

中文翻译：

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携带 FLNA 功能丧失变异的患者的肺动脉高压。


背景 肺动脉高压 （PH） 是由细丝蛋白 A （FLNA） 基因的功能丧失 （LOF） 变异引起的 X 连锁疾病的一种罕见并发症。FLNA LOF 患者还可能出现面部畸形、主动脉扩张、血栓形成减少和脑室周围结节异位 （PVNH）。方法 我们报告了来自法国 PH 网络的 FLNA LOF 变异和 PH 患者的临床、功能、放射学和血流动力学特征。结果 9 例患者被确定为男女比为 8：1。PH 的中位诊断年龄为 36 [0-69] 岁。相关疾病包括癫痫 （n=5） 、 PVNH （n=7） 、瓣膜性心脏病 （n=8） 、先天性心脏病 （n=4） 、血小板减少症 （n=4） 和过度松弛 （n=4）。右心导管检查证实中度至重度毛细血管前 PH，中位 mPAP 为 33 [22-49] mmHg，PVR 为 4.7 [2.4-8.0] WU。DLCO 显著降低 （48 [22-64] %pred），5 例患者患有阻塞性通气障碍。高分辨率 CT 显示异质性实质 （n=8）、肺气肿 （n=3）、存在外周超清晰带 （n=3） 和主动脉扩张 （n=4）。1 例患者的病理评估显示小肺动脉显著重塑、间质水肿和不规则肺泡形状。在随访期间，3 例患者死亡，其中 2 例死于右心衰竭。没有患者死于主动脉破裂。结论 毛细血管前 PH 可能由于多种机制，可能使 LOF FLNA 变异患者的病程复杂化，并可能成为导致诊断的首发症状。 PH 伴实质受累和肺外症状（癫痫、先天性心脏病、瓣膜和主动脉受累、血小板减少症）的组合应提示进行 FLNA 的基因筛查。