Pulmonary hypertension in patients carrying FLNA loss-of-function variants

<bold>Introduction:</bold> Case of pulmonary hypertension (PH) occurring in loss-of-fonction <italic>FLNA</italic> variants have been described, however the characteristics and outcomes of those patients are unknown. <bold>Methods:</bold> We reported clinical, functional, radiologic, and hemodynamic characteristics in patients with <italic>FLNA</italic> loss-of-function variants and PH from the French PH Network. <bold>Results:</bold> Nine patients were identified with a female to male ratio of 8:1. PH was diagnosed at a median age of 36 years ⌈0-69⌉. At baseline, 5 patients were in NYHA-FC I-II, 2 patients were in NYHA-FC III, and 2 patients in NYHA-FC IV. Pulmonary tests showed an airway obstruction in 5/9 patients and DLCO was decreased for all with a median value of 48% ⌈22-64⌉. Hemodynamic parameters showed precapillary PH with a median mPAP of 33 ⌈22-49⌉mmhg, a normal PAWP of 9 ⌈5-11⌉mmHg, and increased PVR of 4.7 ⌈2.4-8.0⌉WU. Five patients were assessed for NO acute vasodilator response and two were positive. Reassessement after initiation of oral PAH-approved drugs was in 4 patients showing no significant improvement. Five patients (56%) had drug-refractory epilepsy and Brain MRI uncovered periventricular nodular heterotopia in six patients (70%). Three patients (33%) had a concurrent congenital heart disease and an aneurysmal dilatation of the sinus of Valsalva was reported in four patients (44%). All patients exhibited scanographic ventilatory disorders and present anomalies suggestive of an underlying pathology present in 88,9%. <bold>Conclusion:</bold> This study confirms the possible onset of PH in patients carrying <italic>FLNA</italic> mutations and should prompt genetic screening for <italic>FLNA,</italic> particulary in female patients presenting with epilepsy, pulmonary emphysema, and/or aortic malformation.