Abstract Introduction Filamin A (FLNA) is a large, ubiquitous actin-binding protein crucial for cytoskeletal organization. FLNA-related disorders are X-linked conditions caused by pathogenic variants in the FLNA gene and encompass a broad spectrum of phenotypes, depending on whether the variant results in loss or gain of function. Gain-of-function variants are associated with skeletal dysplasia syndromes, whereas loss-of-function variants are linked to periventricular nodular heterotopia (PVNH), and a spectrum of cardiovascular, connective tissue, and pulmonary manifestations. Reported pulmonary manifestations include alveolar hypoplasia, emphysema, asthma, interstitial lung disease and pulmonary hypertension. However, intrapulmonary shunt and pulmonary arteriovenous malformations (PAVMs) have not been previously reported in FLNA deficiency. Description A woman in her early 30s with FLNA-related PVNH, epilepsy, vertebral artery stenosis, mitral valve disease and a recent midbrain stroke presented with progressive exertional dyspnea and cyanosis. Transthoracic echocardiography revealed posterior mitral leaflet prolapse and a delayed positive bubble study, suggestive of an intrapulmonary shunt. Transcranial Doppler confirmed a grade II right-to-left shunt. Right heart catheterization demonstrated precapillary pulmonary hypertension with right atrial pressure of 12 mm Hg, mean pulmonary artery pressure of 27 mm Hg, pulmonary artery occlusion pressure of 15 mm Hg, cardiac output was 5.65 L/min and cardiac index 3.5 L/min/m², pulmonary vascular resistance of 2.65 Wood units. Chest computerized tomography showed no parenchymal abnormalities but hyperinflated lungs with air trapping. Intracardiac echocardiography with agitated saline demonstrated microbubbles entering the left atrium from a distal left pulmonary artery, suggestive of an intrapulmonary shunt. Pulmonary angiography demonstrated serpiginous left lower lobe and lingular branches with preserved caliber compared to the upper lobe branches (Figure 1). Discussion The coexistence of intrapulmonary shunting and pulmonary hypertension in this patient represents a previously unrecognized pulmonary vascular phenotype associated with FLNA deficiency, potentially due to microscopic PAVMs or intrapulmonary vascular dilatations. Recognition of this association has clinical implications, including hypoxemia and risk of paradoxical embolization through right-to-left shunting. This novel finding expands the pulmonary vascular phenotype of FLNA mutations and highlights the need for vigilance for vascular malformations in affected patients. This abstract is funded by: None
Gonzalez-Ibarra et al. (Fri,) studied this question.