Heterogeneous Pulmonary Phenotypes in Filamin A Mutation-Related Lung Disease

Interstitial lung disease (ILD) has been recently reported in a few patients with pathogenic variants in the Filamin A (FLNA) gene with variable presentation and prognosis. This study evaluated the respiratory manifestations and clinical features in children with FLNA disease. We conducted a retrospective review of pediatric patients with variants in FLNA in a tertiary children's hospital. The clinical features, genotype, management, and outcomes were analyzed. We identified 9 patients with variants in FLNA aged 15 months to 24 years, 4 females and 5 males. Six patients had abnormal chest imaging ranging from mild interstitial prominence to atelectasis, interstitial densities, and hyperinflation. Three patients with ILD presented during the neonatal period or early infancy with respiratory distress or respiratory failure requiring supplemental oxygen or assisted ventilation via tracheostomy. We report male twins with the same FLNA variant and lung disease, but different ages and clinical features at presentation eventually culminating in respiratory failure requiring assisted ventilation. All patients had FLNA variants identified by FLNA sequencing, had abnormal echocardiograms, and none of the patients underwent lung biopsy or lung transplantation. The outcomes were variable and could be as severe as chronic respiratory failure. The wide spectrum of respiratory manifestations and abnormal chest imaging in our study highlights the importance of evaluation for lung disease in patients with variants in FLNA. FLNA sequencing in suspected cases with ILD may obviate the need for a lung biopsy, prompt surveillance for progressive lung disease, and evaluation for associated clinical features.