Abstract Introduction Interstitial lung disease (ILD) in infants represents a rare and heterogeneous group of disorders distinct from those occurring in adults in both clinical diagnosis and progression. Emerging evidence has recognized filamin A (FLNA) mutation-associated lung disease as a distinct form of pediatric ILD. FLNA mutations result in abnormal cytoskeletal function and present with a diverse spectrum of developmental, neurologic, gastrointestinal, cardiac, vascular, and pulmonary abnormalities. Here, we present a child with persistent hypoxemia with comorbid congenital heart disease (CHD), pulmonary hypertension (PH), and dysphagia. Case Presentation A full-term female with dysphagia, PH, patent ductus arteriosus (PDA) and bidirectional ventricular septal defect (VSD) underwent surgical VSD patch closure, atrial septum fenestration, tricuspid valvuloplasty and PDA ligation at 4 months old. Computed tomography (CT) imaging of the lungs prior to VSD repair demonstrated bilateral ground glass opacities (GGO) with mosaic attenuation which was attributed to pulmonary overcirculation (Fig 1). Post-operatively, she experienced persistent tachypnea and intermittent hypoxemia which did not completely resolve with medical management of PH using sildenafil and ambrisentan and initiation of enteral tube feeding for dysphagia. Over the subsequent 6 months, she remained on low-flow supplemental oxygen at home but required hospitalization for acute-on-chronic respiratory failure on three occasions for viral bronchiolitis with worsening PH during acute illnesses. Due to prior findings of GGO and mosaic attenuation on CT, she received a three-day steroid pulse during prolonged illness without significant response. Genetic evaluation and repeat CT chest were recommended; imaging redemonstrated prior findings with new diffuse cystic changes in a honeycomb appearance concerning for ILD (Fig 1). Whole genome sequencing ultimately revealed a pathogenic variant in the FLNA gene at p.R863* with X-linked inheritance pattern, consistent with her constellation of FLNA-associated anomalies including CHD, PH, feeding difficulties and ILD. Discussion This case highlights the importance of maintaining a broad differential in a patient with CHD, PH and dysphagia experiencing persistent respiratory symptoms after appropriate medical and surgical management. Genetic evaluation is a useful tool in investigating for a unifying diagnosis in patients with multiple organ system involvement. FLNA-associated ILD is a rare, but increasingly recognized, disorder within the spectrum of childhood ILD with phenotypes ranging from mild respiratory insufficiency to progressive cystic or fibrotic lung disease. The patient’s specific variant has not been well described in association with ILD, but the radiographic pattern, chronic hypoxemia and variable responsiveness to systemic steroids are consistent with the described spectrum of FLNA-associated ILD. This abstract is funded by: None
Sawhney et al. (Fri,) studied this question.