Dana R. Tower1, Ronald W. Day2, Tighe Marrone3, Rachel Palmquist4,5, Lincoln D. Nadauld6, Joshua L. Bonkowsky4,5,8 and Sabrina Malone Jenkins5,7,8 1Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA; 2Division of Pediatric Cardiology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA; 3Division of Pediatric Critical Care, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA; 4Division of Pediatric Neurology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA; 5Center for Personalized Medicine, Primary Children's Hospital, Intermountain Healthcare, Salt Lake City, Utah 84113, USA; 6Intermountain Precision Genomics, Intermountain Healthcare, St. George, Utah 84790, USA; 7Division of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA Corresponding authors: Joshua.bonkowskyhsc.utah.edu; sabrina.malonejenkinshsc.utah.edu Abstract

Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure. He had a complicated hospital course resulting in cardiac arrest and requirement for extracorporeal membrane oxygenation. Computed tomography of the chest showed a heterogenous pattern of interlobular septal thickening and pulmonary edema. The etiology of his condition was unknown, lung biopsy was contraindicated because of his medical fragility, and discussions were held to move to palliative care. Rapid whole-genome sequencing (rWGS) was performed. In 2 d it resulted, revealing a novel FOXF1 gene pathogenic variant that led to the presumptive diagnosis of atypical ACD. Cases of atypical ACD have been reported with survival in patients using medical therapy or lung transplantation. Based on the rWGS diagnosis and more favorable potential of atypical ACD, aggressive medical treatment was pursued. The patient was discharged home after 67 d in the hospital; he is currently doing well more than 30 mo after his initial presentation with only one subsequent hospitalization and no requirement for lung transplantation. Our case reveals the potential for use of rWGS in a critically ill child in which the diagnosis is unknown. rWGS and other advanced genetic tests can guide clinical management and expand our understanding of atypical ACD and other conditions.

Received April 28, 2023. Accepted August 4, 2023.