Rapid genome diagnosis of alveolar capillary dysplasia leading to treatment in a child with respiratory and cardiac failure

Cold Spring Harb Mol Case Stud. 2024 Jan 10;9(4):a006292. doi: 10.1101/mcs.a006292. Print 2023 Dec.

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.

Keywords: pulmonary hypoplasia; respiratory insufficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Heart Failure* / diagnosis
  • Heart Failure* / genetics
  • Heart Failure* / therapy
  • Humans
  • Hypertension, Pulmonary* / complications
  • Hypertension, Pulmonary* / pathology
  • Infant, Newborn
  • Lung / pathology
  • Male
  • Persistent Fetal Circulation Syndrome* / diagnosis
  • Persistent Fetal Circulation Syndrome* / genetics
  • Persistent Fetal Circulation Syndrome* / therapy
  • Pulmonary Alveoli / abnormalities*

Supplementary concepts

  • Alveolar capillary dysplasia