FOXF1 Transcription Gene Testing in a Case of Late Presentation Alveolar Capillary Dysplasia

Abstract

INTRODUCTION: Alveolar capillary dysplasia (ACD) is a rare, fatal developmental lung disorder that typically presents with respiratory failure and pulmonary hypertension in neonates. Until recently, lung biopsy provided the only means of definitive diagnosis and remains the gold standard. Blood testing is now available for mutations in the FOXF1 transcription gene isolated in 40% of cases. We describe a case of late presentation ACD with genetic testing supporting the diagnosis in a term infant who presented with symptoms at 2 months of age. CASE PRESENTATION: Our patient presented to an outside emergency department with respiratory distress. On admission to our pediatric intensive care unit (PICU), she became increasingly hypoxemic and hemodynamically unstable despite inotropic and ventilator support. She ultimately required extracorporeal membrane oxygenation support from day 2 through 13. Lung biopsy was considered but not performed because of high risk of bleeding. Echocardiogram showed severe pulmonary hypertension with significant right ventricle dilatation of unknown etiology. During hospitalization, she was treated with nitric oxide, sildenafil, and bosentan without improvement. Due to persistence of pulmonary hypertension, the FOXF1 test was sent on day 40. Tracheostomy was performed because of the inability to wean off vent support. On day 73, genetic test results became available showing a previously undescribed mutation variant in the FOXF1 transcription gene. Presumed diagnosis of ACD led to discussions with the family about its terminal nature and to the decision to withdraw support. Autopsy results confirmed the diagnosis of ACD. DISCUSSION: ACD typically presents in the newborn period. Diagnosis can be challenging in patients with late presentation. There should be a high index of suspicion in patients with unexplained pulmonary hypertension. Early diagnosis may prevent significant invasive therapies. While the gold standard for diagnosis remains lung biopsy, it may not be feasible depending on the clinical status of the patient. CONCLUSION(S): Early testing for FOXF1 transcription gene mutation may be useful as a minimally invasive method of obtaining the diagnosis of ACD in cases of unexplained persistent pulmonary hypertension.