A Novel De Novo Pathogenic Variant in FOXF1 in a Newborn with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins

Yonsei Med J. 2017 May;58(3):672-675. doi: 10.3349/ymj.2017.58.3.672.


Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is an autosomal dominant, fatal developmental disorder of the lungs, with a mortality rate of about 100%. ACD/MPV is caused by mutations in FOXF1. Herein, we describe a newborn boy with ACD/MPV carrying a novel pathogenic variant of FOXF1. The patient developed respiratory distress and severe pulmonary hypertension on the first day of life. Despite aggressive cardiorespiratory management, including veno-venous extracorporeal membrane oxygenation, his condition deteriorated rapidly, and he died within the first month of his life. Lung histology showed the characteristic features of ACD/MPV at autopsy. Sequence analysis of FOXF1 from genomic DNA obtained from autopsied lung tissue revealed that the patient was heterozygous for a novel missense variant (c.305T>C; p.Leu102Pro). Further analysis of both parents confirmed the de novo occurrence of the variant. To the best of our knowledge, this is the first report of genetically confirmed ACD/MPV in Korea.

Keywords: Alveolar capillary dysplasia with misalignment of pulmonary veins; FOXF1; Korean; pathogenic; variant.

Publication types

  • Case Reports

MeSH terms

  • DNA Mutational Analysis
  • Forkhead Transcription Factors / genetics*
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Infant, Newborn
  • Lung / pathology*
  • Male
  • Mutation
  • Mutation, Missense / genetics*
  • Persistent Fetal Circulation Syndrome / diagnosis
  • Persistent Fetal Circulation Syndrome / genetics*
  • Persistent Fetal Circulation Syndrome / therapy
  • Pulmonary Alveoli / abnormalities*
  • Pulmonary Veins / abnormalities*
  • Republic of Korea
  • Sequence Analysis


  • Forkhead Transcription Factors

Supplementary concepts

  • Alveolar capillary dysplasia