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

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

Affiliations
  • 1Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. wonspark@skku.edu
  • 2Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.
  • 3Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. changski@skku.edu

Abstract

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.

Keyword

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

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/*genetics/therapy
Pulmonary Alveoli/*abnormalities
Pulmonary Veins/*abnormalities
Republic of Korea
Sequence Analysis
Forkhead Transcription Factors

Figure

  • Fig. 1 (A) Chest radiograph at 2 hours of life showing bilateral pneumothorax. (B) After C-tube insertion.

  • Fig. 2 Histopathologic findings of the deceased newborn with alveolar capillary dysplasia with misalignment of pulmonary veins. (A and B) Malpositioned pulmonary vein branches within the same adventitial sheath with adjacent pulmonary arteries. (C) Masson's trichrome stain highlighting the same adventitial sheath. (D) Improperly positioned capillaries within the walls of the alveoli away from the alveolar epithelium.

  • Fig. 3 Sequence analysis of FOXF1. The patient was heterozygous for a novel missense variant (c.305T>C, p.Leu102Pro; arrow) in FOXF1. Neither of the parents had the pathogenic variant.


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