Two patients with FOXF1 mutations with alveolar capillary dysplasia with misalignment of pulmonary veins and other malformations: Two different presentations and outcomes

Am J Med Genet A. 2018 Dec;176(12):2877-2881. doi: 10.1002/ajmg.a.40641. Epub 2018 Oct 31.

Abstract

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) describes a group of developmental disorders affecting the lungs with its pulmonary vasculature. Mutations in the FOXF1 gene have been reported in most cases, and extrapulmonary findings were described. We present two patients with ACDMPV and FOXF1 mutations that illustrate the variability in presentation and outcome of their disease. Patient 1 was a full-term infant with imperforate anus and pulmonary hypertension. He required Extracorporeal Membrane Oxygenation on day of life (DOL) 3, and passed away on DOL 13 after no clinical improvement. Postmortem findings were consistent with ACDMPV. FOXF1 testing revealed a heterozygous pathogenic frameshift de novo mutation, c.1057_1078dup, p.(Gly360Valfs*58). Patient 2 is a 6-month-old female, with a small omphalocele. She had intermittent retractions at 1 week of age. She was admitted with pulmonary hypertension at 7 weeks of age. Lung biopsy confirmed ACDMPV. FOXF1 testing revealed a de novo, heterozygous likely pathogenic missense mutation c.253T>C, p.(Phe85Leu]). Our two patients had different presentations, ages of onset, and progression of their disease. Our second patient had patchy lung involvement on biopsy, which may explain the relatively delayed onset and longer survival. ACDMPV is an important consideration for full-term infants with worsening pulmonary hypertension early in life.

Keywords: FOXF1; alveolar capillary dysplasia with misalignment of pulmonary veins; pulmonary hypertension.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics*
  • Autopsy
  • Biomarkers
  • Biopsy
  • Comparative Genomic Hybridization
  • Cytogenetic Analysis
  • Echocardiography
  • Female
  • Forkhead Transcription Factors / genetics*
  • Genetic Association Studies
  • Humans
  • Infant
  • Male
  • Mutation*
  • Persistent Fetal Circulation Syndrome / diagnosis*
  • Persistent Fetal Circulation Syndrome / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Pulmonary Alveoli / abnormalities*
  • Pulmonary Veins / abnormalities*

Substances

  • Biomarkers
  • FOXF1 protein, human
  • Forkhead Transcription Factors

Supplementary concepts

  • Alveolar capillary dysplasia