A novel mutation in FOXF1 gene associated with alveolar capillary dysplasia with misalignment of pulmonary veins, intestinal malrotation and annular pancreas

Neonatology. 2013;103(4):241-5. doi: 10.1159/000346062. Epub 2013 Feb 12.


Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, fatal, neonatal developmental lung disorder, which usually presents as persistent pulmonary hypertension unresponsive to treatment. The authors report the case of a neonate with persistent pulmonary hypertension, associated with duodenal stenosis secondary to annular pancreas and intestinal malrotation. Support treatment, inhaled nitric oxide, oral sildenafil and nebulized iloprost were used with no clinical improvement. The neonate presented an overwhelming course, with hypoxemia refractory to treatment. At autopsy lung histology showed the characteristic features of ACD/MPV. DNA sequence analysis revealed a heterozygous nonsense mutation c.539C>A;p.S180X, in the first exon of FOXF1. FOXF1 has been identified as one of the genes responsible for ACD/MPV associated with multiple congenital malformations. This clinical case is the first report of a heterozygous nonsense mutation c.539C>A;p.S180X in the first exon of FOXF1, in a patient with ACD/MPV associated with annular pancreas and intestinal malrotation.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple*
  • Autopsy
  • Codon, Nonsense*
  • DNA Mutational Analysis
  • Digestive System Abnormalities
  • Exons
  • Fatal Outcome
  • Female
  • Forkhead Transcription Factors / genetics*
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Infant, Newborn
  • Intestinal Volvulus / congenital*
  • Intestinal Volvulus / diagnosis
  • Intestinal Volvulus / genetics
  • Intestinal Volvulus / therapy
  • Lung / pathology
  • Pancreas / abnormalities*
  • Pancreatic Diseases / diagnosis
  • Pancreatic Diseases / genetics*
  • Pancreatic Diseases / therapy
  • Persistent Fetal Circulation Syndrome / diagnosis
  • Persistent Fetal Circulation Syndrome / genetics*
  • Persistent Fetal Circulation Syndrome / therapy
  • Phenotype
  • Pulmonary Alveoli / abnormalities*


  • Codon, Nonsense
  • FOXF1 protein, human
  • Forkhead Transcription Factors

Supplementary concepts

  • Alveolar capillary dysplasia
  • Annular pancreas
  • Volvulus Of Midgut