European Journal of Pediatrics

, Volume 174, Issue 8, pp 1123–1126 | Cite as

A late presenter and long-term survivor of alveolar capillary dysplasia with misalignment of the pulmonary veins

  • Yukie Ito
  • Takuma Akimoto
  • Kazutoshi Cho
  • Masafumi Yamada
  • Mishie Tanino
  • Tomoyuki Dobata
  • Masanori Kitaichi
  • Satoru Kumaki
  • Yoshikazu Kinugawa
Case Report


This report demonstrates a late presenter and long-term survivor (38 months old) of alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) and with a heterozygous frameshift mutation in FOXF1. The mild phenotype may be due to his residual normal lung tissue as demonstrated in the chest computed tomography (CT) and histopathological findings.

Conclusion: We report the longest survivor of ACD/MPV. The mild phenotype is most likely due to the patient’s residual normal lung tissue.

What is Known:

Patients with ACD/MPV uniformly die early in life.

A previously reported case with the same mutation in FOXF1 died at 15 days after birth.

What is New:

The presented case is the longest survivor with this disease.

The patient’s mild phenotype can be explained by his residual normal lung tissue.


ACD/MPV FOXF1 Mild phenotype CT Biopsy 



Alveolar capillary dysplasia with misalignment of the pulmonary veins


Computed tomography


Nitric oxide


Polymerase chain reaction



We thank Dr. Christine Kwan for editing and revising this manuscript.

Conflict of interest

The authors declare no conflict of interest.

Authors’ contribution

YI, TD, SK, and YK treated the patient (YI wrote the manuscript under SK’s supervision, and YK took all responsibility of the therapy). MT and MK made the diagnosis using biopsy samples, and TA identified the FOXF1 mutation. KC and MY were consulted about the patient.


  1. 1.
    Abdallah HI, Karmazin N, Marks LA (1993) Late presentation of misalignment of lung vessels with alveolar capillary dysplasia. Crit Care Med 21:628–630PubMedCrossRefGoogle Scholar
  2. 2.
    Ahmed S, Ackerman V, Faught P, Langston C (2008) Profound hypoxemia and pulmonary hypertension in a 7-month-old infant: late presentation of alveolar capillary dysplasia. Pediatr Crit Care Med 9:e43–e46PubMedCrossRefGoogle Scholar
  3. 3.
    Bishop NB, Stankiewicz P, Steinhorn RH (2011) Alveolar capillary dysplasia. Am J Respir Crit Care Med 184:172–179PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Boggs S, Harris MC, Hoffman DJ, Goel R, McDonald-McGinn D, Langston C, Zackai E, Ruchelli E (1994) Misalignment of pulmonary veins with alveolar capillary dysplasia: affected siblings and variable phenotypic expression. J Pediatr 124:125–128PubMedCrossRefGoogle Scholar
  5. 5.
    Kodama Y, Tao K, Ishida F, Kawakami T, Tsuchiya K, Ishida K, Takemura T, Nakazawa A, Matsuoka K, Yoda H (2012) Long survival of congenital alveolar capillary dysplasia patient with NO inhalation and epoprostenol: effect of sildenafil, beraprost and bosentan. Pediatr Int 54:923–926PubMedCrossRefGoogle Scholar
  6. 6.
    Sato M, Okada Y, Oto T, Minami M, Shiraishi T, Nagayasu T, Yoshino I, Chida M, Okumura M, Date H, Miyoshi S, Kondo T (2014) Registry of the Japanese Society of Lung and Heart-Lung Transplantation: official Japanese lung transplantation report, 2014. Gen Thorac Cardiovasc Surg 62:594–601PubMedCrossRefGoogle Scholar
  7. 7.
    Sen P, Yang Y, Navarro C, Silva I et al (2013) Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain. Hum Mutat 34:801–811PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Shankar V, Haque A, Johnson J, Pietsch J (2006) Late presentation of alveolar capillary dysplasia in an infant. Pediatr Crit Care Med 7:177–179PubMedCrossRefGoogle Scholar
  9. 9.
    Stankiewicz P, Sen P, Bhatt SS et al (2009) Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations. Am J Hum Genet 84:780–791PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Szafranski P, Dharmadhikari AV, Brosens E et al (2013) Small noncoding differentially methylated copy-number variants, including lncRNA genes, cause a lethal lung developmental disorder. Genome Res 23:23–33PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Yukie Ito
    • 1
  • Takuma Akimoto
    • 2
  • Kazutoshi Cho
    • 2
  • Masafumi Yamada
    • 3
  • Mishie Tanino
    • 4
  • Tomoyuki Dobata
    • 1
  • Masanori Kitaichi
    • 5
  • Satoru Kumaki
    • 1
  • Yoshikazu Kinugawa
    • 1
  1. 1.Department of PediatricsTeine Keijinkai HospitalSapporoJapan
  2. 2.Maternity and Perinatal Care CenterHokkaido University HospitalSapporoJapan
  3. 3.Department of PediatricsHokkaido University Graduate School of MedicineSapporoJapan
  4. 4.Department of Cancer PathologyHokkaido University Graduate School of MedicineSapporoJapan
  5. 5.Department of PathologyNational Hospital Organization Kinki-Chuo Chest Medical CenterSakaiJapan

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