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FOX gene cluster defects in alveolar capillary dysplasia associated with congenital heart disease

  • Daniela Laux (a1), Valérie Malan (a2), Fanny Bajolle (a1), Younes Boudjemline (a1), Jeanne Amiel (a3) and Damien Bonnet (a1)...
Abstract Objective

The objective was to report two new patients with the diagnosis of alveolar capillary dysplasia and congenital heart disease, to describe the associated cardiac defects seen in these cases and in the literature, and to consider recent genetic advances concerning the FOX transcription factor gene cluster in chromosome 16q24.1q24.2.


We retrospectively analysed the records of all patients with congenital heart disease and alveolar capillary dysplasia seen in the Pediatric Cardiology Department between 2005 and 2010. We reviewed all literature published in the English language relating to cases of alveolar capillary dysplasia and congenital heart disease.


Two infants with alveolar capillary dysplasia and cardiac malformation were identified: one had an atrioventricular septal defect and a de novo balanced reciprocal translocation t(1;16)(q32;q24), the second infant had a ventricular septal defect. Analysis of 31 cases of the literature including these new cases showed a predominant association of alveolar capillary dysplasia with obstructive left heart disease (35%), as well as an atrioventricular septal defect (29%). FOX gene cluster defects were identified in eight of these patients.


Genetic background of alveolar capillary dysplasia is discussed in the light of the balanced reciprocal translocation t(1;16)(q32;q24) identified in the first child of this report. Alveolar capillary dysplasia should be suspected in neonates with congenital heart disease and unexpectedly elevated pulmonary vascular resistances, especially in cases of obstructive left heart disease or atrioventricular septal defect. Detecting FOX gene cluster defects should be considered in infants with alveolar capillary dysplasia with or without congenital heart disease.

Corresponding author
Correspondence to: Pr D. Bonnet, MD, PhD, Necker-M3C, Department of Pediatric Cardiology, Hôpital Necker-Enfants-Malades, Université Paris Descartes, AP-HP, 149, rue de Sèvres, 75015 Paris, France. Tel: 33 1 44 49 43 44; Fax: 33 1 44 49 43 40; E-mail:
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1. CG Janney , FB Askin , C Kuhn III. Congenital alveolar capillary dysplasia – an unusual cause of respiratory distress in the newborn. Am J Clin Pathol 1981; 76: 722727.

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15. F Pasutto , H Sticht , G Hammersen , et al. Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia and mental retardation. Am J Hum Genet 2007; 80: 550560.

17. P Stankiewicz , P Sen , SS Bhatt , et al. Genomic and genic deletions of the fox gene cluster on 16q241 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations. Am J Hum Genet 2009; 84: 780791.

19. F Zufferey , D Martinet , MC Osterheld , et al. 16q24.1 microdeletion in a premature newborn: usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn. Pediatr Crit Care Med 2011; 12: e427e432.

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Cardiology in the Young
  • ISSN: 1047-9511
  • EISSN: 1467-1107
  • URL: /core/journals/cardiology-in-the-young
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