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

Published online by Cambridge University Press:  21 January 2013

Daniela Laux
Department of Pediatric Cardiology, Centre de Référence «Malformations cardiaques Congénitales Complexes-M3C»
Valérie Malan
Department of Cytogenetics, Hôpital Necker-Enfants-Malades, Université Paris Descartes, Paris, France
Fanny Bajolle
Department of Pediatric Cardiology, Centre de Référence «Malformations cardiaques Congénitales Complexes-M3C»
Younes Boudjemline
Department of Pediatric Cardiology, Centre de Référence «Malformations cardiaques Congénitales Complexes-M3C»
Jeanne Amiel
Department of Clinical Genetics, Hôpital Necker-Enfants-Malades, Université Paris Descartes, Paris, France
Damien Bonnet*
Department of Pediatric Cardiology, Centre de Référence «Malformations cardiaques Congénitales Complexes-M3C»
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:



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.

Original Articles
Copyright © Cambridge University Press 2013 

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