Hostname: page-component-8448b6f56d-tj2md Total loading time: 0 Render date: 2024-04-18T23:28:33.168Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  21 January 2013

Daniela Laux ,
Valérie Malan ,
Fanny Bajolle ,
Younes Boudjemline ,
Jeanne Amiel  and
Damien Bonnet
Daniela Laux
Affiliation:
Department of Pediatric Cardiology, Centre de Référence «Malformations cardiaques Congénitales Complexes-M3C»
Valérie Malan
Affiliation:
Department of Cytogenetics, Hôpital Necker-Enfants-Malades, Université Paris Descartes, Paris, France
Fanny Bajolle
Affiliation:
Department of Pediatric Cardiology, Centre de Référence «Malformations cardiaques Congénitales Complexes-M3C»
Younes Boudjemline
Affiliation:
Department of Pediatric Cardiology, Centre de Référence «Malformations cardiaques Congénitales Complexes-M3C»
Jeanne Amiel
Affiliation:
Department of Clinical Genetics, Hôpital Necker-Enfants-Malades, Université Paris Descartes, Paris, France
Damien Bonnet*
Affiliation:
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: damien.bonnet@nck.aphp.fr
Get access Rights & Permissions [Opens in a new window]

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.

Methods

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.

Results

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.

Discussion

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.

Keywords

Misalignment of pulmonary veinsneonatal pulmonary hypertensionpulmonary vascular diseasecardiac malformation16q24.1 microdeletion
Type
Original Articles
Information
Cardiology in the Young , Volume 23 , Issue 5 , October 2013 , pp. 697 - 704
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Janney, CG, Askin, FB, Kuhn, C III. Congenital alveolar capillary dysplasia – an unusual cause of respiratory distress in the newborn. Am J Clin Pathol 1981; 76: 722–727.Google Scholar
2. Wagenvoort, CA. Misalignment of lung vessels: a syndrome causing persistent neonatal pulmonary hypertension. Human Pathol 1986; 17: 727–730.Google Scholar
3. Rutledge, JC, Jensen, P. Acinar dysplasia: a new form of pulmonary maldevelopment. Hum Pathol 1986; 17: 1290–1293.Google Scholar
4. Langston, C. Misalignment of pulmonary veins and alveolar capillary dysplasia. Pediatr Pathol 1991; 11: 163–170.CrossRefGoogle ScholarPubMed
5. Abdallah, HI, Karmazin, N, Marks, LA. Late presentation of misalignment of lung vessels with alveolar capillary dysplasia. Crit Care Med 1993; 21: 628–630.Google Scholar
6. Garola, RE, Thibeault, DW. Alveolar capillary dysplasia, with and without misalignment of pulmonary veins: an association of congenital anomalies. Am J Perinatol 1998; 15: 103–107.Google Scholar
7. Lane, JR, Siwik, E, Preminger, T, Stork, E, Spector, M. Prospective diagnosis of alveolar capillary dysplasia in infants with congenital heart disease. Am J Cardiol 1999; 84: 618–620.Google Scholar
8. Rabah, R, Poulik, JM. Congenital alveolar capillary dysplasia with misalignment of pulmonary veins associated with hypoplastic left heart syndrome. Pediatr Dev Pathol 2001; 4: 167–174.Google Scholar
9. McGaughran, J, Souter, DJ, Kuschel, CA. Alveolar capillary dysplasia with antenatal anomalies mimicking trisomy 21. J Paediatr Child Health 2001; 37: 85–86.Google Scholar
10. Sen, P, Thakur, N, Stockton, DW, Langston, C, Bejjani, BA. Expanding the phenotype of alveolar capillary dysplasia (ACD). J Pediatr 2004; 145: 646–651.Google Scholar
11. Shehata, BM, Abramowsky, CR. Alveolar capillary dysplasia in an infant with trisomy 21. Pediatr Dev Pathol 2005; 8: 696–700.Google Scholar
12. Wright, GE, Nowak, CA, Goldberg, CS, Ohye, RG, Bove, EL, Rocchini, AP. Extended resection and end-to-end anastomosis for aortic coarctation in infants: results of a tailored surgical approach. Ann Thorac Surg 2005; 80: 1453–1459.Google Scholar
13. Roth, W, Bucsenez, D, Bläker, H, Berger, I, Schnabel, PA. Misalignment of pulmonary vessels with alveolar capillary dysplasia: association with atrioventricular septal defect and quadricuspid pulmonary valve. Virchows Arch 2006; 448: 375–378.Google Scholar
14. Taborosi, B, Tödt-Pingel, I, Kayser, G, Dittrich, S. A rare case of aortic coarctation and ventricular septal defect combined with alveolar capillary dysplasia. Pediatr Cardiol 2007; 28: 319–323.Google Scholar
15. Pasutto, F, Sticht, H, Hammersen, G, 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: 550–560.Google Scholar
16. Gamillscheg, A, Zobel, G, Spuller, E, Reiterer, F, Beitzke, A. Aortic coarctation associated with alveolar capillary dysplasia and misalignment of pulmonary veins. Pediatr Cardiol 2008; 29: 191–194.Google Scholar
17. Stankiewicz, P, Sen, P, Bhatt, SS, 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: 780–791.Google Scholar
18. Yu, S, Shao, L, Kilbride, H, Zwick, DL. Haploinsufficiencies of FOXF1 and FOXC2 genes associated with lethal alveolar capillary dysplasia and congenital heart disease. Am J Med Genet Part A 2010; 152A: 1257–1262.Google Scholar
19. Zufferey, F, Martinet, D, Osterheld, MC, 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: e427–e432.Google Scholar
20. Ahmed, S, Ackerman, V, Faught, P, Langston, C. Profound hypoxemia and pulmonary hypertension in a 7-month-old infant: late presentation of alveolar capillary dysplasia. Pediatr Crit Care Med 2008; 9: e43–e46.Google Scholar
21. Eulmesekian, P, Cutz, E, Parvez, B, Bohn, D, Adatia, I. Alveolar capillary dysplasia: a six-year single center experience. J Perinat Med 2005; 33: 347–352.Google Scholar
22. Inwald, D, Brown, K, Gensini, F, Malone, M, Goldman, A. Open lung biopsy in neonatal and paediatric patients referred for extracorporeal membrane oxygenation (ECMO). Thorax 2004; 59: 328–333.Google Scholar
23. Mahlapuu, M, Enerbäck, S, Carlsson, P. Haploinsufficiency of the forkhead gene Foxf1, a target for sonic hedgehog signaling, causes lung and foregut malformations. Development 2001; 128: 2397–2406.Google Scholar
Supplementary material: File

Laux Supplementary Material

Table S1

Download Laux Supplementary Material(File)
File 30.2 KB