Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study

Marine Tortigue, Lynne E. Nield, Matilde Karakachoff, Christopher J. McLeod, Emre Belli, Sonya V. Babu-Narayan, Solène Prigent, Angèle Boet, Miriam Conway, Robert W. Elder, Magalie Ladouceur, Paul Khairy, Ewa Kowalik, David M. Kalfa, David J. Barron, Shafi Mussa, Anita Hiippala, Joel Temple, Sylvia Abadir, Laurianne Le GloanMatthias Lachaud, Shubhayan Sanatani, Jean Benoit Thambo, Céline Grunenwald Gronier, Pascal Amedro, Guy Vaksmann, Anne Charbonneau, Linda Koutbi, Caroline Ovaert, Ali Houeijeh, Nicolas Combes, Philippe Maury, Guillaume Duthoit, Bérengère Hiel, Christopher C. Erickson, Caroline Bonnet, George F. Van Hare, Christian Dina, Clément Karsenty, Emmanuelle Fournier, Mathieu Le Bloa, Robert H. Pass, Leonardo Liberman, Juha Matti Happonen, James C. Perry, Bénédicte Romefort, Nadir Benbrik, Quentin Hauet, Alain Fraisse, Michael A. Gatzoulis, Dominic J. Abrams, Anne M. Dubin, Siew Yen Ho, Richard Redon, Emile A. Bacha, Jean Jacques Schott, Alban Elouen Baruteau

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3 Scopus citations


Background: Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown cause. We aimed to better understand familial recurrence patterns. Methods: An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, entailing investigation of 1043 unrelated ccTGA probands. Results: Laterality defects and atrioventricular block at diagnosis were observed in 29.9% and 9.3%, respectively. ccTGA was associated with primary ciliary dyskinesia in 11 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-Transposition of the great arteries (28.4%), laterality defects (13.6%), and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and dextro-Transposition of the great arteries, and 9 familial co-segregation of ccTGA and laterality defects. In one family co-segregation of ccTGA, dextro-Transposition of the great arteries and heterotaxy syndrome in 3 distinct relatives was found. In another family, twins both displayed ccTGA and primary ciliary dyskinesia. Conclusions: ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, dextro-Transposition of the great arteries, laterality defects and in some cases primary ciliary dyskinesia, strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.

Original languageEnglish
Pages (from-to)E003464
JournalCirculation: Genomic and Precision Medicine
Issue number3
StatePublished - Jun 1 2022


  • Aorta
  • Arteries
  • Heterotaxy syndrome
  • Mitral valve
  • Rare disease


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