Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study
Marine Tortigue, Lynne E. Nield, Matilde Karakachoff, Christopher J. McLeod, Emré Belli, Sonya V. Babu‐Narayan, Solène Prigent, Angèle Boët, Miriam Conway, Robert W. Elder, Magalie Ladouceur, Paul Khairy, Ewa Kowalik, David Kalfa, David J. Barron, Shafi Mussa, Anita Hiippala, Joel Temple, Sylvia Abadir, Laurianne Le Gloan, Matthias Lachaud, Shubhayan Sanatani, Jean‐Benoît Thambo, Céline Gronier, Pascal Amédro, 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 Α. Gatzoulis, Dominic J. Abrams, Anne M. Dubin, Siew Yen Ho, Richard Redon, Emile Bacha, Jean‐Jacques Schott, Alban‐Elouen Baruteau
Abstract
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.