Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study. (12th May 2022)

• Record Type: Journal Article
• Authors: Tortigue, Marine; Nield, Lynne E.; Karakachoff, Matilde; McLeod, Christopher J.; Belli, Emre; Babu-Narayan, Sonya V.; Prigent, Solène; Boet, Angèle; Conway, Miriam; Elder, Robert W.; Ladouceur, Magalie; Khairy, Paul; Kowalik, Ewa; Kalfa, David M.; Barron, David J.; Mussa, Shafi; Hiippala, Anita; Temple, Joel; Abadir, Sylvia; Le Gloan, Laurianne; Lachaud, Matthias; Sanatani, Shubhayan; Thambo, Jean-Benoit; Gronier, Céline Grunenwald; Amedro, Pascal; Vaksmann, Guy; Charbonneau, Anne; Koutbi, Linda; Ovaert, Caroline; Houeijeh, Ali; Combes, Nicolas; Maury, Philippe; Duthoit, Guillaume; Hiel, Bérengère; Erickson, Christopher C.; Bonnet, Caroline; Van Hare, George F.; Dina, Christian; Karsenty, Clément; Fournier, Emmanuelle; Le Bloa, Mathieu; Pass, Robert H.; Liberman, Leonardo; Happonen, Juha-Matti; Perry, James C.; Romefort, Bénédicte; Benbrik, Nadir; Hauet, Quentin; Fraisse, Alain; Gatzoulis, Michael A.; Abrams, Dominic J.; Dubin, Anne M.; Ho, Siew Yen; Redon, Richard; Bacha, Emile A.; Schott, Jean-Jacques; Baruteau, Alban-Elouen;
• Is Part Of: Circulation. Volume 15:Number 3(2022)
• Page Start: e003464
• Publication Date: 2022-05-12
• Subjects: aorta -- arteries -- heterotaxy syndrome -- mitral valve -- rare disease; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Genetics -- Periodicals; Cardiovascular Diseases -- genetics; Precision Medicine; Periodical; Fulltext; Internet Resources; Periodicals; Electronic journals; Periodicals; 616.1042
• DOI: 10.1161/CIRCGEN.121.003464
• Languages: English
• ISSNs: 2574-8300

Abstract

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.