TY - JOUR
T1 - Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries
T2 - An International Study
AU - Tortigue, Marine
AU - Nield, Lynne E.
AU - Karakachoff, Matilde
AU - McLeod, Christopher J.
AU - Belli, Emre
AU - Babu-Narayan, Sonya V.
AU - Prigent, Solène
AU - Boet, Angèle
AU - Conway, Miriam
AU - Elder, Robert W.
AU - Ladouceur, Magalie
AU - Khairy, Paul
AU - Kowalik, Ewa
AU - Kalfa, David M.
AU - Barron, David J.
AU - Mussa, Shafi
AU - Hiippala, Anita
AU - Temple, Joel
AU - Abadir, Sylvia
AU - Le Gloan, Laurianne
AU - Lachaud, Matthias
AU - Sanatani, Shubhayan
AU - Thambo, Jean Benoit
AU - Gronier, Céline Grunenwald
AU - Amedro, Pascal
AU - Vaksmann, Guy
AU - Charbonneau, Anne
AU - Koutbi, Linda
AU - Ovaert, Caroline
AU - Houeijeh, Ali
AU - Combes, Nicolas
AU - Maury, Philippe
AU - Duthoit, Guillaume
AU - Hiel, Bérengère
AU - Erickson, Christopher C.
AU - Bonnet, Caroline
AU - Van Hare, George F.
AU - Dina, Christian
AU - Karsenty, Clément
AU - Fournier, Emmanuelle
AU - Le Bloa, Mathieu
AU - Pass, Robert H.
AU - Liberman, Leonardo
AU - Happonen, Juha Matti
AU - Perry, James C.
AU - Romefort, Bénédicte
AU - Benbrik, Nadir
AU - Hauet, Quentin
AU - Fraisse, Alain
AU - Gatzoulis, Michael A.
AU - Abrams, Dominic J.
AU - Dubin, Anne M.
AU - Ho, Siew Yen
AU - Redon, Richard
AU - Bacha, Emile A.
AU - Schott, Jean Jacques
AU - Baruteau, Alban Elouen
N1 - Funding Information:
By a grant from the Polish Ministry of Science and Higher Education (to Dr Kowalik); by a research grant from the Association for European Paediatric Cardiology (to Dr Baruteau), a research grant from the Lefoulon-Delalande Foundation (to Dr Baruteau) and a research grant from the European Heart Rhythm Association (to Dr Baruteau).
Funding Information:
We are grateful to Dr Sylvie Falcon-Eicher (CHU Dijon, France) for her kind help in data collection. We also gratefully acknowledge the Association for European Paediatric Cardiology, the Pediatric and Congenital Electrophysiology Society and the French Society of Cardiology for supporting this study. We also thank the European Reference Network on Rare and Complex Diseases of the Heart (ERN GUARD-HEART).
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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.
AB - 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.
KW - Aorta
KW - Arteries
KW - Heterotaxy syndrome
KW - Mitral valve
KW - Rare disease
UR - http://www.scopus.com/inward/record.url?scp=85132454609&partnerID=8YFLogxK
U2 - 10.1161/CIRCGEN.121.003464
DO - 10.1161/CIRCGEN.121.003464
M3 - Article
C2 - 35549293
AN - SCOPUS:85132454609
SN - 2574-8300
VL - 15
SP - E003464
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
IS - 3
ER -