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(Circulation. 2001;104:2809.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Complete Transposition of the Great Arteries

Patterns of Congenital Heart Disease in Familial Precurrence

Maria Cristina Digilio, MD; Brett Casey, MD; Alessandra Toscano, MD; Raffaele Calabrò, MD; Giuseppe Pacileo, MD; Maurizio Marasini, MD; Elena Banaudi, MD; Aldo Giannotti, MD; Bruno Dallapiccola, MD; Bruno Marino, MD

From the Departments of Medical Genetics and Pediatric Cardiology, Bambino Gesù Hospital, Rome (M.C.D., A.T., A.G.); the Department of Pathology, Baylor College of Medicine and Texas Children’s Hospital, Houston (B.C.); the Department of Pediatric Cardiology, Monaldi Hospital, Napoli, Italy (R.C., G.P.); the Department of Pediatric Cardiology, G. Gaslini Hospital, Genova, Italy (M.M.); the Department of Pediatric Cardiology, Regina Margherita Hospital, Torino, Italy (E.B.); the Department of Medical Genetics, La Sapienza University and Mendel-CSS Institute, Rome, Italy (B.D.); and the Division of Pediatric Cardiology, Department of Pediatrics, La Sapienza University, Rome, Italy (B.M.).

Correspondence to B. Marino, Cardiologia Pediatrica, Istituto di Pediatria, Università La Sapienza, Viale Regina Elena 324, 00161, Roma, Italia. E-mail bruno.marino{at}uniroma1.it

Background— Transposition of the great arteries (TGA) is considered to be associated only rarely with genetic syndromes and to have a low risk of precurrence among relatives of affected patients. Because most family studies have involved a relatively small number of patients and evaluated all types of TGA as a single group, we performed a large, prospective study investigating the precurrence of congenital heart disease in families of children with complete, nonsyndromic TGA.

Methods and Results— From January 1997 through December 2000, 370 patients with nonsyndromic, complete TGA were consecutively evaluated and enrolled in the study. The occurrence of cardiac and noncardiac anomalies among relatives of the probands was investigated. Relatives with congenital heart disease were found in 37 of 370 families (10%), including 5 of 37 families (13.5%) with more than one affected relative. TGA itself was the most common precurrent malformation: complete TGA occurred in 6 families and congenitally corrected TGA occurred in 5 families. Precurrence risks for congenital heart disease were calculated at 1.8% (8 of 436) for siblings, 0.5% (4 of 740) for parents, 0.5% (16 of 3261) for first cousins, 0.2% (4 of 2101) for uncles/aunts, and 0.06% (1 of 1480) for grandparents.

Conclusions— The present study shows that TGA is not always sporadic in families. Precurrence of concordant cardiac defects within affected family members supports monogenic or oligogenic inheritance of TGA in certain kindreds. Moreover, the occurrence of complete TGA and congenitally corrected TGA among first-degree relatives in several different families strongly suggests an underlying pathogenetic link between these 2 malformations that has been previously unrecognized.

Key Words: heart defects, congenital • transposition of great vessels • genetics

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