title: Familial recurrence of heart defects in subjects with congenitally corrected transposition of the great arteries.
abstract: Familial recurrence of congenitally corrected transposition of the great arteries (CCTGA) is considered uncommon. Most of the previous familial studies involved a small number of patients and referred to all situs and looping anomalies including single ventricle, heterotaxia, and other cardiac defects different from CCTGA. We performed a large, consecutive clinical case series study in order to detect the recurrence of congenital heart defects in families of children with the classic form of CCTGA. From January 1997 through December 2004, 102 consecutive patients with CCTGA were evaluated in four institutions. There were 59 male (57.8%) and 43 female (42.2%). Mean age was 8.6 +/- 7.8 years. Eighty-eight patients (86.3%) had situs solitus of the atria, 14 (13.7%) situs inversus. The cardiac and extracardiac anomalies among relatives and the patterns of familial recurrence were investigated. Relatives with congenital heart defects were found in 16/102 families (15.7%). Transposition of the great arteries (TGA) was the most common recurrent defect (6/102 families). Consanguinity was identified in the parents of three probands. Six probands had an unaffected twin-sib. Recurrence risks for congenital heart defects were calculated at 5.2% (6/116) for siblings. In conclusion, CCTGA is not always sporadic in families. The pattern of inheritance, the presence of consanguinity among parents and the recurrence of situs inversus could suggest, in some families, an autosomal recessive mechanism with similarities with that occurring in some pedigrees with heterotaxia. The recurrence of TGA and CCTGA in the same family suggests a pathogenetic link between these two anatomically different malformations.
authors.affiliation: Department of Pediatrics and Genetics, University La Sapienza-Mendel Institute, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Piacentini
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Digilio
authors.forename: Rossella
authors.initials: R
authors.lastname: Capolino
authors.forename: Andrea De
authors.initials: AD
authors.lastname: Zorzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Toscano
authors.forename: Anna
authors.initials: A
authors.lastname: Sarkozy
authors.forename: Rita
authors.initials: R
authors.lastname: D'Agostino
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marasini
authors.forename: M Giovanna
authors.initials: MG
authors.lastname: Russo
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Bruno
authors.initials: B
authors.lastname: Marino
mesh_terms: D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D012307:Risk Factors; D014188:Transposition of Great Vessels / Q000235:genetics*