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.

Familial recurrence of congenital heart disease: an overview and review of the literature

“…TGA itself was the most common recurrent malformation, suggesting monogenic or oligogenic inheritance. In addition, we recently conducted a familial study regarding patients with congenitally corrected TGA (CCTGA) [35]. In these cases, the risk of recurrence was 5.2%, higher than the classic 3% considered for the multifactorial risk of recurrence.…”

“…It must be considered that in the pathogenetic classification of CHDs, CCTGA is included among laterality defects, and the recurrence risk we found in our series is similar to the higher risk proposed for situs and looping anomalies. Interestingly, several pedigrees showed familial segregation of both complete TGA and CCTGA in sibs [10,35]. This finding indicates a pathogenetic link between some cases of complete TGA and the situs and looping abnormalities.…”

Congenitally Corrected Transposition of the Great Arteries

“…The incidence of ccTGA in patients with congenital heart disease (CHD) is approximately 0.5% with a slight male predominance (Graham & Markham, 2010;Piacentini et al, 2005). Although a specific genetic defect is yet to be defined for ccTGA, the recurrence risk of dwww.intechopen.com TGA for siblings of ccTGA patients is 2.6% with an overall recurrence risk of 5.2% for ccTGA siblings to have some type of congenital heart defect (Piacentini et al, 2005).…”

“…Although a specific genetic defect is yet to be defined for ccTGA, the recurrence risk of dwww.intechopen.com TGA for siblings of ccTGA patients is 2.6% with an overall recurrence risk of 5.2% for ccTGA siblings to have some type of congenital heart defect (Piacentini et al, 2005). A recurrence risk of >5% is higher than expected, as the risk is typically thought to be 1-3% for unaffected parents to have an additional child with congenital heart disease ( Van der Bom et al, 2011).…”

Cardiac Conduction System in Congenitally Corrected Transposition of the Great Arteries and Its Clinical Relevance

“…The incidence has been reported to be around 1/33 000 live births, accounting for ≈0.05% of congenital heart malformations 2. Although a familial recurrence of heart defects in subjects with ccTGA has been reported,3 the etiology of this malformation is not currently known 1, 4…”