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Review
. 2018 Sep;10(Suppl 24):S2848-S2853.
doi: 10.21037/jtd.2018.02.53.

Electrical disorders in atrial septal defect: genetics and heritability

Hisaaki Aoki  1 , Minoru Horie  2
Affiliations
Review

Electrical disorders in atrial septal defect: genetics and heritability

Hisaaki Aoki et al. J Thorac Dis. 2018 Sep.

Abstract

Atrial septal defect (ASD) is one of the most common types of congenital heart diseases (CHDs). Most ASDs occur sporadically, but some are inherited and associated with cardiac conduction defects such as atrioventricular block (AVB) or bundle branch block. Mutations in genes encoding transcription factor gene TBX5 and NKX2-5, were found in Holt-Oram syndrome (HOS) and ASD with atrioventricular (AV) conduction defects, respectively. HOS is characterized by upper limb anomaly in addition to ASD and AVB (heart-hand syndrome). ASD associated with NKX2-5 is rare but is reported to cause sudden cardiac death (SCD) or cardiomyopathy. We provide a review of these two diseases.

Keywords: Atrial septal defect (ASD); Holt-Oram syndrome (HOS); NKX2-5; TBX5; atrioventricular block (AVB); genetics.

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Molecular pathways regulating the development of the fast-conducting bundle of His and its tributaries. TBX2 and TBX3 suppress the expression of chamber myocardium genes: ANF, GJA5 (Cx40), and GJA1 (Cx43), which differentiate toward rapid conduction, along with muscle-segment homeobox transcription factor MSX1 and MSX2. While TBX5 and NKX2-5 activate the expression of ANF and Cx40. Together with TBX5, GATA4 activates Cx30.2 expression, which is detected in AVN and retains the slow conduction [cited from reference (6)]. AVN, atrioventricular node.
Figure 2
Figure 2
ECG findings in Holt-Oram syndrome. The electrocardiography exhibited PR prolongation and left bundle branch block.
See this image and copyright information in PMC

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