Electrical disorders in atrial septal defect: genetics and heritability

Area of Science:

• Cardiology
• Genetics
• Developmental Biology

Background:

• Atrial septal defect (ASD) is a frequent congenital heart disease (CHD).
• Some ASD cases are inherited, often linked to cardiac conduction defects like atrioventricular block (AVB).
• Genetic factors play a role in specific ASD presentations and associated anomalies.

Purpose of the Study:

• To review inherited forms of ASD.
• To discuss the genetic basis of ASD associated with specific cardiac conduction defects.
• To highlight Holt-Oram syndrome (HOS) and NKX2-5 related ASD.

Main Methods:

• Literature review of genetic mutations and associated clinical phenotypes.
• Analysis of studies on TBX5 and NKX2-5 gene mutations in ASD.
• Synthesis of information on HOS and ASD with AV conduction defects.

Main Results:

• Mutations in TBX5 gene are associated with Holt-Oram syndrome (ASD, upper limb anomaly, AVB).
• Mutations in NKX2-5 gene are linked to ASD with atrioventricular conduction defects, potentially causing sudden cardiac death or cardiomyopathy.
• These genetic links underscore the role of specific genes in CHD development.

Conclusions:

• TBX5 and NKX2-5 gene mutations are critical in specific inherited forms of ASD.
• Understanding these genetic underpinnings is crucial for diagnosing and managing these congenital heart conditions.
• Further research into genetic factors can improve outcomes for patients with CHD.