Abstract Title:

Consanguinity and Atrial Septal Defect: Genetic and Environmental Factors in Global Populations

Background:

Atrial septal defect (ASD) accounts for approximately 10 to 15 percent of congenital heart diseases, with a reported birth prevalence of approximately 1 to 2 per 1000 live births. This study aims to explore the relationship between consanguinity and ASD, addressing gaps in understanding both genetic and environmental factors.

Methods:

A search of PubMed articles (January 1950 - July 2024) using Medical Subject Headings (MeSH) terms 'congenital heart disease' and 'consanguinity', limited to English language articles, yielded 642 results. The focus was on articles that studied the relationship between consanguinity and ASD across various countries.

Results:

A Moroccan study found 3 heterozygous NKX2-5 variants in 9.4% of ASD patients, with 30.8% reporting consanguinity. In Northeast Iran, 85% of ASD patients had secundum ASD, and consanguinity significantly correlated with ASD type (P < 0.001), gender (P < 0.001), and age of onset (P = 0.003). Western Iraq exhibited notably higher consanguinity rates in congenital heart disease cases (78%) compared to controls (43.3%), with first-cousin consanguinity particularly elevated in cases (66.2%) versus controls (35.6%). In South India, consanguinity, including first cousin (44.68%) and uncle-niece marriages (46.81%), significantly increased the risk of ASD.

Conclusion:

These findings underscore a significant relationship between consanguinity and ASD prevalence, with consanguinity emerging as a substantial environmental risk factor alongside genetic predispositions such as NKX2-5 variants. The Moroccan cohort study suggests that consanguinity, coupled with a high incidence of maternal miscarriages and sudden sibling deaths, indicates a non-sporadic nature of ASD, potentially influenced by ethnicity. Studies in Western Iraq and South India show that consanguinity significantly increases the risk of ASD, highlighting the role of recessive gene segregation. The elevated prevalence of ASD among consanguineous marriages emphasizes the need for pre-marriage counseling to educate couples about the genetic risks associated with inbreeding. Social education campaigns could raise awareness about these risks and promote healthy family planning practices. Understanding the interplay between genetic and environmental factors is crucial for developing effective prevention and management strategies. Future research should prioritize whole-exome sequencing to identify causative genes of ASD within consanguineous communities.