Double outlet right ventricle: aetiologies and associations

Area of Science:

• Cardiology
• Genetics
• Developmental Biology

Background:

• Double outlet right ventricle (DORV) is a significant congenital heart defect affecting 1-3% of affected individuals.
• Limited systematic data exist on DORV associations, etiologies, and pathogenesis.
• This study addresses these knowledge gaps by analyzing reported DORV cases.

Purpose of the Study:

• To comprehensively review and analyze existing literature on double outlet right ventricle (DORV).
• To identify and categorize the associations, etiologies, and pathogenetic mechanisms of DORV.
• To explore genetic and environmental factors implicated in DORV development.

Main Methods:

• Systematic literature search of PubMed using keywords "double outlet right ventricle" and "DORV".
• Inclusion of case reports, epidemiologic analyses, and animal studies.
• Classification of DORV anatomic subtypes according to Van Praagh criteria.

Main Results:

• Chromosomal abnormalities were found in 61 of 149 DORV cases, with Trisomies 13 and 18, and del 22q11 being most common.
• Distinct anatomic subtypes of DORV were observed in relation to specific chromosomal abnormalities.
• Monogenic loci, including CFC1 and CSX genes, and numerous genes in murine models were associated with DORV; environmental factors like maternal diabetes and prenatal exposures were implicated.

Conclusions:

• The multitude of associated genes in humans and animal models suggests multiple distinct pathogenetic mechanisms for DORV.
• Impaired neural crest cell migration and abnormal cardiac looping/situs are likely key mechanisms.
• Understanding these diverse etiologies is crucial for DORV research and clinical management.