Genetic cause identified in fewer than half of congenital heart disease casesGenetic causes identified in fewer than half of heart cases

This narrative review addresses the genetic underpinnings of congenital heart diseases (CHD), the most common birth defects. The authors synthesize current knowledge on how genetic variants disrupt heart development, offering a framework that links molecular findings to developmental biology. They emphasize that despite advances, a definitive or candidate genetic cause is identified in fewer than half of cases, highlighting the complexity and heterogeneity of CHD genetics.

The review is intended to help clinicians situate molecular findings within the biology of heart formation, sharpen genotype–phenotype interpretation, and support more precise diagnostic and prognostic reasoning. It also touches on emerging regenerative strategies, though these are discussed in a conceptual rather than clinical context.

As a narrative review, it does not present pooled data or systematic methodology. The authors do not report specific trial data, and the review does not provide evidence of treatment efficacy. Limitations are not explicitly stated in the source, but the lack of quantitative synthesis and reliance on selected literature are inherent constraints.

For clinicians, the review offers a conceptual map for integrating genetic testing into CHD care, but it should not be used as a basis for specific treatment decisions. The finding that most cases remain genetically unexplained underscores the need for cautious interpretation of negative genetic results.