A Path to Implement Precision Child Health Cardiovascular Medicine

Area of Science:

• Cardiovascular Medicine
• Genetics
• Developmental Biology

Background:

• Congenital heart defects (CHDs) affect ~1% of live births, causing significant childhood morbidity and mortality.
• The etiology of CHDs is multifactorial, involving genetic, epigenetic, and environmental factors, yet many cases lack clear diagnosis and targeted therapies.
• Improving diagnostic precision and developing targeted therapies are critical for optimizing quality of life and minimizing complications in CHD patients.

Purpose of the Study:

• To outline a systematic, multileveled approach for dissecting the mechanisms underlying CHDs.
• To emphasize the need for integrating clinical phenotyping with molecular analyses for precise diagnosis.
• To highlight the importance of establishing a CHD BioCore for advancing precision cardiovascular medicine in children.

Main Methods:

• Systematic multileveled approach from clinical phenotypic characterization to molecular dissection.
• Utilizing combined next-generation sequencing platforms (whole-exome sequencing, transcriptome analysis).
• Integration of phenotypic, genotypic, and molecular datasets to identify disease-associated networks.
• Generation of relevant disease models for experimental validation.

Main Results:

• The majority of CHDs lack clear diagnosis of underlying genetic and environmental factors, hindering targeted therapy development.
• Identification of disease-associated genetic variants is challenging, impeding understanding of gene-environment interactions in CHD pathogenesis.
• A systematic approach is proposed to bridge clinical observation with molecular investigation.

Conclusions:

• A systematic, multileveled strategy is essential for advancing the understanding and treatment of CHDs.
• Establishing a CHD BioCore with high-quality biological specimens from well-defined cohorts is critical.
• This infrastructure will facilitate precision child health cardiovascular medicine by enabling precise diagnosis and targeted therapies.