Genetic detection of congenital heart disease

Sumathi I. Rachamadugu, Kristen A. Miller, Ina H. Lee, Ying S. Zou

Research output: Contribution to journalReview articlepeer-review


Congenital heart disease (CHD) is the most common congenital anomaly and is an important cause of infant morbidity and mortality. Besides the epigenetic and environmental basis of CHD, genetics plays a central role in CHD pathogenesis. Traditional genetic testing strategies including conventional chromosome analysis, fluorescence in situ hybridization, and Sanger sequencing have largely focused on syndromic CHD or selected CHD phenotypes that are strongly associated with a particular genotype. The landscape of clinical genetic testing in CHD is rapidly evolving due to technical advances in genetic testing, including the identification of copy number variants by chromosomal microarray and nucleotide level alterations/variants by next-generation sequencing (NGS), which are essential to detect genetic causes of CHD and identify associations between genotypes and longitudinal clinical phenotypes. Whole-exome and whole-genome NGS not only reveal pathogenic variants in CHD genes, but also identify non-coding variants that influence the expression of CHD genes. Given the increasing availability and cost-effectiveness of clinical NGS to provide information on the causes of CHD and to detect incidental findings that are clinically actionable, the guidance of genetic counselors or experienced clinicians is essential. The identification of definitive causal CHD variants influences patient care and helps to inform the risk of recurrence, prenatal genetic counseling, and pre-implantation testing for the family of a CHD infant and adults with repaired/palliated CHD. Prenatally, circulating cell-free DNA screening as a non-invasive approach is available as early as 9 weeks of gestation and can screen for the common aneuploidies, which may underlie CHD. In this review, we present past and recent genetic testing in CHD based on our increased understanding of the pathogenesis of CHD along with current challenges with the interpretation of de novo genetic variants. Identification of a genetic diagnosis can help to predict and potentially improve clinical outcomes in CHD patients.

Original languageEnglish (US)
Pages (from-to)109-123
Number of pages15
JournalGynecology and Obstetrics Clinical Medicine
Issue number3
StatePublished - Sep 2022


  • Circulating cell-free DNA Screening
  • Congenital heart disease
  • Gene variant
  • Next generation sequencing
  • Whole-genome sequencing

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology


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