Congenital heart disease and genetic syndromes: new insights into molecular mechanisms

Expert Rev Mol Diagn. 2017 Sep;17(9):861-870. doi: 10.1080/14737159.2017.1360766. Epub 2017 Aug 3.


Advances in genetics allowed a better definition of the role of specific genetic background in the etiology of syndromic congenital heart defects (CHDs). The identification of a number of disease genes responsible for different syndromes have led to the identification of several transcriptional regulators and signaling transducers and modulators that are critical for heart morphogenesis. Understanding the genetic background of syndromic CHDs allowed a better characterization of the genetic basis of non-syndromic CHDs. In this sense, the well-known association of typical CHDs in Down syndrome, 22q11.2 microdeletion and Noonan syndrome represent paradigms as chromosomal aneuploidy, chromosomal microdeletion and intragenic mutation, respectively. Area covered: For each syndrome the anatomical features, distinctive cardiac phenotype and molecular mechanisms are discussed. Moreover, the authors include recent genetic findings that may shed light on some aspects of still unclear molecular mechanisms of these syndromes. Expert commentary: Further investigations are needed to enhance the translational approach in the field of genetics of CHDs. When there is a well-established definition of genotype-phenotype (reverse medicine) and genotype-prognosis (predictive and personalized medicine) correlations, hopefully preventive medicine will make its way in this field. Subsequently a reduction will be achieved in the morbidity and mortality of children with CHDs.

Keywords: 22q11.2DS; Congenital heart defects; DiGeorge syndrome; Down syndrome; Noonan syndrome; RASopathy syndrome; trisomy 21.

Publication types

  • Review

MeSH terms

  • Chromosome Aberrations
  • Genetic Association Studies* / methods
  • Genetic Markers
  • Genotype
  • Heart Defects, Congenital / diagnosis*
  • Heart Defects, Congenital / epidemiology
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / therapy
  • Humans
  • Mutation
  • Phenotype
  • Syndrome


  • Genetic Markers