Tetralogy of fallot and hypoplastic left heart syndrome – complex clinical phenotypes meet complex genetic networks

Harald Lahm, Patric Schön, Stefanie Doppler, Martina Dreßen, Julie Cleuziou, Marcus André Deutsch, Peter Ewert, Rüdiger Lange, Markus Krane

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


In many cases congenital heart disease (CHD) is represented by a complex phenotype and an array of several functional and morphological cardiac disorders. These malformations will be briefly summarized in the first part focusing on two severe CHD phenotypes, hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot (TOF). In most cases of CHD the genetic origin remains largely unknown, though the complexity of the clinical picture strongly argues against a dysregulation which can be attributed to a single candidate gene but rather suggests a multifaceted polygenetic origin with elaborate interactions. Consistent with this idea, genome-wide approaches using whole exome sequencing, comparative sequence analysis of multiplex families to identify de novo mutations and global technologies to identify single nucleotide polymorphisms, copy number variants, dysregulation of the transcriptome and epigenetic variations have been conducted to obtain information about genetic alterations and potential predispositions possibly linked to the occurrence of a CHD phenotype. In the second part of this review we will summarize and discuss the available literature on identified genetic alterations linked to TOF and HLHS.

Original languageEnglish
Pages (from-to)141-158
Number of pages18
JournalCurrent Genomics
Issue number3
StatePublished - 1 Jan 2015


  • Congenital heart disease
  • Copy number variants
  • De novo mutations
  • Epigenetics
  • Genome-wide association study
  • Hypoplastic left heart syndrome
  • Tetralogy of fallot


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