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The Molecular Genetics of Conotruncal Defects

  • Chapter
Molecular Genetics of Cardiac Electrophysiology

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 231))

  • 109 Accesses

Abstract

Although conotruncal defects account for approximately 16% of all types of congenital heart disease (1), little is known about the molecular genetics of these malformations. Epidemiologic studies, naturally occurring animal models and animal experimentation support a genetic contribution to this class of disorders. However, identification of specific genetic etiologies has been difficult to accomplish for several reasons. First, unlike many of the disorders discussed previously in this textbook, most probands with severe conotruncal defects have not historically survived to reproduce so that families with many affected members do not exist. Most cases of conotruncal defects appear to be sporadic rather than familial. Therefore, investigators have not been able to perform linkage analyses to identify chromosomal disease loci or genes. Second, until more recently, very little was known of the developmental pathways and specific proteins involved in conotruncal and cardiac development so that candidate genes for human disease could not be proposed. Third, most probands with a conotruncal defect have normal standard karyotypes, so clues as to where disease genes might map are also uncommon. Nonetheless, significant progress has been made recently and more discoveries are likely to be made through the analysis of genetic syndromes in which congenital heart disease is a major feature. Moreover, a multitude of genes that contribute to conotruncal development are now being identified in mammalian models. These genes begin to unravel the developmental pathways that contribute to outflow tract formation and may turn out to be disease-related in some cases. Though much work remains to be done, the prospects of understanding specific genetic etiologies of these malformations are increasing.

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Authors and Affiliations

  1. Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Elizabeth Goldmuntz M.D.

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  1. Elizabeth Goldmuntz M.D.
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Editors and Affiliations

  1. Department of Cardiology, Children’s Hospital, Boston, USA

    Charles I. Berul M.D.

  2. Department of Pediatrics, Harvard Medical School, Boston, 02115, MA, USA

    Charles I. Berul M.D.

  3. Departments of Pediatrics (Cardiology), Molecular and Human Genetics, Texas Children’s Hospital, Baylor College of Medicine, Houston, 77030, TX, USA

    Jeffrey A. Towbin M.D.

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Goldmuntz, E. (2000). The Molecular Genetics of Conotruncal Defects. In: Berul, C.I., Towbin, J.A. (eds) Molecular Genetics of Cardiac Electrophysiology. Developments in Cardiovascular Medicine, vol 231. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4517-0_22

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  • DOI: https://doi.org/10.1007/978-1-4615-4517-0_22

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