Structural heart disease

Catherine L. Mercer; David I. Wilson

doi:10.1017/CBO9780511997778.013

Chapter 9.2 - Structural heart disease

Genetic influences

from Section 2 - Fetal disease

Published online by Cambridge University Press: 05 February 2013

Catherine L. Mercer and

Edited by

Anthony Johnson and

Mark D. Kilby: Affiliation:
Department of Fetal Medicine, University of Birmingham
Anthony Johnson: Affiliation:
Baylor College of Medicine, Texas
Dick Oepkes: Affiliation:
Department of Obstetrics, Leiden University Medical Center

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Summary

Introduction

Our understanding about the genetic influences on human disease has increased dramatically with the technological developments in genome and DNA analysis and the discovery of the human genome sequence. Whilst much remains unexplained, it is obvious that normal cardiac development is controlled by the genome and there is significant evidence that a proportion of cardiac malformations are caused by genetic factors. This is important for clinicians as an understanding of confirmed genetic factors is essential to estimate recurrence risks of congenital heart disease (CHD) within families and also screen for predicted associated anomalies. An accurate genetic diagnosis can provide important prognostic information for both the initial patient (proband) and other family members, for whom further genetic investigations may be indicated. There is likely to be increased demand for such investigations as improvement in surgical and medical management allows more individuals with CHD to survive to reproductive age and have families of their own. For some the recurrence risk for a cardiac malformation may be as high as 50%; the actual figure varies with different genetic diagnoses. Accurate risk stratification is likely to become increasingly important, and the rapidly developing technologies to detect genetic variation will mean genome-wide investigation will become available in a clinical setting. An aim of this chapter is to introduce clinicians to principles that will help them embrace and understand the results from these investigations and appreciate the implications they will have for their patients.

Birth incidence of congenital heart disease

CHD is one of the commonest human birth defects, with a widely reported birth incidence of just less than 1% [1], and it accounts for one-third of infant deaths that result from congenital malformation. If a broader criteria for CHD is taken that includes any malformation rather than just those with clinical significance (e.g., very small muscular ventricular septal defects [VSDs] or bicuspid aortic valves) the incidence is higher; bicuspid aortic valve is found in ~1–2% of neonates [2]. The incidence of CHD severe enough to require specialized management has remained relatively constant however [3], at around 3/1000 [4].

Keywords

structural heart disease gene mapping genetic factors genome sequencing DNA sequence birth defects chromosomal aneuploidy

Type: Chapter
Information: Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
, pp. 113 - 122

DOI: https://doi.org/10.1017/CBO9780511997778.013 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2012

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Chapter 9.2 - Structural heart disease

Summary

Keywords

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