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Chapter 9.2 - Structural heart disease

Genetic influences

from Section 2 - Fetal disease

Published online by Cambridge University Press:  05 February 2013

By
Catherine L. Mercer  and
David I. Wilson
Edited by
Mark D. Kilby ,
Anthony Johnson  and
Dick Oepkes
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 diseasegene mappinggenetic factorsgenome sequencingDNA sequencebirth defectschromosomal aneuploidy
Type
Chapter
Information
Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
 , pp. 113 - 122
Publisher: Cambridge University Press
Print publication year: 2012

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