© 1997 American Heart Association, Inc.
Articles |
Genetic Disorders of Cardiac Morphogenesis
The DiGeorge and Velocardiofacial Syndromes
From the Division of Human Genetics and Molecular Biology (B.S.E.) and the Division of Cardiology (E.G.), the Department of Pediatrics, University of Pennsylvania, Philadelphia.
Correspondence to Dr Elizabeth Goldmuntz, Division of Cardiology, The Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104.
Key Words: DiGeorge syndrome • velocardiofacial syndrome • chromosome 22 • microdeletion syndrome • conotruncal defects
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Introduction |
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Congenital heart defects are thought to result from a variety of genetic and environmental influences. Although most CHD occurs as a sporadic event, many defects are part of a well-defined genetic syndrome. Particular types of CHD are often overrepresented in the context of a syndrome compared with the general population. Identification of the genetic etiology of the syndrome may lend insight into the etiology of the associated cardiac malformation. Thus, because conotruncal cardiac defects are a cardinal feature of DGS, the specific genetic etiology of this syndrome has become of great interest to the cardiologist and cardiac developmental biologist.
Although the phenotype is highly variable, DGS is typically characterized by aplasia or hypoplasia of the thymus, aplasia or hypoplasia of the parathyroid glands, conotruncal cardiac defects, and mildly dysmorphic facial features.1 2 The most common cardiac defects include truncus arteriosus, interrupted aortic arch, and tetralogy of Fallot.3 Defects in multiple organ systems, which arise concurrently and from common precursors during embryogenesis, have led to the proposal that DGS is a developmental field defect.4 A developmental field refers to a population of embryonic cells that behave as a single coordinated developmental unit. Disruption of this "morphogenetically reactive unit" results in a particular phenotype, which may involve many different end organs and may be phenotypically variable depending upon the timing and nature of the perturbation. Different factors, such as genetic alterations or environmental insults, could disrupt the normal morphogenesis of the reactive unit and result in a similar phenotype.
Preliminary evidence suggests that
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