The Epidemiology and Genetics of Hypoplastic Left Heart Syndrome
Hypoplastic left heart syndrome (HLHS) is a common major congenital malformation, but very little is known about its etiology. Some hypothesize and animal models indicate that diminished blood flow through the left side of the fetal heart results in retarded growth and consequent hypoplasia of the left-sided structures (see Chapter 2 for further discussion). However, the primary mechanisms that cause this diminution of flow, whether they are structural or functional alterations, have not been defined and are likely to be heterogeneous. Epidemiologic studies point to a genetic component in the etiology of HLHS, as do reports of families with multiple affected members and its consistent association with specific genetic syndromes. These studies also demonstrate that, in some cases, HLHS is likely to represent a continuum of disease with other left-sided lesions of the heart including coarctation of the aorta and aortic valve stenosis. However, it has been particularly difficult to identify the genetic etiology of HLHS given the rarity of large families with multiple affected members for which a linkage analysis could be performed to identify a chromosomal disease locus. In addition, very few candidate genes from animal models have been identified that could be tested as disease-related in humans. In the following sections, the epidemiology of HLHS and the current understanding of its genetic etiology will be reviewed.
KeywordsCongenital Heart Disease Turner Syndrome Bicuspid Aortic Valve Hypoplastic Leave Heart Syndrome Aortic Valve Stenosis
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- 9.Ferencz, C., A. Correa-Villasenor, C. A. Loffredo, and P. D. Wilson. 1997. Left-sided obstructive lesions, p. 166–227, Genetic and Environmental Risk Factors of Major Cardiovascular Malformations: The Baltimore-Washington Infant Study: 1981–1989, vol. 5. Futura Publishing Company, Inc., Armonk.Google Scholar
- 10.Fyler, D. C. 1980. Report of the New England regional infant cardiac program. Pediatrics 65:375–461.Google Scholar
- 12.Greenwood, R. D., A. Rosenthal, L. Parisi, D. C. Fyler, and A. S. Nadas. 1975. Extracardiac abnormalities in infants with congenital heart disease. Pediatrics 55:485–92.Google Scholar
- 21.Perry, L. W., C. A. Neill, C. Ferencz, J. D. Rubin, and C. A. Loffredo. 1993. Infants with congenital heart disease: the cases, p. 33–62.InC. Ferencz, J. D. Rubin, C. A. Loffredo, and C. A. Magee (ed.), Epidemiology of Congenital Heart Disease: The Baltimore-Washingtion Infant Study 1981–1989, vol. 4. Futura Publishing Company, Inc., Mount Kisco.Google Scholar
- 22.Poissonnier, M., M. L. Maroteaux-Chauvet, A. Aurias, and F. Couillard. 1981. [Fatal hypoplasia of the left heart in 2 brothers an reciprocal chromosome translocation (8;11) (p211;p1.53) in their mother: difficulties in genetic counseling]. J Genet Hum 29:297–319.Google Scholar