Hostname: page-component-8448b6f56d-sxzjt Total loading time: 0 Render date: 2024-04-24T12:46:40.165Z Has data issue: false hasContentIssue false
  • English
  • Français

The genetics of hypoplastic left heart syndrome

Published online by Cambridge University Press:  19 August 2008

Paul D. Grossfeld
Paul D. Grossfeld*
Affiliation:
Division of Pediatric Cardiology and Department of Medicine, University of California, San Diego, USA
*
Paul D. Grossfeld, MD, Division of Pediatric Cardiology and Department of Medicine, University of California, San Diego 200 West Arbor Drive San Diego, California 92103, USA. Tel: 619 543 5980; Fax: 619 534 8081; E-maii: PDGMD@aol.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Hypoplastic left heart syndrome is one of the most therapeutically challenging congenital cardiac defects. It accounts for as many as 1.5% of all congenital heart defects, but is responsible for up to one quarter of deaths in neonates with heart disease.1 The management of hypoplastic left heart syndrome is controversial. Two surgical options exist:2,3 the Norwood procedure, is a three stage repair in which the morphologically right ventricle is converted to function as the systemic ventricle. Alternatively, orthotopic transplantation can be performed. Although both surgical options have had improved outcomes, the prognosis for long-term survival is guarded, with a five year survival for either approach reported to be in the region of 50–60%. In this review, I explore the evidence for a genetic etiology for the “classic” hypoplastic left heart syndrome, defined as mitral and/or aortic atresia with hypoplasia of the left ventricular cavity and the other left-sided structures.

Type
Continuing Medical Education
Information
Cardiology in the Young , Volume 9 , Issue 6 , November 1999 , pp. 627 - 632
Copyright
Copyright © Cambridge University Press 1999

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Lang, P, Fyler, DC. Hypoplastic left heart syndrome, mitral atresia and aortic atresia. In: “Nadasi Pediatric Cardiology”, ed. Fyler, Donald C.. Hanley & Belfus, Inc. 1992; 623–634Google Scholar
2.Norwood, WI. Hypoplastic left heart syndrome. Ann Thorac Surg 1991; 52:688–695CrossRefGoogle ScholarPubMed
3.Razzouk, AJ, Chinnock, RE, Gundry, SRJohnston, JK, Larsen, RL, Baum, MF, Mulla, NF, Bailey, LL. Transplantation as a primary treatment for hypoplastic left heart syndrome: Intermediate-term results. Ann Thorac Surg 1996; 62:1–8CrossRefGoogle ScholarPubMed
4.Mair, DD, Titus, JL, Davis, GD, Ritter, DG. Cardiac rhabdomyoma simulating mitral atresia. Chest 1977; 71:102–105CrossRefGoogle ScholarPubMed
5.Watanabe, T, Hojo, Y, Kozaki, T, Nagashima, M, Ando, M. Hypoplastic left heart syndrome with rhabdomyoma of the left ventricle. Pediatr Cardiol 1991; 12:121–122CrossRefGoogle ScholarPubMed
6.Remmell-Dow, DR, Bharati, S, Davis, JT, Lev, M, Allen, HD. Hypoplasia of the eustrachian valve and abnormal orientation of the limbus of the foramen ovale in hypoplastic left heart syndrome. Am Heart J 1995; 130:148–52CrossRefGoogle ScholarPubMed
7.Hajdu, J, Marton, T, Toth-Pal, E, Cesko, I, Hrubi, E, Belics, Z, Papp, Z. Severe left heart developmental disorder and severe fetal arrhythmia in the same family- a coincidental association? Orvosi Hetilap 1998; 139:767–9Google Scholar
8.Cook, A. Personal Communication 1999Google Scholar
9.Fishman, NG, Hog, RV, Rudolph, AM, Heyman, MA. Models of congenital heart disease in fetal lambs. Circulation 1978; 58:354–364CrossRefGoogle ScholarPubMed
10.Harh, JY, Paul, MH, Gallen, WJ, Friedberg, DZ, Kaplan, S. Pediatr Cardiolo Experimental production of hypoplastic left heart syndrome in the chick embryo. Am J Card 1973; 31:51–56CrossRefGoogle Scholar
11.Kojima, H, Ogimi, Y, Mizutani, K, Nishimura, Y. Hypoplastic left heart syndrome in siblings. Lancet 1969; 2:701CrossRefGoogle ScholarPubMed
12.Brownell, LG, Shokeri, MHInheritance of hypoplastic left heart syndrome (HLHS): further observations. Clinical Genetics 1976; 9:245–249CrossRefGoogle ScholarPubMed
13.Grobman, W, Pergament, E. Isolated hypoplastic left heart syndrome in three siblings. Obstetrics and Gynecology 1996; 88:673–5CrossRefGoogle ScholarPubMed
14.Brenner, JI, Berg, KA, Schneider, DS, Clark, EB, Boughman, JA. Cardiac malformation in relatives of infants with hypoplastic left heart syndrome. Am J Dis Child 1989; 143:1492–1494Google ScholarPubMed
15. Left-Sided Obstructive Lesions. In: Perspectives in Pediatric Cardiology Volume 5: Genetic and Environmental Risk Factors of Major Cardiovascular Malformations. The Baltimore-Washington Infant Study 1981–1989. Series Editor: Anderson, RH; Ed: Ferencz, C, Loffredo, CA, Correa-Villasenor, AWilson, PD. Futura Publishing Company, Inc. 1997; 166–227Google Scholar
16.Natowics, M, Chatten, J, Clancy, R, Conrad, K, Glauser, T, Huff, D, Lin, A, Norwood, W, Rorke, LB, Uri, A, Weinberg, P, Zackai, E, Kelly, . RI Genetic disorders and major extracardiac anomalies associated with the hypoplastic left heart syndrome. Pediatrics 1988; 82:698–706CrossRefGoogle Scholar
17.Glauser, TA, Zackai, E, Weinberg, P, Clancy, R. Holt-Oram Syndrome associated with the hypoplastic left heart syndrome. Clinical Genetics 1989 36:69–72CrossRefGoogle ScholarPubMed
18.Li, QY, Newbury-Ecob, RA, Terrett, JA, Wilson, DI, Curtis, AR, Yi, CH, Geburh, T, Bullen, PJ, Robson, SC, Strachan, T, Bonnet, D, Lyonett, S, Young, ID, Raebum, JA, Buckler, AJ, Law, DJ, Brook, JD. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family Nature Genetics 1997; 15:21–29Google Scholar
19.Basson, CT, Bachinsky, DR, Lin, RC, Levi, T, Elkins, JS, Soults, J, Grayzel, D, Kroumpouzou, E, Traill, TA, Leblanc-Staceski, J, Renault, B, Kucherlapati, R, Seidman, JG, Seidman, CE. Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome. Nature Genetics 1997; 15:411CrossRefGoogle ScholarPubMed
20.Thomas, IT, Honore, GM, Jewett, T, Velvis, H, Garber, P, Ruiz, C. Holzgreve syndrome: recurrence in sibs. Am J Med Gene 1993; 45:767–9CrossRefGoogle ScholarPubMed
21.Czarnecki, P, Lacombe, D, Weiss, L. Toriello-Carey syndrome: evidence for X-linked inheritance. Am J Med Gen 1996; 65:291–43.0.CO;2-S>CrossRefGoogle ScholarPubMed
22.Consevage, MW, Seip, JR, Belchis, DA, Davis, AT, Baylen, BG, Rogan, PK. Association of a mosaic chromosomal 22q11 deletion with hypoplastic left heart syndrome. Am J Card 1996; 77:1023–5CrossRefGoogle ScholarPubMed
23.Pinar, H, Carpenter, MW, Abuelo, D, Singer, DB. Fryns syndrome: a new definition. Pediatric Pathology 1994; 14:467–78CrossRefGoogle ScholarPubMed
24.Lehman, CD, Nyberg, Da, Winter, Tc III, Kapur, RP, Restra, RG, Luthy, DA. Trisomy 13 syndrome: prenatal US findings in a review of 33 cases. Radiology 1995; 194:217–22CrossRefGoogle Scholar
25.Van Praagh, S, Truman, T, Firpo, A, Bano-Rodrigo, A, Fried, R, McManus, B. Cardiac malformations in trisomy–18: A study of 41 postmortem cases. J Am Coll Cardiol 1989; 13:1586–97CrossRefGoogle ScholarPubMed
26.Kang, S, Graham, JM Jr, Olney, AH, Biesecker, LG. Gli3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. Nature Genetics 1997; 15:266–8CrossRefGoogle ScholarPubMed
27.Kohler, HG. Brief clinical report: familial neonatally lethal syndrome of hypoplastic left heart, absent pulmonary lobation, polydactyly, and talipes, probably Smith-Lemli-Opitz (RSH) Syndrome. Am J Med Gen 1983; 14:423–8.CrossRefGoogle ScholarPubMed
28.Waterham, HR, Wijburg, FA, Hennekam, RC, Vreken, P, Poll-The, BT, Dorland, L, Duran, M, Jira, PE, Smertink, JA, Wevers, RA, Wanders, RJ. Smith-Lemli-Opitz syndrome is caused by mutations in the 7-dehydrocholesterol reductase gene. Am J Hum Gen 1998; 63:329–38CrossRefGoogle ScholarPubMed
29.Wassif, CA, Maslen, C, Kachilele-Linjewile, S, Lin, D, Linck, LM, Connor, WE. Mutations in the human sterol delta7-reductase gene at 11q12–13 cause Smith-Lemli-Opitz syndrome. Am J Hum Gen 1998; 63:55–62CrossRefGoogle ScholarPubMed
30.Miyiabara, S, Sugihara, H, Maehara, N, Shouno, H, Tasaki, H, Yoshida, K, Saito, N, Kayama, FIbara, SSuzumori, K. Significance of cardiovascular malformations in cystic hygroma: a new interpretation of the pathogenesis. Am J Med Gen 1989; 34:489–501CrossRefGoogle Scholar
31.Jacobsen, P, Hauge, M, Henningsen, K, Hobolth, N, Mikkelsen, M, Phillip, J. An (11;21) translocation in four generations with chromosome 11 abnormalities in the offspring. Human Heredity 1973; 23:568–585CrossRefGoogle Scholar
32.Grossfeld, PD. 1999 Unpublished resultsGoogle Scholar
33.Penny, LA, DelliAquilla, M, Jones, MC, Bergoffen, J, Cunniff, C, Fryns, JP, Grace, E, Graham, JM Jr, Kouseff, B, Mattina, T, Syme, J, Voullaire, L, Zelante, L, Zenger-Hain, J, Jones, OW, Evans, GA. Clinical and molecular characterization of patients with distal 11q deletions. Am J Hum Genet 1995; 56:676–683Google ScholarPubMed
34.Tunnacliffe, A, Jones, C, Le Paslier, D, Todd, RCherif, D, Birdsall, M, Devenish, L, Yousry, C, Cotter, FE, James, MR. Localization of Jacobsen syndrome breakpoints on a 40-Mb physical map of distal chromosome 11q. Genome Research 1999; 9:44–52CrossRefGoogle ScholarPubMed
35.Bockman, DE, Redmond, ME, Waldo, K, Davis, H, Kirby, MI. Effect of neural crest ablation on development of the heart and arch arteries in the chick. 1987 Am J of Anataomy 1987; 180:332–341Google ScholarPubMed
36.Mishibatake, M, Kirby, ML, Van Mierop, LHS. Pathogenesis of persistent truncus arteriosus and dextroposed aorta in the chick embryo after neural crest ablation. Circulation 1987; 75:255–264CrossRefGoogle Scholar
37.Leatherbury, L, Gauldin, HE, Waldo, K, Kirby, ML. Microcinephotography of the developing heart in neural crest-ablated chick embryos. Circulation 1990; 81:1047–1057CrossRefGoogle ScholarPubMed
38.Tomita, H, Connuck, DM, Leatherbury, L, Kirby, ML. Relation of early hemodynamic changes to final cardiac phenotype and survival after neural crest ablation in chick embryos. Circulation 1991; 84:1289–1295CrossRefGoogle ScholarPubMed
39.Kirby, ML and Waldo, KL. Neural crest and cardiovascular patterning. Circ Res. 1995; 77:211–215CrossRefGoogle ScholarPubMed
40.Conway, SJ, Godt, RE, Hatcher, CJ, Leatherbury, L, Zolotouchnikov, VV, Brotto, MA, Copp, AJ, Kirby, ML, Creazzo, TL. Neural crest is involved in development of abnormal myocardial function J Mol Cell Cardiol 1997; 29:2675–2685CrossRefGoogle ScholarPubMed
41.Takamura, KOkishima, T, Ohdo, S, Hayakawa, K. Association of cephalic neural crest cells with cardiovascular development, particularly that of the semilunar valves. Anataomy and Embryology. 1990; 182:263–272Google ScholarPubMed
42.Jones, KL. Smithis Recognizable Patterns of Human Malformation. WB. Saunders Co. 5th edition 1997Google Scholar
43.Kappetein, AP, Gittenberger-de Groot, AC, Zwinderman, AH, Rohmer, J, Poelmann, RE, Huysmanns, HA. The neural crest as a possible pathogenetic factor in coarctation of the aorta and bicuspid aortic valve. J Thorac Cardiovasc Surg 1991 102:830–6CrossRefGoogle ScholarPubMed