OBJECTIVE: Left ventricular outflow tract obstructive (LVOTO) malformations are a leading cause of infant mortality from birth defects. Genetic mechanisms are likely, and there may be a higher rate of asymptomatic LVOTO anomalies in relatives of affected children. This study sought to define the incidence of cardiac anomalies in first-degree relatives of children with congenital aortic valve stenosis (AVS), coarctation of the aorta (CoA), and hypoplastic left heart syndrome (HLHS). METHODS: A total of 113 probands with a nonsyndromic LVOTO malformation of AVS (n = 25), BAV (n = 3), CoA (n = 52), HLHS (n = 30), and aortic hypoplasia with mitral valve atresia (n = 2) were ascertained through chart review or enrolled at the time of diagnosis. Echocardiography was performed on 282 asymptomatic first-degree relatives. RESULTS: Four studies had poor acoustic windows, leaving 278 studies for analysis. BAV were found in 13 (4.68%) first-degree relatives. The relative risk of BAV in the relatives was 5.05 (95% confidence interval: 2.2-11.7), and the broad sense heritability was 0.49, based on a general population frequency of 0.9%. BAV was more common in multiplex families compared with sporadic cases. An additional 32 relatives had anomalies of the aorta, aortic valve, left ventricle, or mitral valve. CONCLUSIONS: The presence of an LVOTO lesion greatly increases the risk of identifying BAV in a parent or sibling, providing additional support for a complex genetic cause. The parents and siblings of affected patients should be screened by echocardiography as the presence of an asymptomatic BAV may carry a significant long-term health risk.
OBJECTIVE:Left ventricular outflow tract obstructive (LVOTO) malformations are a leading cause of infant mortality from birth defects. Genetic mechanisms are likely, and there may be a higher rate of asymptomatic LVOTO anomalies in relatives of affected children. This study sought to define the incidence of cardiac anomalies in first-degree relatives of children with congenital aortic valve stenosis (AVS), coarctation of the aorta (CoA), and hypoplastic left heart syndrome (HLHS). METHODS: A total of 113 probands with a nonsyndromic LVOTO malformation of AVS (n = 25), BAV (n = 3), CoA (n = 52), HLHS (n = 30), and aortic hypoplasia with mitral valve atresia (n = 2) were ascertained through chart review or enrolled at the time of diagnosis. Echocardiography was performed on 282 asymptomatic first-degree relatives. RESULTS: Four studies had poor acoustic windows, leaving 278 studies for analysis. BAV were found in 13 (4.68%) first-degree relatives. The relative risk of BAV in the relatives was 5.05 (95% confidence interval: 2.2-11.7), and the broad sense heritability was 0.49, based on a general population frequency of 0.9%. BAV was more common in multiplex families compared with sporadic cases. An additional 32 relatives had anomalies of the aorta, aortic valve, left ventricle, or mitral valve. CONCLUSIONS: The presence of an LVOTO lesion greatly increases the risk of identifying BAV in a parent or sibling, providing additional support for a complex genetic cause. The parents and siblings of affected patients should be screened by echocardiography as the presence of an asymptomatic BAV may carry a significant long-term health risk.
Authors: Jay R Hove; Reinhard W Köster; Arian S Forouhar; Gabriel Acevedo-Bolton; Scott E Fraser; Morteza Gharib Journal: Nature Date: 2003-01-09 Impact factor: 49.962
Authors: Kim L McBride; Lisa Marengo; Mark Canfield; Peter Langlois; David Fixler; John W Belmont Journal: Birth Defects Res A Clin Mol Teratol Date: 2005-08
Authors: Siddharth K Prakash; Carolyn A Bondy; Cheryl L Maslen; Michael Silberbach; Angela E Lin; Laura Perrone; Giuseppe Limongelli; Hector I Michelena; Eduardo Bossone; Rodolfo Citro; Scott A Lemaire; Simon C Body; Dianna M Milewicz Journal: Am J Med Genet A Date: 2016-09-08 Impact factor: 2.802
Authors: Kim L McBride; Gloria A Zender; Sara M Fitzgerald-Butt; Daniel Koehler; Andres Menesses-Diaz; Susan Fernbach; Kwanghyuk Lee; Jeffrey A Towbin; Suzanne Leal; John W Belmont Journal: Eur J Hum Genet Date: 2009-01-14 Impact factor: 4.246
Authors: Laura E Mitchell; Jin Long; Jennifer Garbarini; Prasuna Paluru; Elizabeth Goldmuntz Journal: Birth Defects Res A Clin Mol Teratol Date: 2010-01