Human Genetics of Atrioventricular Septal Defect
Atrioventricular septal defects (AVSD), also known as a common atrioventricular canal (CAVC), are clinically severe heart malformations that affect about 1 out of every 2,100 live births. AVSD is associated with cytogenetic disorders, such as Down syndrom
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Cheryl L. Maslen
Contents 26.1 26.2 26.3
Introduction ................................................................................................................. Disease Model ............................................................................................................. AVSD Genes and Pathways ......................................................................................... 26.3.1 CRELD1 Mutations ........................................................................................ 26.3.2 VEGFA Pathway Gene Mutations ................................................................. 26.3.3 NR2F2 Mutations ........................................................................................... 26.4 Additional Risk Factors ............................................................................................... Conclusion .............................................................................................................................. References ...............................................................................................................................
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Abstract
Atrioventricular septal defects (AVSD), also known as a common atrioventricular canal (CAVC), are clinically severe heart malformations that affect about 1 out of every 2,100 live births. AVSD is associated with cytogenetic disorders, such as Down syndrome and numerous rare genetic syndromes, but also occurs as a simplex trait. Studies in mouse models have identified over 100 genetic mutations that have the potential to cause an AVSD. However, studies in humans indicate that AVSD is genetically heterogeneous and that the cause in humans is very rarely a single-gene defect. Familial cases do occur, usually with autosomal dominant inheritance, and the mutations identified in those families suggest biochemical pathways of interest. In addition, the frequent occurrence of AVSD in some syndromes, such as heterotaxy syndrome, points to additional genes/pathways that increase AVSD risk. Accordingly, while the genetic underpinnings for C.L. Maslen Department of Medicine, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA e-mail: [email protected] © Springer-Verlag Wien 2016 S. Rickert-Sperling et al. (eds.), Congenital Heart Diseases: The Broken Heart: Clinical Features, Human Genetics and Molecular Pathways, DOI 10.1007/978-3-7091-1883-2_26
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C.L. Maslen
most AVSD remain unknown, there have been advances in identifying genetic risk factors for AVSD in both syndromic and nonsyndromic cases. This chapter summarizes the current knowledge of the genetic basis for AVSD.
26.1
Introduction
Atrioventricular septal defects (AVSD) are a group of phenotypically and genetically heterogeneous heart malformations (see Chap. 25). The most commonly occurring genetic association for AVSD is with trisomy 21, which causes Down syndrome. An estimated 65 % of all cases of complete AVSD occur in individuals with Down syndrome.
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