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Molecular determinants of left and right outflow tract obstruction
1Baylor College of Medicine, Houston, TX 77030, USA. jtowbin@bcm.tmc.edu
Insights
Congenital heart defects, common birth defects, often involve heart obstructions. This review explores the molecular causes of these obstructive disorders, impacting newborn circulation.
Area of Science:
- Cardiology
- Developmental Biology
- Genetics
Background:
- Congenital heart defects (CHDs) are the most frequent birth defects, affecting 0.8-1% of live births.
- CHDs often present as specific morphogenetic defects, compatible with fetal circulation but causing severe symptoms post-delivery.
- Obstructive CHDs can lead to cyanosis or cardiovascular collapse, necessitating timely diagnosis and intervention.
Purpose of the Study:
- To review obstructive disorders of the left and right sides of the heart.
- To discuss the molecular determinants underlying these congenital heart conditions.
- To highlight the association between obstructive CHDs, genetic syndromes, and identified genetic pathways.
Main Methods:
- Literature review focusing on obstructive congenital heart defects.
- Analysis of morphogenetic defects and their impact on cardiac function.
- Examination of genetic associations and molecular pathways involved in CHD development.
Main Results:
- Obstructive CHDs often result in single ventricle physiology due to hypoplastic ventricles.
- Conditions discussed include hypoplastic left heart syndrome, aortic coarctation, pulmonary stenosis, and tetralogy of Fallot.
- Many obstructive CHDs are linked to genetic syndromes with identifiable dysmorphic features.
Conclusions:
- Understanding the molecular basis of obstructive CHDs is crucial for diagnosis and treatment.
- Genetic factors play a significant role in the etiology of many complex congenital heart defects.
- Further research into genetic pathways can elucidate the developmental origins of these conditions.
Abstract:
Congenital heart defects represent the most common group of human birth defects; they occur in 0.8-1% of live births and in 10% of spontaneously aborted fetuses. Heart defects seen in newborns typically represent specific morphogenetic defects of individual chambers or regions of the heart, with the remaining portions of the heart developing relatively normally. These developmental defects are commonly compatible with the intrauterine circulation, where the pulmonary circulation and systemic circulation work in concert, resulting in adequate embryonic growth and development. After delivery, however, significant cardiac symptoms develop. In many of these disorders, cyanosis is the earliest feature, while in others, cardiovascular collapse occurs before diagnosis. In this review, obstruction of the left and right sides of the heart are discussed. In these disorders, ventricular hypoplasia resulting in single ventricle physiologic characteristics is typical. The unaffected ventricle in these cases is usually morphologically and physiologically normal. These conditions include hypoplastic left heart syndrome and aortic coarctation on the left side, pulmonary stenosis, tetralogy of Fallot, and other complex right ventricle obstructive disorders. Many of these disorders occur in association with genetic syndromes identifiable by dysmorphic features. In some cases, the gene(s) has been identified or the genetic pathway has been defined. The purpose of this review is to discuss the molecular determinants of these obstructive disorders.