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Published on: June 19, 2018
Identification of Hypoplastic Left Heart Genotypes and Phenotypes; The Window toward Future Cell-Based Therapy: A
1From the Department of Pediatric Cardiology, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Insights
Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect. Understanding its diverse phenotypes and genetic causes is crucial for developing new molecular treatments to improve outcomes.
Area of Science:
- Cardiology
- Developmental Biology
- Genetics
Background:
- Hypoplastic left heart syndrome (HLHS) is a common and fatal single ventricle anomaly.
- Early prenatal diagnosis can be challenging due to the progressive nature of left heart hypoplasia.
- HLHS is a heterogeneous congenital heart disease with varied phenotypes, complicating treatment strategies.
Purpose of the Study:
- To provide comprehensive information on HLHS phenotypes and genotypes.
- To explore novel molecular strategies for HLHS treatment.
- To highlight the importance of phenotypic determination for identifying etiologic factors and therapeutic approaches.
Main Methods:
- Review of current literature on HLHS phenotypes, genotypes, and molecular mechanisms.
- Analysis of genetic defects and flow-mediated factors contributing to HLHS.
- Discussion of emerging molecular therapeutic strategies based on genetic etiologies.
Main Results:
- HLHS exhibits diverse phenotypes and non-Mendelian genetic origins.
- Genetic defects impact endocardial and cardiomyocyte development, leading to valve and myocardial malformations.
- Current therapeutic goals focus on enhancing right ventricular function and exploring biventricular conversion.
Conclusions:
- Phenotypic and genotypic characterization is fundamental for effective HLHS management.
- Novel molecular therapies targeting genetic causes offer potential for improved treatment.
- Future research aims to establish biventricular physiology in selected HLHS cases.
Abstract:
Hypoplastic left heart syndrome (HLHS) is a prevalent and lethal type of single ventricle anomaly. During early prenatal evaluations, left heart hypoplasia may be neglected due to its progressive features. It is a heterogeneous congenital heart disease with different phenotypes. Currently, there is no definite treatment for HLHS. This is in part due to its heterogeneous phenotypes that require different management. In addition, hindrances in recognizing the etiologic factors do not allow early preventive or therapeutic procedures. Phenotypic determination is fundamental to identifying the etiologic factors and therapeutic strategies. This review article introduces comprehensive information about different phenotypes and genotypes of HLHS and their novel molecular strategy. Genetic defects and flow-mediated mechanisms are the main known factors of HLHS. Recent studies reported additional data about its nonmendelian genetic origins associated with heterogeneous phenotypes. The genetic defects influence endocardium or cardiomyocyte development to yield early or late valve deformities and myocardial malformations. The new molecular therapeutic methods are essentially based on genetic etiologies. The principal therapeutic purpose is reinforcing the function of the right ventricle in patients with nonfunctional left ventricles. The ultimate desire is to create a biventricular heart in selected cases.
