Considering the Genetic Architecture of Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is among the most severe cardiovascular malformations and understanding its causes is crucial to making progress in prevention and treatment. Genetic analysis is a broadly useful tool for dissecting complex causal mechanisms and it is playing a significant role in HLHS research. However, unlike classical Mendelian disorders where a relatively small number of genes are largely determinative of the occurrence and severity of the disease, the picture in HLHS is complex. De novo single-gene and copy number variant (CNV) disorders make an important contribution, but there is emerging evidence for causal contributions from lower penetrance and common variation. Integrating this emerging knowledge into clinical diagnostics and translating the findings into effective prevention and treatment remain challenges for the future.

Automated summary

Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation and understanding its causes is crucial. Genetic analysis plays a significant role in HLHS research, but its complex etiology involves both single-gene and copy number variant (CNV) disorders, as well as lower penetrance and common variation. Integrating this knowledge into clinical diagnostics and effective prevention and treatment is a challenge for the future.